AU2005227365A1 - Novel compounds - Google Patents

Description

P/00/011 Regulation 3.2

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT

(ORIGINAL)

Name of Applicants: Actual Inventors: Address for Service: Invention Title: Glaxo Group Limited, of Glaxo House, Berkeley Avenue, Greenford, Middlesex UB6 ONN, United Kingdom

AND

SmithKline Beecham of New Horizons Court, Brentford, Middlesex TW8 9EP, United Kingdom

AND

SmithKline Beecham Corporation, of One Franklin Plaza, Philadelphia, PA 19103, United States of America Pankaj AGARWAL John P. COGSWELL Ying-Ta LAI Shelby A. MARTENSEN Randall F. SMITH Jay C. STRUM Qing XIE DAVIES COLLISON CAVE, Patent Trademark Attorneys, of 1 Nicholson Street, Melbourne, 3000, Victoria, Australia Ph: 03 9254 2777 Fax: 03 9254 2770 Attorney Code: DM "Novel compounds" The following statement is a full description of this invention, including the best method of performing it known to us:- P:\OPER\MKR\SPECdiv 2001292619.doc-17/10/05 1- O Novel Compounds This is a divisional of Australian patent application No. 2001292619, the entire contents of which are incorporated herein by reference.

lt 5 Field of Invention

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c This invention relates to newly identified polypeptides and polynucleotides encoding such polypeptides, to their use in diagnosis and in identifying compounds that may be agonists, antagonists that are potentially useful in therapy, and to production of such polypeptides and O polynucleotides. The polynucleotides and polypeptides of the present invention also relate to C1 10 proteins with signal sequences which allow them to be secreted extracellularly or membraneassociated (hereinafter often referred collectively as secreted proteins or secreted polypeptides).

Background of the Invention The drug discovery process is currently undergoing a fundamental revolution as it embraces "functional genomics", that is, high throughput genome- or gene-based biology. This approach as a means to identify genes and gene products as therapeutic targets is rapidly superceding earlier approaches based on "positional cloning". A phenotype, that is a biological function or genetic disease, would be identified and this would then be tracked back to the responsible gene, based on its genetic map position.

Functional genomics relies heavily on high-throughput DNA sequencing technologies and the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery.

Proteins and polypeptides that are naturally secreted into blood, lymph and other body fluids, or secreted into the cellular membrane are of primary interest for pharmaceutical research and development. The reason for this interest is the relative ease to target protein therapeutics into their place of action (body fluids or the cellular membrane).

The natural pathway for protein secretion into extracellular space is the endoplasmic reticulum in eukaryotes and the inner membrane in prokaryotes (Palade, 1975, Science, 189, 347; Milstein, Brownlee, Harrison, and Mathews, 1972, Nature New Biol., 239, 117; Blobel, and Dobberstein, 1975, J. Cell. Biol., 67, 835). On the other hand, there is no known natural pathway for exporting a protein from the exterior of the cells into the cytosol (with the exception of pinocytosis, a mechanism of snake venom toxin intrusion into cells).

Therefore targeting protein therapeutics into cells poses extreme difficulties.

The secreted and membrane-associated proteins include but are not limited l to all peptide hormones and their receptors (including but not limited to insulin, O growth hormones, chemokines, cytokines, neuropeptides, integrins, kallikreins, Slamins, melanins, natriuretic hormones, neuropsin, neurotropins, pituitiary 0 hormones, pleiotropins, prostaglandins, secretogranins, selectins, thromboglobulins, 0 5 thymosins), the breast and colon cancer gene products, leptin, the obesity gene protein and its receptors, serum albumin, superoxide dismutase, spliceosome proteins, 7TM (transmembrane) proteins also called as G-protein coupled receptors, I0 immunoglobulins, several families of serine proteinases (including but not limited to proteins of the blood coagulation cascade, digestive enzymes), deoxyribonuclease CN 10 I, etc.

Therapeutics based on secreted or membrane-associated proteins approved by FDA or foreign agencies include but are not limited to insulin, glucagon, growth hormone, chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone, calcitonin, adrenocorticotropic hormone (ACTH), vasopressin, interleukines, interferones, immunoglobulins, lactoferrin (diverse products marketed by several companies), tissue-type plasminogen activator (Alteplase by Genentech), hyaulorindase (Wydase by Wyeth-Ayerst), domase alpha (Pulmozyme\ by Genentech), Chymodiactin (chymopapain by Knoll), alglucerase (Ceredase by Genzyme), streptokinase (Kabikinase by Pharmacia) (Streptase by Astra), etc. This indicates that secreted and membrane-associated proteins have an established, proven history as therapeutic targets. Clearly, there is a need for identification and characterization of further secreted and membrane-associated proteins which can play a role in preventing, ameliorating or correcting dysfunction or disease, including but not limited to diabetes, breast-, prostate-, colon cancer and other malignant tumors, hyper- and hypotension, obesity, bulimia, anorexia, growth abnormalities, asthma, manic depression, dementia, delirium, mental retardation, Huntington's disease, Tourette's syndrome, schizophrenia, growth, mental or sexual development disorders, and dysfunctions of the blood cascade system including those leading to stroke. The proteins of the present invention which include the signal sequences are also useful to further elucidate the mechanism of protein transport which at present is not entirely understood, and thus can be used as research tools.

Summary of the Invention The present invention relates to particular polypeptides and polynucleotides of the genes set forth in Table I, including recombinant materials and methods for their production.

Such polypeptides and polynucleotides are of interest in relation to methods of treatment of certain diseases, including, but not limited to, the diseases set forth in Tables fl and V, hereinafter referred to as "diseases of the invention". In a further aspect, the invention relates to methods for identifying agonists and antagonists inhibitors) using the materials provided by the invention, and treating conditions associated with imbalance of polypeptides and/or polynucleotides of the genes set forth in Table I with the identified compounds. In still a further aspect, the invention relates to diagnostic assays for detecting diseases associated with inappropriate activity or levels the genes set forth in Table I.

Another aspect of the invention concerns a polynucleotide comprising any of the nucleotide sequences set forth in the Sequence Listing and a polypeptide comprising a polypeptide encoded by the nucleotide sequence. In another aspect, the invention relates to a polypeptide comprising any of the polypeptide sequences set forth in the Sequence Listing and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such polypeptides and polynucleotides. Such uses include the treatment of diseases, abnormalities and disorders (hereinafter simply referred to as diseases) caused by abnormal expression, production, function and or metabolism of the genes of this invention, and such diseases are readily apparent by those skilled in the art from the homology.

to other proteins disclosed for each attached sequence. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with the imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate activity or levels of the secreted proteins of the present invention.

Description of the Invention In a first aspect, the present invention relates to polypeptides the genes set forth in Table I. Such polypeptides include: an isolated polypeptide encoded by a polynucleotide comprising a sequence set forth in the Sequence Listing, herein when referring to polynucleotides or polypeptides of the Sequence Listing, a reference is also made to the Sequence Listing referred to in the Sequence Listing; an isolated polypeptide comprising a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; an isolated polypeptide comprising a polypeptide sequence set forth in the Sequence Listing; an isolated polypeptide having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; a polypeptide sequence set forth in the Sequence Listing; and an isolated polypeptide having or comprising a polypeptide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polypeptide sequence set forth in the Sequence Listing; fragments and variants of such polypeptides in to Polypeptides of the present invention are believed to be members of the gene families set forth in Table I They are therefore of therapeutic and diagnostic interest for the reasons set forth in Tables I and V. The biological properties of the polypeptides and polynucleotides of the genes set forth in Table I are hereinafter referred to as "the biological activity" of polypeptides and polynucleotides of the genes set forth in Table I. Preferably, a polypeptide of the present invention exhibits at least one biological activity of the genes set forth in Table I.

Polypeptides of the present invention also include variants of the aforementioned polypeptides, including all allelic forms and splice variants. Such polypeptides vary from the reference polypeptide by insertions, deletions, and substitutions that may be conservative or non-conservative, or any combination thereof. Particularly preferred variants are those in which several, for instance from 50 to 30, from 30 to 20, from 20 to from 10 to 5, from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acids are inserted, substituted, or deleted, in any combination.

Preferred fragments of polypeptides of the present invention include an isolated polypeptide comprising an amino acid sequence having at least 30, 50 or 100 contiguous amino acids from an amino acid sequence set forth in the Sequence Listing, or an isolated polypeptide comprising an amino acid sequence having at least 30, 50 or 100 contiguous amino acids truncated or deleted from an amino acid sequence set forth in the Sequence Listing. Preferred fragments are biologically active fragments that mediate the biological activity of polypeptides and polynucleotides of the genes set forth in Table I, including those with a similar activity or an improved activity, or with a decreased undesirable activity. Also preferred are those fragments that are antigenic or immunogenic in an animal, especially in a human.

Fragments of a polypeptide of the invention may be employed for producing the corresponding full-length polypeptide by peptide synthesis; therefore, these variants may be employed as intermediates for producing the full-length polypeptides of the invention. A polypeptide of the present invention may be in the form of the "mature" protein or may be a t part of a larger protein such as a precursor or a fusion protein. It is often advantageous to Sinclude an additional amino acid sequence that contains secretory or leader sequences, prosequences, sequences that aid in purification, for instance multiple histidine residues, or an 0 additional sequence for stability during recombinant production.

I 5 Polypeptides of the present invention can be prepared in any suitable manner, for instance by isolation form naturally occurring sources, from genetically engineered host cells comprising expression systems (vide infra) or by chemical synthesis, using for instance ND automated peptide synthesizers, or a combination of such methods. Means for preparing such polypeptides are well understood in the art.

In a further aspect, the present invention relates to polynucleotides of the genes set forth in STable I. Such polynucleotides include: C an isolated polynucleotide comprising a polynucleotide sequence having at least 96%, 97%, 98%, or 99% identity to a polynucleotide sequence set forth in the Sequence Listing; an isolated polynucleotide comprising a polynucleotide set forth in the Sequence Listing; an isolated polynucleotide having at least 95%, 96%, 97%, 98%, or 99% identity to a polynucleotide set forth in the Sequence Listing; an isolated polynucleotide set forth in the Sequence Listing; an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide set forth in the Sequence Listing; an isolated polynucleotide having a polynucleotide sequence encoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; an isolated polynucleotide encoding a polypeptide set forth in the Sequence Listing; an isolated polynucleotide having or comprising a polynucleotide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polynucleotide sequence set forth in the Sequence Listing; an isolated polynucleotide having or comprising a polynucleotide sequence encoding a polypeptide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polypeptide sequence set forth in the Sequence Listing; and polynucleotides that are fragments and variants of the above mentioned polynucleotides or that are complementary to above mentioned polynucleotides, over the entire length thereof.

Preferred fragments of polynucleotides of the present invention include an isolated polynucleotide comprising an nucleotide sequence having at least 15, 30, 50 or 100 contiguous nucleotides from a sequence set forth in the Sequence Listing, or an isolated polynucleotide comprising a sequence having at least 30, 50 or 100 contiguous nucleotides truncated or deleted from a sequence set forth in the Sequence Listing.

Preferred variants of polynucleotides of the present invention include splice variants, allelic variants, and polymorphisms, including polynucleotides having one or more single nucleotide polymorphisms (SNPs).

Polynucleotides of the present invention also include polynucleotides encoding polypeptide variants that comprise an amino acid sequence set forth in the Sequence Listing and in which several, for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acid residues are substituted, deleted or added, in any combination.

In a further aspect, the present invention provides polynucleotides that are RNA transcripts of the DNA sequences of the present invention. Accordingly, there is provided an RNA polynucleotide that: comprises an RNA transcript of the DNA sequence encoding a polypeptide set forth in the Sequence Listing; is a RNA transcript of a DNA sequence encoding a polypeptide set forth in the Sequence Listing; comprises an RNA transcript of a DNA sequence set forth in the Sequence Listing; or is a RNA transcript of a DNA sequence set forth in the Sequence Listing; and RNA polynucleotides that are complementary thereto.

The polynucleotide sequences set forth in the Sequence Listing show homology with the polynucleotide sequences set forth in Table IL A polynucleotide sequence set forth in the Sequence Listing is a cDNA sequence that encodes a polypeptide set forth in the Sequence Listing. A polynucleotide sequence encoding a polypeptide set forth in the Sequence Listing may be identical to a polypeptide encoding a sequence set forth in the Sequence Listing or it may be a sequence other than a sequence set forth in the Sequence Listing, which, as a result of the redundancy (degeneracy) of the genetic code, also encodes a polypeptide set forth in the Sequence Listing. A polypeptide of a sequence set forth in the Sequence Listingis related to other proteins of the gene families set forth in Table I, having homology and/or structural similarity with the polypeptides set forth in Table II. Preferred Spolypeptides and polynucleotides of the present invention are expected to have, inter alia, similar biological functions/properties to their homologous polypeptides and O polynucleotides. Furthermore, preferred polypeptides and polynucleotides of the present NO 5 invention have at least one activity of the genes set- forth in Table I.

Polynucleotides of the present invention may be obtained using standard cloning In and screening techniques from a cDNA library derived from mRNA from the tissues set -NO forth in Table IV (see for instance, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)).

10 Polynucleotides of the invention can also be obtained from natural sources such as genomic 0 DNA libraries or can be synthesized using well known and commercially available C, techniques.

When polynucleotides of the present invention are used for the recombinant production of polypeptides of the present invention, the polynucleotide may include the coding sequence for the mature polypeptide, by itself, or the coding sequence for the mature polypeptide in reading frame with other coding sequences, such as those encoding a leader or secretory sequence, a pre-, or pro- or prepro- protein sequence, or other fusion peptide portions. For example, a marker sequence that facilitates purification of the fused polypeptide can be encoded. In certain preferred embodiments of this aspect of the invention, the marker sequence is a hexa-histidine peptide, as provided in the pQE vector (Qiagen, Inc.) and described in Gentz etal., Proc Natl Acad Sci USA (1989) 86:821-824, or is an HA tag. A polynucleotide may also contain non-coding 5' and 3' sequences, such as transcribed, non-translated sequences, splicing and polyadenylation signals, ribosome binding sites and sequences that stabilize mRNA.

Polynucleotides that are identical, or have sufficient identity to a polynucleotide sequence set forth in the Sequence Listing, may be used as hybridization probes for cDNA and genomic DNA or as primers for a nucleic acid amplification reaction (for instance, PCR). Such probes and primers may be used to isolate full-length cDNAs and genomic clones encoding polypeptides of the present invention and to isolate cDNA and genomic clones of other genes (including genes encoding paralogs from human sources and orthologs and paralogs from other species) that have a high sequence similarity to sequences set forth in the Sequence Listing, typically at least 95% identity. Preferred probes and primers will generally comprise at least 15 nucleotides, preferably, at least 30 nucleotides and may have at least 50, if not at least 100 nucleotides. Particularly preferred probes will have between and 50 nucleotides. Particularly preferred primers will have between 20 and Snucleotides.

SA polynucleotide encoding a polypeptide of the present invention, including O homologs from other species, may be obtained by a process comprising the steps of O 5 screening a library under stringent hybridization conditions with a labeled probe having a sequence set forth in the Sequence Listing or a fragment thereof, preferably of at least I nucleotides; and isolating full-length cDNA and genomic clones containing the

NO

Spolynucleotide sequence set forth in the Sequence Listing. Such hybridization techniques C' are well known to the skilled artisan. Preferred stringent hybridization conditions include overnight incubation at 42 0 C in a solution comprising: 50% formamide, 5xSSC (150mM 8 NaCI, 15mM trisodium citrate), 50 mM sodium phosphate (pH 5x Denhardt's solution, c 10 dextran sulfate, and 20 microgram/ml denatured, sheared salmon sperm DNA; followed by washing the filters in 0.1x SSC at about 650C. Thus the present invention also includes isolated polynucleotides, preferably with a nucleotide sequence of at least 100, obtained by screening a library under stringent hybridization conditions with a labeled probe having the sequence set forth in the Sequence Listing or a fragment thereof, preferably of at least 15 nucleotides.

The skilled artisan will appreciate that, in many cases, an isolated cDNA sequence will be incomplete, in that the region coding for the polypeptide does not extend all the way through to the 5' terminus. This is a consequence of reverse transcriptase, an enzyme with inherently low "processivity" (a measure of the ability of the enzyme to remain attached to the template during the polymerisation reaction), failing to complete a DNA copy of the mRNA template during first strand cDNA synthesis.

There are several methods available and well known to those skilled in the art to obtain full-length cDNAs, or extend short cDNAs, for example those based on the method of Rapid Amplification of cDNA ends (RACE) (see, for example, Frohman et al., Proc Nat Acad Sci USA 85, 8998-9002, 1988). Recent modifications of the technique, exemplified by the Marathon (trade mark) technology (Clontech Laboratories Inc.) for example, have significantly simplified the search for longer cDNAs. In the Marathon (trade mark) technology, cDNAs have been prepared from mRNA extracted from a chosen tissue and an 'adaptor' sequence ligated onto each end. Nucleic acid amplification (PCR) is then carried out to amplify the "missing" 5'end of the cDNA using a combination of gene specific and adaptor specific oligonucleotide primers. The PCR reaction is then repeated using 'nested' primers, that is, primers designed to anneal within the amplified product (typically an adapter specific primer that anneals further 3'in the adaptor sequence and a gene specific 8 primer that anneals further 5'in the known gene sequence). The products of this reaction can then be analyzed by DNA sequencing and a full-length cDNA constructed either by joining the product directly to the existing cDNA to give a complete sequence, or carrying out a separate full-length PCR using the new sequence information for the design of the primer.

Recombinant polypeptides of the present invention may be prepared by processes well known in the art from genetically engineered host cells comprising expression systems.

Accordingly, in a further aspect, the present invention relates to expression systems comprising a polynucleotide or polynucleotides of the present invention, to host cells which are genetically engineered with such expression systems and to the production of polypeptides of the invention by recombinant techniques. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention.

For recombinant production, host cells can be genetically engineered to incorporate expression systems or portions thereof for polynucleotides of the present invention.

Polynucleotides may be introduced into host cells by methods described in many standard laboratory manuals, such as Davis et al., Basic Methods in Molecular Biology (1986) and Sambrook et al.(ibid). Preferred methods of introducing polynucleotides into host cells include, for instance, calcium phosphate transfection, DEAE-dextran mediated transfection, transvection, micro-injection, cationic lipid-mediated transfection, electroporation, transduction, scrape loading, ballistic introduction or infection.

Representative examples of appropriate hosts include bacterial cells, such as Streptococci, Staphylococci, E. coli, Streptomyces and Bacillus subtilis cells; fungal cells, such as yeast cells and Aspergillus cells; insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS, HeLa, C127, 3T3, BHK, HEK 293 and Bowes melanoma cells; and plant cells.

A great variety of expression systems can be used, for instance, chromosomal, episomal and virus-derived systems, vectors derived from bacterial plasmids, from bacteriophage, from transposons, from yeast episomes, from insertion elements, from yeast chromosomal elements, from viruses such as baculoviruses, papova viruses, such as vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabies viruses and retroviruses, and vectors derived from combinations thereof, such as those derived from plasmid and bacteriophage genetic elements, such as cosmids and phagemids. The expression systems may contain control regions that regulate as well as engender expression. Generally, any system or vector that is able to maintain, propagate or express a polynucleotide to produce a V polypeptide in a host may be used. The appropriate polynucleotide sequence may be

O

O inserted into an expression system by any of a variety of well-known and routine Stechniques, such as, for example, those set forth in Sambrook et al., (ibid). Appropriate O secretion signals may be incorporated into the desired polypeptide to allow secretion of the O 5 translated protein into the lumen of the endoplasmic reticulum, the periplasmic space or the extracellular environment. These signals may be endogenous to the polypeptide or they may be heterologous signals.

N0 If a polypeptide of the present invention is to be expressed for use in screening Sassays, it is generally preferred that the polypeptide be produced at the surface of the cell.

C 10 In this event, the cells may be harvested prior to use in the screening assay. If the 0polypeptide is secreted into the medium, the medium can be recovered in order to recover C' and purify the polypeptide. If produced intracellularly, the cells must first be lysed before the polypeptide is recovered.

Polypeptides of the present invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Most preferably, high performance liquid chromatography is employed for purification. Well known techniques for refolding proteins may be employed to regenerate active conformation when the polypeptide is denatured during intracellular synthesis, isolation and/or purification.

Polynucleotides of the present invention may be used as diagnostic reagents, through detecting mutations in the associated gene. Detection of a mutated form of a gene is characterized by the polynucleotides set forth in the Sequence Listing in the cDNA or genomic sequence and which is associated with a dysfunction. Will provide a diagnostic tool that can add to, or define, a diagnosis of a disease, or susceptibility to a disease, which results from under-expression, over-expression or altered spatial or temporal expression of the gene. Individuals carrying mutations in the gene may be detected at the DNA level by a variety of techniques well known in the art.

Nucleic acids for diagnosis may be obtained from a subject's cells, such as from blood, urine, saliva, tissue biopsy or autopsy material. The genomic DNA may be used directly for detection or it may be amplified enzymatically by using PCR, preferably RT- PCR, or other amplification techniques prior to analysis. RNA or cDNA may also be used in similar fashion. Deletions and insertions can be detected by a change in size of the amplified product in comparison to the normal genotype. Point mutations can be identified by hybridizing amplified DNA to labeled nucleotide sequences of the genes set forth in Table I. Perfectly matched sequences can be distinguished from mismatched duplexes by RNase digestion or by differences in melting temperatures. DNA sequence difference may also be detected by alterations in the electrophoretic mobility of DNA fragments in gels, with or without denaturing agents, or by direct DNA sequencing (see, for instance, Myers et al., Science (1985) 230:1242). Sequence changes at specific locations may also be revealed by nuclease protection assays, such as RNase and S protection or the chemical cleavage method (see Cotton etal., Proc Nati Acad Sci USA (1985) 85: 4397-4401).

An array of oligonucleotides probes comprising polynucleotide sequences or fragments thereof of the genes set forth in Table I can be constructed to conduct efficient screening of genetic mutations. Such arrays are preferably high density arrays or grids.

Array technology methods are well known and have general applicability and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability, see, for example, M. Chee et al., Science, 274, 610-613 (1996) and other references cited therein.

Detection of abnormally decreased or increased levels of polypeptide or mRNA expression may also be used for diagnosing or determining susceptibility of a subject to a disease of the invention. Decreased or increased expression can be measured at the RNA level using any of the methods well known in the art for the quantitation of polynucleotides, such as, for example, nucleic acid amplification, for instance PCR, RT-PCR, RNase protection, Northern blotting and other hybridization methods. Assay techniques that can be used to determine levels of a protein, such as a polypeptide of the present invention, in a sample derived from a host are well-known to those of skill in the art. Such assay methods include radio-immunoassays, competitive-binding assays, Western Blot analysis and ELISA assays.

Thus in another aspect, the present invention relates to a diagnostic kit comprising: a polynucleotide of the present invention, preferably the nucleotide sequence set forth in the Sequence Listing, or a fragment or an RNA transcript thereof; a nucleotide sequence complementary to that of a polypeptide of the present invention, preferably the polypeptide set forth in the Sequence Listing or a fragment thereof; or an antibody to a polypeptide of the present invention, preferably to the polypeptide set forth in the Sequence Listing.

It will be appreciated that in any sudh'kit, or may comprise a substantial component. Such a kit will be of use in diagnosing a disease or susceptibility to a disease, particularly diseases of the invention, amongst others.

The polynucleotide sequences of the present invention are valuable for chromosome 0 localisation studies. The sequences set forth in the Sequence Listing are specifically targeted to, and can hybridize with, a particular location on an individual human O chromosome. The mapping of relevant sequences to chromosomes according to the present IN 5 invention is an important first step in correlating those sequences with gene associated disease. Once a sequence has been mapped to a precise chromosomal location, the physical Iposition of the sequence on the chromosome can be correlated with genetic map data. Such data are found in, for example, V. McKusick, Mendelian Inheritance in Man (available online through Johns Hopkins University Welch Medical Library). The relationship between genes and diseases that have been mapped to the same chromosomal region are then O identified through linkage analysis (co-inheritance of physically adjacent genes). Precise Shuman chromosomal localisations for a genomic sequence (gene fragment etc.) can be determined using Radiation Hybrid (RH) Mapping (Walter, M. Spillett, Thomas, P., Weissenbach, and Goodfellow, (1994) A method for constructing radiation hybrid maps of whole genomes, Nature Genetics 7, 22-28). A number of RH panels are available from Research Genetics (Huntsville, AL, USA) e.g. the GeneBridge4 RH panel (Hum Mol Genet 1996 Mar,5(3):339-46 A radiation hybrid map of the human genome. Gyapay G, Schmitt K, Fizames C, Jones H, Vega-Czarny N, Spillett D, Muselet D, Prud'Homme JF, Dib C, Auffray C, Morissette J, Weissenbach J, Goodfellow PN). To determine the chromosomal location of a gene using this panel, 93 PCRs are performed using primers designed from the gene of interest on RH DNAs. Each of these DNAs contains random human genomic fragments maintained in a hamster background (human hamster hybrid cell lines). These PCRs result in 93 scores indicating the presence or absence of the PCR product of the gene of interest. These scores are compared with scores created using PCR products from genomic sequences of known location. This comparison is conducted at http://www.genome.wi.mit.edu/.

The polynucleotide sequences of the present invention are also valuable tools for tissue expression studies. Such studies allow the determination of expression patterns of polynucleotides of the present invention which may give an indication as to the expression patterns of the encoded polypeptides in tissues, by detecting the mRNAs that encode them.

The techniques used are well known in the art and include in situ hydridization techniques to clones arrayed on a grid, such as cDNA microarray hybridization (Schena et al, Science, 270, 467-470, 1995 and Shalon et al, Genome Res, 6, 639-645, 1996) and nucleotide amplification techniques such as PCR. A preferred method uses the TAQMAN (Trade mark) technology available from Perkin Elmer. Results from these studies can provide an indication of the normal function of the polypeptide in the organism. In addition, Scomparative studies of the normal expression pattern of mRNAs with that of mRNAs encoded by an alternative form of the same gene (for example, one having an alteration in O polypeptide coding potential or a regulatory mutation) can provide valuable insights into the I 5 role of the polypeptides of the present invention, or that of inappropriate expression thereof in disease. Such inappropriate expression may be of a temporal, spatial or simply t quantitative nature.

N A further aspect of the present invention relates to antibodies. The polypeptides of the invention or their fragments, or cells expressing them, can be used as immunogens to produce antibodies that are immunospecific for polypeptides of the present invention. The Sterm "immunospecific" means that the antibodies have substantially greater affinity for the Spolypeptides of the invention than their affinity for other related polypeptides in the prior art.

Antibodies generated against polypeptides of the present invention may be obtained by administering the polypeptides or epitope-bearing fragments, or cells to an animal, preferably a non-human animal, using routine protocols. For preparation of monoclonal antibodies, any technique which provides antibodies produced by continuous cell line cultures can be used. Examples include the hybridoma technique (Kohler, G. and Milstein, Nature (1975) 256:495-497), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., Immunology Today (1983) 4:72) and the EBV-hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, 77-96, Alan R. Liss, Inc., 1985).

Techniques for the production of single chain antibodies, such as those described in U.S. Patent No. 4,946,778, can also be adapted to produce single chain antibodies to polypeptides of this invention. Also, transgenic mice, or other organisms, including other mammals, may be used to express humanized antibodies.

The above-described antibodies may be employed to isolate or to identify clones expressing the polypeptide or to purify the polypeptides by affinity chromatography.

Antibodies against polypeptides of the present invention may also be employed to treat diseases of the invention, amongst others.

Polypeptides and polynucleotides of the present invention may also be used as vaccines. Accordingly, in a further aspect, the present invention relates to a method for A inducing an immunological response in a mammal that comprises inoculating the mammal with a polypeptide of the present invention, adequate to produce antibody and/or T cell immune response, including, for example, cytokine-producing T cells or cytotoxic T cells, to protect said animal from disease, whether that disease is already established within the O individual or not. An immunological response in a mammal may also be induced by a Smethod comprises delivering a polypeptide of the present invention via a vector directing O expression of the polynucleotide and coding for the polypeptide in vivo in order to induce O 5 such an immunological response to produce antibody to protect said animal from diseases of the invention. One way of administering the vector is by accelerating it into the desired Scells as a coating on particles or otherwise. Such nucleic acid vector may comprise DNA, RNA, a modified nucleic acid, or a DNA/RNA hybrid. For use a vaccine, a polypeptide or a nucleic acid vector will be normally provided as a vaccine formulation (composition). The 10 formulation may further comprise a suitable carrier. Since a polypeptide may be broken O down in the stomach, it is preferably administered parenterally (for instance, subcutaneous, C intra-muscular, intravenous, or intra-dermal injection). Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions that may contain anti-oxidants, buffers, bacteriostats and solutes that render the formulation instonic with the blood of the recipient; and aqueous and non-aqueous sterile suspensions that may include suspending agents or thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampoules and vials and may be stored in a freeze-dried condition requiring only the addition of the sterile liquid carrier immediately prior to use. The vaccine formulation may also include adjuvant systems for enhancing the immunogenicity of the formulation, such as oil-in water systems and other systems known in the art. The dosage will depend on the specific activity of the vaccine and can be readily determined by routine experimentation.

Polypeptides of the present invention have one or more biological functions that are of relevance in one or more disease states, in particular the diseases of the invention hereinbefore mentioned. It is therefore useful to identify compounds that stimulate or inhibit the function or level of the polypeptide. Accordingly, in a further aspect, the present invention provides for a method of screening compounds to identify those that stimulate or inhibit the function or level of the polypeptide. Such methods identify agonists or antagonists that may be employed for therapeutic and prophylactic purposes for such diseases of the invention as hereinbefore mentioned. Compounds may be identified from a variety of sources, for example, cells, cell-free preparations, chemical libraries, collections of chemical compounds, and natural product mixtures. Such agonists or antagonists soidentified may be natural or modified substrates, ligands, receptors, enzymes, etc., as the case may be, of the polypeptide; a structural or functional mimetic thereof (see Coligan et Current Protocols in Immunology l(2):Chapter 5 (1991)) or a small molecule. Such small molecules preferably have a molecular weight below 2,000 daltons, more preferably between 300 and 1,000 daltons, and most preferably between 400 and 700 daltons. It is preferred that these small molecules are organic molecules.

The screening method may simply measure the binding of a candidate compound to the polypeptide, or to cells or membranes bearing the polypeptide, or a fusion protein thereof, by means of a label directly or indirectly associated with the candidate compound.

Alternatively, the screening method may involve measuring or detecting (qualitatively or quantitatively) the competitive binding of a candidate compound to the polypeptide against a labeled competitor agonist or antagonist). Further, these screening methods may test whether the candidate compound results in a signal generated by activation or inhibition of the polypeptide, using detection systems appropriate to the cells bearing the polypeptide.

Inhibitors of activation are generally assayed in the presence of a known agonist and the effect on activation by the agonist by the presence of the candidate compound is observed.

Further, the screening methods may simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide of the present invention, to form a mixture, measuring an activity of the genes set forth in Table I in the mixture, and comparing activity of the mixture of the genes set forth in Table I to a control mixture which contains no candidate compound.

Polypeptides of the present invention may be employed in conventional low capacity screening methods and also in high-throughput screening (HTS) formats. Such HTS formats include not only the well-established use of 96- and, more recently, 384-well micotiter plates but also emerging methods such as the nanowell method described by Schullek et al, Anal Biochem., 246, 20-29, (1997).

Fusion proteins, such as those made from Fc portion and polypeptide of the genes set forth in Table I, as hereinbefore described, can also be used for high-throughput screening assays to identify antagonists for the polypeptide of the present invention (see D. Bennett et al., J Mol Recognition, 8:52-58 (1995); and K. Johanson et al., J Biol Chem, 270(16):9459-9471 (1995)).

The polynucleotides, polypeptides and antibodies to the polypeptide of the present invention may also be used to configure screening methods for detecting the effect of added compounds on the production of mRNA and polypeptide in cells. For example, an ELISA assay may be constructed for measuring secreted or cell associated levels of polypeptide using monoclonal and polyclonal antibodies by standard methods known in the art. This can be used to discover agents that may inhibit or enhance the production of polypeptide (also called antagonist or agonist, respectively) from suitably manipulated cells or tissues.

T

A polypeptide of the present invention may be used to identify membrane bound or Ssoluble receptors, if any, through standard receptor binding techniques known in the art.

SThese include, but are not limited to, ligand binding and crosslinking assays in which the O polypeptide is labeled with a radioactive isotope (for instance, 1251), chemically modified N) 5 (for instance, biotinylated), or fused to a peptide sequence suitable for detection or purification, and incubated with a source of the putative receptor (cells, cell membranes, cell tn supematants, tissue extracts, bodily fluids). Other methods include biophysical techniques such as surface plasmon resonance and spectroscopy. These screening methods may also be used to identify agonists and antagonists of the polypeptide that compete with the binding of the polypeptide to its receptors, if any. Standard methods for conducting such assays are Swell understood in the art.

C

Examples of antagonists of polypeptides of the present invention include antibodies or, in some cases, oligonucleotides or proteins that are closely related to the ligands, substrates, receptors, enzymes, etc., as the case may be, of the polypeptide, a fragment of the ligands, substrates, receptors, enzymes, etc.; or a small molecule that bind to the polypeptide of the present invention but do not elicit a response, so that the activity of the polypeptide is prevented.

Screening methods may also involve the use of transgenic technology and the genes set forth in Table I. The art of constructing transgenic animals is well established. For example, the genes set forth in Table I may be introduced through microinjection into the male pronucleus of fertilized oocytes, retroviral transfer into pre- or post-implantation embryos, or injection of genetically modified, such as by electroporation, embryonic stem cells into host blastocysts. Particularly useful transgenic animals are so-called "knock-in" animals in which an animal gene is replaced by the human equivalent within the genome of that animal. Knock-in transgenic animals are useful in the drug discovery process, for target validation, where the compound is specific for the human target. Other useful transgenic animals are so-called "knock-out" animals in which the expression of the animal ortholog of a polypeptide of the present invention and encoded by an endogenous DNA sequence in a cell is partially or completely annulled. The gene knock-out may be targeted to specific cells or tissues, may occur only in certain cells or tissues as a consequence of the limitations of the technology, or may occur in all, or substantially all, cells in the animal. Transgenic animal technology also offers a whole animal expression-cloning system in which introduced genes are expressed to give large amounts of polypeptides of the present invention Screening kits for use in the above described methods form a further aspect of the Spresent invention. Such screening kits comprise: o a polypeptide of the present invention; O a recombinant cell expressing a polypeptide of the present invention; 5 a cell membrane expressing a polypeptide of the present invention; or an antibody to a polypeptide of the present invention; which polypeptide is preferably that set forth in the Sequence Listing.

\0 C It will be appreciated that in any such kit, or may comprise a C substantial component.

t Glossary The following definitions are provided to facilitate understanding of certain terms used frequently hereinbefore.

"Antibodies" as used herein includes polyclonal and monoclonal antibodies, chimeric, single chain, and humanized antibodies, as well as Fab fragments, including the products of an Fab or other immunoglobulin expression library.

"Isolated" means altered "by the hand of man" from its natural state, if it occurs in nature, it has been changed or removed from its original environment, or both. For example, a polynucleotide or a polypeptide naturally present in a living organism is not "isolated," but the same polynucleotide or polypeptide separated from the coexisting materials of its natural state is "isolated", as the term is employed herein. Moreover, a polynucleotide or polypeptide that is introduced into an organism by transformation, genetic manipulation or by any other recombinant method is "isolated" even if it is still present in said organism, which organism may be living or non-living.

"Secreted protein activity or secreted polypeptide activity" or "biological activity of the secreted protein or secreted polypeptide" refers to the metabolic or physiologic function of said secreted protein including similar activities or improved activities or these activities with decreased undesirable side-effects. Also included are antigenic and immunogenic activities of said secreted protein.

"Secreted protein gene" refers to a polynucleotide comprising any of the attached nucleotide sequences or allelic variants thereof and/or their complements.

"Polynucleotide" generally refers to any polyribonucleotide (RNA) or polydeoxribonucleotide (DNA), which may be unmodified or modified RNA or DNA.

"Polynucleotides" include, without limitation, single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and 0 RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising SDNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture O of single- and double-stranded regions. In addition, "polynucleotide" refers to triplestranded regions comprising RNA or DNA or both RNA and DNA. The term "polynucleotide" also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. "Modified" Sbases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications may be made to DNA and RNA; thus, "polynucleotide" embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in Snature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells.

C "Polynucleotide" also embraces relatively short polynucleotides, often referred to as oligonucleotides.

"Polypeptide" refers to any polypeptide comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds, peptide isosteres.

"Polypeptide" refers to both short chains, commonly referred to as peptides, oligopeptides or oligomers, and to longer chains, generally referred to as proteins. Polypeptides may contain amino acids other than the 20 gene-encoded amino acids. "Polypeptides" include amino acid sequences modified either by natural processes, such as post-translational processing, or by chemical modification techniques that are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications may occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present to the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched and branched cyclic polypeptides may result from post-translation natural processes or may be made by synthetic methods. Modifications include acetylation, acylation, ADPribosylation, amidation, biotinylation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, crosslinking, cyclization, disulfide bond formation, demethylation, formationof covalent crosslinks, formation of cystine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, Smyristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, N racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to a proteins such as arginylation, and ubiquitination (see, for instance, Proteins Structure and O Molecular Properties, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York,

ID

5 1993; Wold, Post-translational Protein Modifications: Perspectives and Prospects, 1-12, in Post-translational Covalent Modification of Proteins, B. C. Johnson, Ed., Academic Press, tI New York, 1983; Seifter et al., "Analysis for protein modifications and nonprotein c cofactors", Meth Enzymol, 182, 626-646, 1990, and Rattan et aL, "Protein Synthesis: Post- C translational Modifications and Aging", Ann NY Acad Sci, 663, 48-62, 1992).

I 10 "Fragment" of a polypeptide sequence refers to a polypeptide sequence that is shorter than the reference sequence but that retains essentially the same biological function or activity as the reference polypeptide. "Fragment" of a polynucleotide sequence refers to a polynucleotide sequence that is shorter than the reference sequence set forth in the Sequence Listing.

"Variant" refers to a polynucleotide or polypeptide that differs from a reference polynucleotide or polypeptide, but retains the essential properties thereof. A typical variant of a polynucleotide differs in nucleotide sequence from the reference polynucleotide.

Changes in the nucleotide sequence of the variant may or may not alter the amino acid sequence of a polypeptide encoded by the reference polynucleotide. Nucleotide changes may result in amino acid substitutions, additions, deletions, fusions and truncations in the polypeptide encoded by the reference sequence, as discussed below. A typical variant of a polypeptide differs in amino acid sequence from the reference polypeptide. Generally, alterations are limited so that the sequences of the reference polypeptide and the variant are closely similar overall and, in many regions, identical. A variant and reference polypeptide may differ in amino acid sequence by one or more substitutions, insertions, deletions in any combination. A substituted or inserted amino acid residue may or may not be one encoded by the genetic code. Typical conservative substitutions include Gly, Ala; Val, Ile, Leu; Asp, Glu; Asn, Gin; Ser, Thr; Lys, Arg; and Phe and Tyr. A variant of a polynucleotide or polypeptide may be naturally occurring such as an allele, or it may be a variant that is not known to occur naturally. Non-naturally occurring variants of polynucleotides and polypeptides may be made by mutagenesis techniques or by direct synthesis. Also included as variants are polypeptides having one or more post-translational modifications, for instance glycosylation, phosphorylaiion, methylation, ADP ribosylation and the like.

Embodiments include methylation of the N-terminal amino acid, phosphorylations of serines and threonines and modification of C-terminal glycines.

"Allele" refers to one of two or more alternative forms of a gene occurring at a given locus in the genome.

S"Polymorphism" refers to a variation in nucleotide sequence (and encoded O polypeptide sequence, if relevant) at a given position in the genome within a population.

5 "Single Nucleotide Polymorphism" (SNP) refers to the occurrence of nucleotide variability at a single nucleotide position in the genome, within a population. An SNP may tIn occur within a gene or within intergenic regions of the genome. SNPs can be assayed using Cc Allele Specific Amplification (ASA). For the process at least 3 primers are required. A common primer is used in reverse complement to the polymorphism being assayed. This common primer can be between 50 and 1500 bps from the polymorphic base. The other two (or more) primers are identical to each other except that the final 3'base wobbles to match

C

1 one of the two (or more) alleles that make up the polymorphism. Two (or more) PCR reactions are then conducted on sample DNA, each using the common primer and one of the Allele Specific Primers.

"Splice Variant" as used herein refers to cDNA molecules produced from RNA molecules initially transcribed from the same genomic DNA sequence but which have undergone alternative RNA splicing. Alternative RNA splicing occurs when a primary RNA transcript undergoes splicing, generally for the removal of introns, which results in the production of more than one mRNA molecule each of that may encode different amino acid sequences. The term splice variant also refers to the proteins encoded by the above cDNA molecules.

"Identity" reflects a relationship between two or more polypeptide sequences or two or more polynucleotide sequences, determined by comparing the sequences. In general, identity refers to an exact nucleotide to nucleotide or amino acid to amino acid correspondence of the two polynucleotide or two polypeptide sequences, respectively, over the length of the sequences being compared.

Identity" For sequences where there is not an exact correspondence, a identity" may be determined. In general, the two sequences to be compared are aligned to give a maximum correlation between the sequences. This may include inserting "gaps" in either one or both sequences, to enhance the degree of alignment. A identity may be determined over the whole length of each of the sequences being compared (so-called global alignment), that is particularly suitable for sequences of the same or very similar length, or over shorter, defined lengths (so-called local alignment), that is more suitable for sequences of unequal length.

"Similarity" is a further, more sophisticated measure of the relationship between two polypeptide sequences, In general, "similarity" means a comparison between the amino acids of two polypeptide chains, on a residue by residue basis, taking into account not only 0 exact correspondences between a between pairs of residues, one from each of the sequences being compared (as for identity) but also, where there is not an exact correspondence, whether, on an evolutionary basis, one residue is a likely substitute for the other. This likelihood has an associated "score" from which the similarity" of the two sequences can IND then be determined.

Methods for comparing the identity and similarity of two or more sequences are (7110 well known in the art. Thus for instance, programs available in the Wisconsin Sequence Analysis Package, version 9.1 (Devereux J et al, Nucleic Acids Res, 12, 387-395, 1984, (71 available from Genetics Computer Group, Madison, Wisconsin, USA), for example the programs BESTFIT and GAP, may be used to determine the identity between two polynucleotides and the identity and the similarity between two polypeptide sequences.

BESTF1T uses the "local homology" algorithm of Smith and Waterman (J Mol Biol, 147,195-197, 198 1, Advances in Applied Mathematics, 2, 482-489, 198 1) and finds the best single region of similarity between two sequences. BESTFIT is more suited to comparing two polynucleotide or two polypeptide sequences that are dissimilar in length, the program assuming that the shorter sequence represents a portion of the longer. In comparison, GAP aligns two sequences, finding a "maximum similarity", according to the algorithm of Neddleman and Wunsch (I Mol Biol, 48, 443-453, 1970). GAP is more suited to comparing sequences that are approximately the same length and an alignment is expected over the entire length. Preferably, the parameters "Gap Weight" and "Length Weight" used in each program are 50 and 3, for polynucleotide sequences and 12 and 4 for polypeptide sequences, respectively. Preferably, identities and similarities are determined when the two sequences being compared are optimally aligned.

Other programs for determining identity and/or similarity between sequences are also known in the art, for instance the BLAST family of programs (Altschul S F et al, J Mol Biol, 215, 403-410, 1990, Altschul S F et al, Nucleic Acids Res., 25:389-3402, 1997, available from the National Center for Biotechnology Information (NCBI), Bethesda, Maryland, USA and accessible through the home page of the NCBI at www.ncbi.nlm.nih.gov) and FASTA (Pearson W R, Methods in Enzymology, 183, 63-99, 1990; Pearson W R and Lipman D J, Proc Nat Acad Sci USA, 85, 2444-2448,1988, available as part of the Wisconsin Sequence Analysis Package).

t Preferably, the BLOSUM62 amino acid substitution matrix (Henikoff S and Henikoff J G, Proc. Nat. Acad Sci. USA, 89, 10915-10919, 1992) is used in polypeptide Ssequence comparisons including where nucleotide sequences are first translated into amino O acid sequences before comparison.

Preferably, the program BESTFIT is used to determine the identity of a query polynucleotide or a polypeptide sequence with respect to a reference polynucleotide or a Spolypeptide sequence, the query and the reference sequence being optimally aligned and the N parameters of the program set at the default value, as hereinbefore described.

"Identity Index" is a measure of sequence relatedness which may be used to 1 10 compare a candidate sequence (polynucleotide or polypeptide) and a reference sequence.

SThus, for instance, a candidate polynucleotide sequence having, for example, an Identity C Index of 0.95 compared to a reference polynucleotide sequence is identical to the reference sequence except that the candidate polynucleotide sequence may include on average up to five differences per each 100 nucleotides of the reference sequence. Such differences are selected from the group consisting of at least one nucleotide deletion, substitution, including transition and transversion, or insertion. These differences may occur at the 5' or 3' terminal positions of the reference polynucleotide sequence or anywhere between these terminal positions, interspersed either individually among the nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence. In other words, to obtain a polynucleotide sequence having an Identity Index of 0.95 compared to a reference polynucleotide sequence, an average of up to 5 in every 100 of the nucleotides of the in the reference sequence may be deleted, substituted or inserted, or any combination thereof, as hereinbefore described. The same applies mutatis mutandis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99.

Similarly, for a polypeptide, a candidate polypeptide sequence having, for example, an Identity Index of 0.95 compared to a reference polypeptide sequence is identical to the reference sequence except that the polypeptide sequence may include an average of up to five differences per each 100 amino acids of the reference sequence. Such differences are selected from the group consisting of at least one amino acid deletion, substitution, including conservative and non-conservative substitution, or insertion. These differences may occur at the amino- or carboxy-terminal positions of the reference polypeptide sequence or anywhere between these terminal positions, interspersed either individually among the amino acids in the reference sequence or in one or more contiguous groups within the reference sequence. In other words, to obtain a polypeptide sequence having an Identity Index of 0.95 compared to a reference polypeptide sequence, an average of up to P:\OPER\MKRlSPECHdiv 2001292619.doc-25/10/05 0 -23- 0 in every 100 of the amino acids in the reference sequence may be deleted, substituted or D inserted, or any combination thereof, as hereinbefore described. The same applies mutatis mutandis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99.

t The relationship between the number of nucleotide or amino acid differences and M 5 the Identity Index may be expressed in the following equation: na xa (xa I), 0 in which: CI na is the number of nucleotide or amino acid differences, xa is the total number of nucleotides or amino acids in a sequence set forth in the Sequence Listing, I is the Identity Index, is the symbol for the multiplication operator, and in which any non-integer product of xa and I is rounded down to the nearest integer prior to subtracting it from Xa.

"Homolog" is a generic term used in the art to indicate a polynucleotide or polypeptide sequence possessing a high degree of sequence relatedness to a reference sequence. Such relatedness may be quantified by determining the degree of identity and/or similarity between the two sequences as hereinbefore defined. Falling within this generic term are the terms "ortholog", and "paralog". "Ortholog" refers to a polynucleotide or polypeptide that is the functional equivalent of the polynucleotide or polypeptide in another species. "Paralog" refers to a polynucleotide or polypeptide that within the same species which is functionally similar.

"Fusion protein" refers to a protein encoded by two, often unrelated, fused genes or fragments thereof. In one example, EP-A-0 464 533-A discloses fusion proteins comprising various portions of constant region of immunoglobulin molecules together with another human protein or part thereof. In many cases, employing an immunoglobulin Fc region as a part of a fusion protein is advantageous for use in therapy and diagnosis resulting in, for example, improved pharmacokinetic properties [see, EP-A 0232 262].

On the other hand, for some uses it would be desirable to be able to delete the Fc part after the fusion protein has been expressed, detected and purified.

P:\OPER\MKRL PECldiv 2001292619.doc-25/1005 S- 23A O Throughout this specification and the claims which follow, unless the context NO requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group In of integers or steps but not the exclusion of any other integer or step or group of integers or m 5 steps.

CN The reference to any prior art in this specification is not, and should not be taken n as, an acknowledgment or any form of suggestion that that prior art forms part of the Scommon general knowledge in Australia.

All publications and references, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference in their entirety as if each individual publication or reference were specifically and individually indicated to be incorporated by reference herein as being fully set forth. Any patent application to which this application claims priority is also incorporated by reference herein in its entirety in the manner described above for publications and references.

Table 1.

GSK Nucleic Acid ICorresponding Protein Gene Name Gene ED SEQ ED) NO's SEQ U)D NO's sbg960509cbrecpt 960509 SEQ H) NO:1I SEQ ED sbg6l4l26complfHl 614126 SEQ MDNO:2 SEQ ID NO:46 ID NO:3 SEQ ID NO:47 sbgl2O7O3RNase 120703 SEQ ED NO:4 SEQ ID NO:48 sbg98530TS 98530 SEQ ID NO:5 SEQ ID NO:49 SEQ MD NO:6 SEQ DD sbg563917RDP 63917 SEQ ID NO:7 SEQ ID NO:51 ID NO: 8 SEQ DD NO:52 sbg6l8O69LRR 618069 SEQ ID NO:9 SEQ ID NO:53 D NO: 10 SEQ ID NO:54 sbg934114Relaxin 934114 SEQ 1ID NO:1Il SEQ ID sbg99174LOX-like 99174 SEQ ID NO: 12 SEQ DD NO:56 sbg995002PIGR 995002 SEQ ID NO: 13 SEQ ID NO:57 sbglO33026Clq 1033026 SEQ ED NO: 14 SEQ ID NQ:58 ID NO:15 SEQ ID NO:59 sbglO03675RNase 1003675 SEQ lID NO:]16 SEQ lID sbglO15258PLM 1015258 SEQ ID NO: 17 SEQ DNO:61 sbg10033281G 1003328 SEQ ID NO: 18 SEQ ID NO:62 ID NO: 19 SEQ ED NO:63 sbg1020829SGLT 1020829 SEQ ID NO:20 SEQ ID 0O:64 sbgIO0545OUDPGT 1005450 SEQ ID NO:21 SEQ ID SEQ ID NO:22 SEQ MD NO:66 sbglO0262OTIa 1002620 SEQ ED NO:23 SEQ ID NO:67 ED NO:24 SEQ 11) NO:68 sbglO02620TIb 1002620 SEQ ED NO:25 SEQ ID NO:69 sbglO2200MCra 102200 SEQ IID NO:26 SEQ ID ED NO:27 SEQ ID NO:71 sbglO2200MCrb 102200 SEQ ID NO:28 SEQ ID NO:72 sbg102038OLYG 1020380 SEQ ID NO:29 SEQ ID NO:73 ID NO:30 SEQ ID NO:74 sbgl007O26SGLT 1007026 1SEQ ED NO:31 SQI O7 sbg1O12732GLUT 1012732 SEQ lID NO:32 SEQ ID NO:76 ED NO:33 SEQ ID NO:77 sb&1OI2732GLUTb 1012732 SEQ ID NO:34 SEO ID NO:78 sbglO18172CSP 1018172 SEQ H)NO:35 SEQ ID NO:79 SEQ ED NO:36 SEQ H) NO:B0 sbg100457OERGIC 1004570 SEQ ID NO:37 SEQ MD NO:81 SEQ U)NO:38 SEQ DNO:82 sbg1016995IGBrecpt 1016995 SEQ ED NO:39 SEQ ID NO:83 SEQ ED NO:40 SEQ ED NO:.84 1151 SEQ ID NO:1 SEQ ID _SE Q ID N O :42 SEQ ED N O 86 sbg1399854ANK 1399854 SEQ ID NO:43 SEQ ID NO: 87 SE D NO:44 SEQ ID) NO: 88 Table HI Gene Name Gene Closest Polynucleotide Closest Polypeptide by Cell Family by homology homology Localization (by sbg960509 Carbohydra GB :AC007395 Mouse Kupifer cell c- Membranecbrecpt te-binding Direct submitted (25- type lectin receptor, gi: bound receptor APR-1999) Genome 7949066 Submitted Sequencing Center, (25-OCT-1996) to the Washington University DDBJ/EMBLJGenBank School of Medicine, databases.

4444 Forest Park Parkway, St. Louis, MO

USA

sbg614126 Compleme SC:AL353809 Human H-factor like 1, Secreted complfH nt factor H Submitted (20-JAN- gi: 11321587 2001) by Sanger Centre, Estaller,C., Hinxton, Koistinen,V., Cambridgeshire, CB 10 Schwaeble,W., I SA. UK. Dierich,M.P., and Weiss,E.H. 3. Immunol.

146,3190-3196 (1991) sbg120703 RNase GBAL157687 Human kerarinocyte- Secreted RNase Direct Submitted (24- derived RNase-lice MIAY-2000) to the protein, geneseqp: EMBLJGenBank/DDBJ Y44 192 Submitted by databases by Genoscope. INOGENETICS NV Application number and publication date: EP- 943679-Al,. 22-SEP-99 sbg98530T Thrombosp GB :AC027307 Mouse RIKEN cDNA Secreted S ondin type Submitted (30-MAR- 2010109H09 gene, 1 2000) Production gi:13385092 Sequencing Facility, The RIKEN Genome DOE Joint Genome Exploration Research Institute, 2800 Mitchell Group Phase 11 Team Drive, Walnut Creek, and FANTOM CA 94598, USA Consortium. Nature 1 409, 685-690 (2001) sbg563917 Renal GB:AC009077 Human putative Secreted RDP dipeptidase Directly submitted (03- metallopeptidase AUG-1999) by (family M19) Production Sequencing gi: 11641273 Chenj.M., Facility, DOE Joint FortunatoM. and Genome Institute, 2800 Barrett, A.I.

Mitchell Drive, Walnut Submitted (02-NOV- Creek, CA 94598, USA 2000) Chen MRC Molecular Enzymology Laboratory, The Babraham Institute, Babraham, Cambridge, 4AT, UK Tabl icn) Gene Name Gene Closest Polynucleotide by homology Closest Polypeptide by homology Cel Localization (by homology) sbg6 18069

LRR

Leucinerich repeat GB:AL589765 Submitted (16-MAR- 2001) by Sanger Centre, Hinxton, Cambridgeshire, ISA, UK.

Macaca fascicularis brain protein, gi: 9651088 Submitted (28-JL-2000) to the DDBJ/EMVBLIGt.--Bank databases. Katsuyuki Hashimoto, National Institute of Infectious Diseases, Division of Genetic Resources; 23- 1, Toyama 1 -chome, Shinjulcu-ku, Tokyo 162-8640. Jap3an Membranebound sbg9341 14 Insulin JGI:CT978SKB_5506 Mouse insulin-like Secreted Relaxin Found at Joint Genome peptide (relaxin/insulin- Institute like protein), gi:7387805 DoE41LLNIJLIANL. Conklin D, Lofton-Day CE, Haldeman BA, Ching A, Whitmore TE, Lok S, Jaspers S. 1999.

60:50-56. sbg99l74L C-type GB:AL137062 Mouse putative protien, Membrane- OX-like lectin Direct submitted (09- gi: 12855891 The bound AUG-2000) Sanger RIKEN Genome Centre, Hinxton, Exploration Research Cambridgeshire, CB 10 Group Phase H Team I SA, UK. and FANTOM Consortium. Nature 409, 685-690 (2001) sbgc995002 Polymeric GBAC027192 Human TANGO 354 Membrane- PIGR -Direct submitted (28- protein, geneseqp: bound immnublob MAR-2000) Whitehead B 66271 Submitted by ulin Institute/Mi Center for (MILL-) receptor Genome Research, 320 MILLENNIUM (PIGR) Charles Street, PHARM INC Cambridge, MA 02141, Application number and USA. publication date: W0200100673-Al, sbg103302 Clq GB:AL359736 Human adipocyte- Secreted Direct submitted (22- specific secretory 6Clq AUG-2000) Sanger protein, gi: 4757760 Centre, Hinxton, MaedaK., Okubo,K., Cambridgeshire, CB10 ShimomuraI., ISA, UK. Funahashi,T., Matsuzawa,Y. and Matsubara,K.

Biochemn. Biophys. Res.

Cominun. 221 286- 289 (1996) Table 11 (cont).

1* Gne Name

I

Gene Family Closest Polynucleotide by homology Closest Polypeptide by homology Cell Localization (by homoloffv) sbg100367 RNase EML:CNSOIRIH chinchilla brevica udata Secreted Found at European pancreatic ribonuclease, Molecular Biology gi: 133205 Van Den Laboratory. Berg A, Van Den Hende-Timnxer L, Beintema JJ. 1976.

Biochim Biophys Acta sbg101525 Phosphole GB:AL022345 Human Membrane- 8PLM nunan Direct submitted (1O-DEC- phospholemnian-like bound (PLM) 1999) by Sanger Centre, protein, Hinxton, Cambridgeshire, geneseqp:W51 104 CBIO ISA, UK. Submitted by (HUMA-) HUMAN GENOME SCI INC Application number and publication date: W09839448-A2, I1I-SEP-98 sbg100332 Immunogi EMBL:HSBA536C5 Human immune system Membrane- 8IG obulin Found at European molecule, bound Molecular Biology geneseqp:B 15536 Laboratory. Submidtted by (INCY-) INCYTE PHARM INC Application number and publication date: W0200060080-A2, sbg 102082 Na+/gluco GB:AJ009617 Oryctolagus cuniculus Membrane- 9SGLT se Directly submitted (17- Na/glucose bound cotranspor JUL- 1998) by MPIMG, cotransporters, ter Abt.Lehrach, Max Planck gi:520469 Pajor,A.M.

Institut fuer Molekculare 1994 Biochiin.

Genetik, Ihnestrasse 73, Biophys. Acta 1194 Berlin, 14195, Germany. 349-51. UDP- GB:AC016612 Human PR01780 Membrane- OUDPGT glucuronos; Submitted (04-DEC- protein geneseclj: bound yltransfera 1999) Production B24025 se(UDPG Sequencing Facility, DOE Submitted by T) Joint Genome Institute, GENENTECH INC 2800 Mitchell Drive, Application number and Walnut Creek, CA 94598, publication date: USA W0200053750-Al, 14-SEP-00 sbg100262 Cysteine- GB:AC025280 Human hypothetical Secreted 071a rich Submitted (08-MAR- protein secretory 2000) by Production DKFZp434BO44, gi: protein Sequencing Facility, DOE 13899332 Wiemann,S., (CRISP) Joint Genonie Institute, Weil,B. et al. Genome trypsin 2800 Mitchell Drive, Res. 11 422-435 inhibitor Walnut Creek, CA 94598, (2001)

USAIII

Table RI (cont).

Gene Name Gene Closest Polynucleotide Closest Polypeptide by Cell Family by homology homology Localization (by sbg100262 Cysteine- GB:AC025280 Rat late gestation lung Secreted rich Submitted (08-MAR- protein 1 gi:4324682 OTIb secretory 2000) by Production Kaplan,F., Ledoux,P., protein Sequencing Facility, DOE Kassamali,F.Q., (CRISP) Joint Genome Institute, Gagnon,S.. Post,M., trypsin 2800 Mitchell Drive, Koehler,D., Deimlding,J.

inhibitor Walnut Creek, CA 94598, and Sweezey,N.B.

USA Am. J. Physiol. 276 (1999) sbg 102200 Monocarb GB: AC015918 Mouse unnamed Membrane- MCTa oxylate Directly submitted (17- protein product, bound cotranspor NOV-1999) by gi:7670446 Submitted ter Whitehead Institutellvlr (I12-APR-2000) to the (McT1) Center for Genome DDBJ/EM]BIGenBank Research, 320 Charles databases by Katsuyuki Street, Cambridge, MA Hashimoto, National 02141, USA. Institute of Infectious Diseases, Division of Genetic Resources; 23- 1, Toyama, 1-chome, Shinjuku-ku, Tokyo 162-8640, Japan sbg102200 Monocarb GB: AC015918 Human solute carrier 16 Membrane- MCTb oxylate Directly submitted (17- (monocarboxylic acid bound cotranspor NOV- 1999) by transporters), member ter Whitehead Institute/MIT 8, gi:13655082 (MCI' 1) Center for Genome Submitted (17-APR- Research, 320 Charles 2001) by National Street, Cambridge, MA Center for 02141, USA. Biotechnology Information, NIH, Bethesda, MD 20894, sbg 102038 Goose- GB :AC023 965 Lysozyme G (1,4-beta- Secreted type Directly submitted (20- N-acetylmuramidas E) OLYG lysozyme FEB-2000) by Whitehead (Goose-type lysozyme).

G Institute/MIT Center for gi:126634 Schoentgen, Genome Research, 320 Jolles,J. and Jolles, Charles Stree, P. Eur. J. Biochem- 123 Cambridge, M.A 0214 1, 489-497 (1982) sbglOO7O2 Sodium- GB:AC046167 Human transport Membrane- 6SGLT glucose Direct submitted (13- protein TPPT- 13, bound cotranspor APR-2000) Whitehead geneseqp: B60093 ter Institute/MIT Center for Submitted by INCYTE Genome Research, 320 GENOMICS INC Charles Street, Application number and Cambridge, MA 0214 1. publication date: W0200078953-A2, 28-DEC-00 Tble U (cont) Gene Name Gene Closest Polynucleotide Closest Polypeptide by 1Cell Family by homology homology jLocalization I(by jhomology) sbg101273 Guoe G:P03 Human glucose Membranetransporte Direct submitted (10- transporter GLUT 10, bound '2GLUT r JUN-1999) to the gi:13540598 DDBJIEMBIJGenBank Submitted (lO-FEBdatabases. Nobuyoshi 2000) Joost H.G., Shimizu, Keio university, Institute of school of medicine, Pharmacology and Molecular Biology; 35 Toxicology, Medical Shinanomachi, Shinjuku- Faculty, Technical 1w, Tokyo 160-0016, University of Aachen, Japan. Wendlingweg 2, Aachen, D-52057,

GERMANY_____

sbg101273 Guoe G:P03 Human glucose Membranetransporte Direct submitted (10- transporter GLUTIO, bound 2GLUTb r JUN.1999) to the gi:13540598 DDBJIEMBLJGenBank Submitted (lO-FEBdatabases. Nobuyoshi 2000) Joost H.G., Shimizu, Keio university, Institute of school of medicine, Pharmacology and Molecular Biology; 35 Toxicology, Medical Shinanomachi, Shinjuku- Faculty, Technical 1w, Tokyo 160-0016, University of Aachen, Japan. Wendlingweg 2, Aachen, D-52057,

GERMANY

sbglOl 817 Chondroit EMBL:AL3548 19, Lytechinus variegatus Secreted in sulfate and SC:AL-590007. embryonic blastocoelar 2CSP proteoglyc Submitted (30-APR-2001 extracellular matrix an and 04-MAY-2001) by protein gi:9837426 Sanger Centre, Hinxton, Submitted (14-JUL- Cambridgeshire, CBIO 2000) Biological I SA, UK. Sciences, Carnegie EMBL:AC0171 111, Mellon University, Submitted (09-DEC- 4400 Fifth Aye, 1999) Genome Pittsburgh, PA 15213, Sequencing Center, USA Washington University School of Medicine, 4444 Forest Park Parkway, St.

Louis, MO 63108, USA sbg100457 ER-Golgi GB:AC020705 Human ERGL protein, Membrane- OEGC intermedia Submitted (08-JAN-2000) gi: 11141891 bound CEGC te Genome Sequencing Submitted (06-SEPcompartln Center, Washington 2000) Laboratory of ent protein University School of Molecular Biology, Medicine, 4444 Forest NCI, NUL 37 Convent Park Parkway, St. Louis, Dr., Bldg. 37, Rm.

MO 63108, USA 41120, Bethesda, MD 20892, Table HI Gene Name Gene Closest Polynucleotide Closest Polypeptide by Cell Family by homology homology Localization (by sbg101699 Immnunogi GB:AL353721 Human Membraneobulin Submitted (07-JUL-2001) immunoglobulin bound 51GBrecpt receptor Sanger Centre, Hinxton, superfamily receptor Cambridgeshire, GB 10 translocation associated I SA, UK. 1, gi:l4550 4 16 Hatzivassiliou,G., MillerI.J., Takizawa, et al. Immunity 14 (2001) sbgllISlbS EGF-like GB:AC005500 Human nurse cell Membrane- LDL Chen,F., Do,T., receptor B6TNC# l0b, bound REC receltor Dumanski,J.P. and geneseqp: B60395 protein Roe,B.A. Direct Submitted by (SFHO) submission (31-MAY-01) SHIONOGI CO LTD Department Of Chemistry Application number and and Biochemistry, The publication date: *University Of Oklahoma, JP2000308492-A, 620 Parrington Oval, 07-NOV-00 Room 208, Norman, OK 73019, USA sbS139985 The GB: AC020658 Human KIAA1223 Cytosolic ankyrin Direct submitted (08- protein, gi:6330617 4ANK repeat JAN-2000) Nagase T, Ishikawa K family Multimegabase Kikuno R- Hirosawa M, Sequencing Center, Nomura N, and Ohara University of 0; 1999 DNA Res Washington, PO BOX 6:337-45.

357730, Seattle, WA

USA

Table mII Gene Name Uses Associated Diseases sbg960509 An embodiment of the invention is the use of Autoimmune sbg960509cbrecpt in the treatment or diagnosis of cancer. disorder and cbrecpt A close homologue of sbg960509cbrecpt is Langerin. cancer Langerin was a type II Ca2+-dependent lectin, an endocytic receptor and expressed by Langerhans cells (LC).

Transfection of Langerin cDNA into fibroblasts created a compact network of membrane structures with typical features of Birbeck granules(BG). It was proposed that induction of BG was a consequence of the antigen-capture function of Langerin, allowing routing into these organelles and providing access to a nonclassical antigen-processing pathway (Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S. 2000.

Immunity Jan;12(1):71-81). A striking incongruity was found between variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver cells (Paietta E, Stockert RJ, Racevskis J. 1992. Hepatology Mar;15(3):395-402). Human macrophage cell surface C-type lectin was demonstrated to recognize Tn Ag, a well-known human carcinoma-associated epitope (Suzuki N, Yamamoto K, Toyoshima S, Osawa T, Irimura T.1996. J Immunol Jan 1;156(1):128-35).

sbg614126 An embodiment of the invention is the use of Alzheimer's sbg614126complfH in the diagnosis or treatment of cancer, disease, cancer, complfH Alzheimer disease, and/or tumor cell evasion, tumor metastasis A close homologue of sbg614126complfH is Human and autosomal complement factor H. Human complement factor H was recessive atypical detected by the AM34 antibody in the cerebrospinal fluid hemolytic uremic from an Alzheimer's disease patient. It was recently found syndrome that AM34 was capable of staining senile plaques positively and factor H was associated with senile plaques in the human brain (Honda S, Itoh F, Yoshimoto M, Ohno S, Hinoda Y, Imai K. 2000. J Gerontol A Biol Sci Med Sci.

May;55(5):M265-9). It was also suggested that exceptional resistance of human H2 glioblastoma cells to complementmediated killing was due to the production and binding of factor H and factor H-like protein 1 (Junnikkala S, Jokiranta TS, Friese MA, Jarva H, Zipfel PF, Meri S. 2000. J Immunol.

Jun 1;164(11):6075-81). Moreover, factor H was shown to bind to bone sialoprotein and osteopontin and enable tumor cell evasion of complement-mediated attack (Fedarko NS, Fohr B, Robey PG, Young MF, Fisher LW. 2000. J Biol Chem. Jun 2;275(22): 16666-72). .Finally, complement factor H gene mutation was associated with autosomal recessive atypical hemolytic uremic syndrome (Ying L, Katz Y, Schlesinger M, Carmi R, Shalev H, Haider N, Beck G, Sheffield VC, Landau D. 1999. Am J Hum Genet Dec;65(6):1538-46).

Table m (cont).

Gene Name IUses Associated e Diseases sbg120703 An embodiment of the invention is the use of Cancer and sbgl20703Rnase as a tool for anticancer therapy, and treating infection RNase apoptosis-related disorders. It has been shown that a geneticengineered pancreatic RNase has cytotoxic action on mouse and human tumor cells, but lacks any appreciable toxicity on human and mouse normal cells. This variant of human pancreatic RNase selectively sensitized cells derived from a human thyroid tumor to apoptotic death. Because of its selectivity for tumor cells, and because of its human origin, this protein is thought to represent a promising tool for anticancer therapy (Piccoli R, Di Gaetano S, De Lorenzo C, Grauso M, Monaco C, Spalletti-Cernia D, Laccetti P, Cinatl J, Matousek J, D'Alessio G. 1999. Proc Natl Acad Sci U S A 96:7768-73). In addition, RNase itself can be used to treat an RNA viral infection, and its antagonist may be useful in treating apoptosis-related disorders.

sbg98530T An embodiment of the invention is the use of sbg98530TS in Cancer, wound the wound healing processes, development of the nervous healing disorders S system, and affecting cell migration, survival, or angiogenesis. Close homologues of sbg98530TS are thrombospondins. The thrombospondins are a family of proteins found widely in the embryonic extracellular matrix, and the expression patterns and in vitro properties of many thrombospondins suggest potential roles in the guidance of cell and growth cone migration, especially during the development of the nervous system (Adams JC, 2000. Tucker RP Dev Dyn 218:280-99). Cell interactions with extracellular matrices are important to pathological changes that occur during cell transformation and tumorigenesis. The thrombospondin-1 has been suggested to modulate tumor phenotype by affecting cell migration, survival, or angiogenesis (Liaw L, Crawford HC. 1999. Braz J Med Biol Res 32:805-12). In addition, thrombospondin-1 is also a transient component of extracellular matrix in developing and repairing tissues (Adams JC. 1997. Int J Biochem Cell Biol 29:861-5).

sbg563917 An embodiment of the invention is the use of sbg563917RDP Renal diseases, in treatment or diagnosis of chronic renal failure and aged eye aging, cataract, RDP lenses and cataracts. Close homologues of sbg563917RDP cancer, and are renal and lens dipeptidases. It has been reported that the Alzheimer renal dipeptidase activity was significantly lower in the disease chronic renal failure group (Fukumura Y, Kera Y, Oshitani S, Ushijima Y, Kobayashi I, LiuZ, Watanabe T, Yamada R, Kikuchi H, Kawazu S and Yabuuchi M. 1999 Ann Clin Biochem Mar;36 Pt 2):221-5). In contrast, increased lens dipeptidase activity was detected in aging and cataracts (Sulochana KN, Ramakrishnan S and Punitham R.1999 Br J Ophthalmol Jul;83(7):885).

Table m (cont) Gene Name Uses Associated Diseases sbg618069 An embodiment of the invention is the use of sbg618069LRR Tango-associated in treatment or diagnosis of neural development and the adult diseases, LRR nervous system disorders. Close homologues of disorders sbg618069LRR are Leucine-rich repeat proteins. Leucine-rich associated with repeat protein, the spineless-aristapedia, has been shown to the preservation interact with tango bHLH-PAS proteins for controlling and maintenance antennal and tarsal development in Drosophila (Emmons RB, of gastrointestinal Duncan D, Estes PA, Kiefel P, Mosher JT, Sonnenfeld M, mucosa and the Ward MP, Duncan I and Crews ST. 1999. Development repair of acute Sep;126(17):3937-45). In mouse, neuronal Leucine-Rich and chronic Repeat NLRR-1 and NLRR-2 mRNAs were expressed mucosal lesions, primarily in the central nervous system and may play Parkinson's significant but distinct roles in neural development and in the disease, adult nervous system (Taguchi A, Wanaka A, Mori T, Alzheimer's Matsumoto K, Imai Y, Tagaki T and Tohyama M. 1996. disease, ALS, Brain Res Mol Brain Res Jan;35(1-2):31-40). Furthermore, a neuropathies, new member of the leucine-rich repeat superfamily GAC1 cancer, wound was amplified and overexpressed in malignant gliomas healing and tissue (Almeida A, Zhu XX, Vogt N, Tyagi R, Muleris M, repair Dutrillaux AM, Dutrillaux B, Ross D, Malfoy B and Hanash S. 1998. Oncogene Jun 11;16(23):2997-3002).

sbg934114 An embodiment of the invention is the use of Cancer, sbg934114Relaxin in treatment or diagnosis of collagen rheumatic Relaxin remodeling, breast cancer, and uterine contractile disorders. A diseases, heart close homologue of sbg934114Relaxin is Relaxin. Relaxin diseases, has various biologic activities, including the induction of systemic collagen remodeling and consequent softening of the tissues sclerosis of the birth canal during delivery, the inhibition of uterine (scleroderma), contractile activity, and the stimulation of growth and and preterm birth differentiation of the mammary gland (Bani D. 1997. Gen Pharmacol 28:13-22). Relaxin belongs to the insulin superfamily, and is produced primarily by the corpus luteum in both pregnant and nonpregnant females. In males, relaxin is synthesized in the prostate and released in the seminal fluid (Goldsmith LT, Weiss G, Steinetz BG. 1995. Endocrinol Metab Clin North Am 24:171-86). It has been further demonstrated that relaxin regulates growth and differentiation of breast cancer cells in culture, promotes dilation of blood vessels in several organs, including the uterus, the mammary gland, the lung and the heart, has a chronotropic action on the heart, inhibits the release of histamine by mast cells, depresses aggregation of platelets and their release by megakaryocytes, and influences the secretion of hormones by the pituitary gland (Bani D. 1997. Gen Pharmacol 28:13-22).

In addition, some reports have shown that relaxin is effective in decreasing skin involvement in systemic sclerosis (Furst DE. 1998. Curr Opin Rheumatol 10:123-8).

Table m (cont).

Gene Name Uses Associated Diseases sbg99174L An embodiment of the invention is the use of Cardiovascular sbg99174LOX-like in treatment or diagnosis of endothelial disorders (e.g.

OX-like function or atherosclerosis. A close homologue of atherosclerosis, sbg99174LOX-like is oxidized low-density lipoprotein hypertension, receptor 1. sbg99174LOX-like as well as oxidized low- stroke), density lipoprotein receptor 1, contain a C-type lectin domain (CTL) (Colonna M, Samaridis J, Angman L. 2000. Eur J Immunol 30:697-704). Evidence suggests that oxidized lowdensity lipoprotein (OxLDL) plays a critical role in the changes in endothelial function. Lectin-like OxLDL receptor- 1 (LOX-1) is the major endothelial OxLDL receptor.

Functional changes of endothelial cells are implicated in the earliest stage of the pathogenesis of atherosclerosis (Aoyama T, Sawamura T, Furutani Y, Matsuoka R, Yoshida MC, Fujiwara H, Masaki T. Biochem J. 1999 339 (Pt 1):177-84).

sbg95002 An embodiment of the invention is the use of Infection and 2 sbg995002PIGR to actively transport IgA and IgM to the inflammation PIGR apical surface of epithelia. A close homologue of such as sbg995002PIGR is polymeric-immunoglobulin receptor. The inflammatory polymeric-immunoglobulin receptor binds polymeric IgA and bowel disease, IgM at the basolateral surface of epithelial cells. PIGR gluten-sensitive knockout mice completely lack active external IgA and IgM enterropathy, and translocation, but remain normal and fertile (Johansen FE, urinary tract Pekna M, Norderhaug IN, Haneberg B, Hietala MA, Krajci P, infection) Betsholtz C, Brandtzaeg P. 1999. J Exp Med 190:915-22). In addition, it has been reported that PIGR can be upregulated by tumor necrosis factor (TNF)-alpha (Takenouchi-Ohkubo N, Takahashi T, Tsuchiya M, Mestecky J, Moldoveanu Z, Moro I; 2000. Immunogenetics 51:289-95).

sbg103302 An embodiment of the invention is the use of sbg1033026Clq Central nervous 6Clq to regulate central nervous system functions. A close system disorder homologue of sbg1033026C1q is Clq-related factor.

Clq is a subunit of the C1 enzyme complex that activates the serum complement system. It has been shown that human Clq-related factor (CRF) transcript is expressed at highest levels in the brain, particularly in the brainstem. Similarly, in mouse brain CRF transcripts are most abundant in areas of the nervous system involved in motor function (Berube NG, Swanson XH, Bertram MJ, Kittle JD, Didenko V, Baskin DS, Smith JR, and Pereira-Smith OM., 1999, Brain Res. Mol.

Brain Res. 63:233-240). Moreover, ACRP30 is structurally similar to complement factor Clq, and it forms large homooligomers that undergo a series of post-translational modifications. ACRP30 proteins may be a factor that participates in the complex balanced system of energy homeostasis involving food intake, carbohydrate catabolism, and lipid catabolism (Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF; 1995; J Biol Chem 270:26746-9).

sbg100367 An embodiment of the invention is the use of Viral infection, sbg1003675RNase as a promising tool for anticancer therapy, and tumor and apoptosis-related disorders. A close homologue of sbgl003675RNase is RNase. It has been shown that a genetic-engineered pancreatic RNase has cytotoxic action on mouse and human tumor cells, but lacks any appreciable toxicity on human and mouse normal cells. This variant of human pancreatic RNase selectively sensitized cells derived from a human thyroid tumor to apoptotic death. Because of its selectivity for tumor cells, and because of its human origin, this protein was thought to represent a promising tool for anticancer therapy (Piccoli R, Di Gaetano S, De Lorenzo C, Grauso M, Monaco C, Spalletti-Cernia D, Laccetti P, Cinatl J, Matousek J, D'Alessio G. 1999. Proc Natl Acad Sci U S A 96:7768-73). Moreover, RNase itself can be used to treat an RNA viral infection, and its antagonist of this RNase may be useful in treating apoptosis-related disorders.

sbg101525 An embodiment of the invention is the use of Myotonic 8PLM sbgl015258PLM to regulate skeletal and cardiac muscle muscular disorders. A close homologue of sbgl015258PLM is dystrophy phospholemman. The phospholemman (PLM) is enriched in skeletal muscle and the heart, and is a major substrate phosphorylated in response to insulin and adrenergic stimulation. All phospholemman proteins are small and have a single transmembrane domain (Chen LS, Lo CF, Numann R, Cuddy M. 1997. Genomics 41:435-4). Phospholemman can be phosphorylated by protein kinases A and C to induce a hyperpolarization-activated chloride current, and therefore may play a role in muscle contraction. Recently phospholemman was shown to be a substrate for myotonic dystrophy protein kinase, and therefore is associated with the disease, an autosomal dominant-inherited disorder with prominent effects on skeletal and cardiac muscle (Mounsey JP, John JE 3rd, Helmke SM, Bush EW, Gilbert J, Roses AD, Perryman MB, Jones LR, Moorman JR. 2000. J Biol Chem ;275:23362-7).

sbg100332 An embodiment of the invention is the use of Cancer, infection, 8IG sbg1003328IG to generate immunosuppressants to suppress autoimmune immune responses. A close homologue of sbgl003328IG is disorder, V7, a human leukocyte surface protein (Stockinger H, Gadd hematopoietic SJ, Eher R, Majdic O, Schreiber W, Kasinrerk W, Strass B, disorder, wound Schnabl E, Knapp W. 1990. J Immunol 145:3889-97). healing disorders, sbgl003328IG is an immunoglobulin (Ig)-like membrane and inflammation protein containing three potential Ig domains, and it has an overall strong sequence similarity to V7.

sbgl02082 An embodiment of the invention is the use of Cancer, infection, 9SGLT sbgl020829SGLT to regulate Na(+)-dependent glucose autoimmune transport. A close homologue of sbg1020829SGLT is disorder, Na+/glucose cotransporters. The human intestinal Na+/glucose hematopoietic cotransporter (SGLTI) was cloned and sequenced. Close disorder, wound homology was observed between the human and rabbit healing disorders, intestinal Na+/glucose cotransporters, and a significant inflammation and homology was found between these and the Escherichia coli glucose/galactose Na+/proline cotransporter (putP) indicating that the mammalian malabsorption Na+/glucose and prokaryote Na+/proline cotransporters sharing a common ancestral gene (Hediger MA, Turk E, Wright EM.

1989 Proc Natl Acad Sci U S A Aug;86(15):5748-52). In addition, study of intestinal biopsies of glucose/galactose malabsorption (GCM)patients has revealed a specific defect in Na(+-4dependent absorption of glucose in the brush border. A single missense mutation was found in SGLT1 amplified from the genomic DNA derived from members of a family affected _with GGM. This mutated SGLTI cosegregated with the GGM phenotype and resulted in a complete loss of Na(+)-dependent glucose transport in Xenopus oocytes injected with this complementary RNA (Turk E, Zabel B, Mundlos S, Dyer J, Wright EM. 1991 Nature Mar 28;350(6316):354-6).

sbg100545 An embodiment of the invention is the use of Cancer, infection, OUDPGT sbg1005450UDPGT to regulate estrogen and androgen autoimmune catabolism in peripheral steroid target tissues. A close disorder, homologue of sbgl005450UDPGT is UDP- hematopoietic glucuronosyltransferase (UDPGT) gene. Mutations had been disorder, wound found in the promoter and coding regions of UDP- healing disorders, glucuronosyltransferase (UDPGT) gene in seven patients with inflammation Crigler-Najjar syndrome type I caused by reduction in hepatic Gilbert bilirubin UDPGT activity (Yamamoto K, Soeda Y, Kamisako T, syndrome, Hosaka H, Fukano M, Sato H, Fujiyama Y, Adachi Y, Satoh Y, Crigler-Najjar Bamba T. 1998. J Hum Genet 43(2):111-4). A case of Gilbert syndrome (CN) syndrome caused by a homozygous missense mutation of the type II, and bilirubin UDPGT gene was also reported (Maruo Y, Sato H, steroid hormone Yamano T, Doida Y, Shimada M. 1998. J Pediatr catabolism Jun;132(6):1045-7). In addition, monkey UDPGT UGTIA9 malfunction had been cloned and the mRNA was expressed in extrahepatic estrogen-responsive tissues indicating its potential role in estrogen metabolism (Albert C, Vallee M, Beaudry G, Belanger A, Hum DW. 1999. Endocrinology Jul;140(7):3292- 3 0 2).

Human UDPGT UGT2B23 transcript was also expressed in extrahepatic tissues including prostate, mammary gland, epididymis, testis, and ovary. The activity of UGT2B23 was tested with 62 potential endogenous substrates and was demonstrated to be active on 6 steroids and the bile acid, hyodeoxycholic acid suggesting that UGT2B23 might play an important role in estrogen and androgen catabolism in peripheral steroid target tissues (Barbier O, Levesque E, Belanger A, Hum DW. 1999. Endocrinology Dec;140(12):5538-48).

sbg100262 An embodiment of the invention is the use of sbgl002620TIa Cancer, infection, OTIa to regulate human tumor cells. A close homologue of autoimmune sbgl002620TIa is human hypothetical protein disorder, DKFZp434B044. This gene is also similar to trypsin inhibitor hematopoietic which contains Sc7 family of extracellular domains at its N- disorder, wound ternimal region (Genome Res. 11 422-435 (2001)). healing disorders, Trypsin inhibitor P25TI sequence had similarity to CRISP inflammation, family proteins including insect venom allergens, mammalian blood coagulation testis-specific proteins and plant pathogenesis-related proteins. disorders, cellular mRNA encoding P25TI and another two glioma pathogenesis- adhesion related protein GliPR and RTVP-1, which were also shown to disorders, be structurally similar to CRISP family proteins was frequently pancreatitis, expressed in human tumor tissues but not detected in normal shock, multihuman tissue cell lines (Yamakawa T, Miyata S, Ogawa N, organ failure, and Koshikawa N, Yasumitsu H, Kanamori T, Miyazaki K 1998. gastrointestinal Biochim Biophys Acta Jan 21; 1395(2):202-8., Murphy EV, ulceration Zhang Y, Zhu W, Biggs J. 1995. Gene Jun 14;159(1):131-5., Rich T, Chen P, Furman F, Huynh N, Israel MA.1996. Gene Nov 21;180(1-2):125-30).

00262 An embodiment of the invention is the use of Cancer, infection, sbg sbg 002620TIb as a marker for some nervous system tumors, autoimmune OTIb and to regulate expression of human neuroblastoma and disorder, glioblastoma. A close homologue of sbg1002620TIb is late- hematopoietic gestation lung 1 (LGL1) protein. Late-gestation lung 1 disorder, wound (LGL1) protein showed 81% homology to P25TI, the trypsin healing disorders, inhibitor purified from the culture medium of human glioblastoma cells (Kaplan F, Ledoux P, Kassamali FQ, Gagnon S, Post M, Koehler D, Deimling J, Sweezey NB.

1999. Am J Physiol Jun;276(6 Pt 1):L1027-36; Koshikawa N, Nakamura T, Tsuchiya N, Isaji M, Yasumitsu H, Umeda M, Miyazaki K. 1996. J Biochem (Tokyo) Feb;119(2):334- The cDNA encoding P25TI was isolated and the sequence had similarity to CRISP family proteins including insect venom allergens, mammalian testis-specific proteins and plant pathogenesis-related proteins. P25TI mRNA was frequently expressed in human neuroblastoma and glioblastoma but not detected in normal human tissues cell lines (Yamakawa T, Miyata S, Ogawa N, Koshikawa N, Yasumitsu H, Kanamori T, Miyazaki K 1998. Biochim Biophys Acta Jan 21; 1395(2):202- Another two glioma pathogenesis-related protein GliPR and RTVP-1 were also shown to be structurally similar to CRISP family proteins. The GLIPR gene was highly expressed in the human brain tumor, glioblastoma multiforme/astrocytoma, but neither in normal fetal or adult brain tissue, nor in other nervous system tumors (Murphy EV, Zhang Y, Zhu W, Biggs J. 1995.

Gene Jun 14;159(1):131-5). Multiple RTVP-1 mRNA species were highly expressed in a panel of cell lines from nervous system tumors arising from glia, in contrast, the expression of these RNAs was low or absent in nonglial-derived nervous system tumor cell lines (Rich T, Chen P, Furman F, Huynh N, Israel MA.1996. Gene Nov 21;180(1-2):125-30).

inflammation, blood coagulation disorders, cellular adhesion disorders, pancreatitis, shock, multiorgan failure, and gastrointestinal ulceration sbg102200 MCTa An embodiment of the invention is the use of sbg102200MCTa in regulating cancer cells, including the hematopoietic lineages, Burkitt's lymphoma, and solid tumor cells. A close homologue of sbg102200MCTa is MCT1 from Chinese hamster and mouse. Mouse H+-monocarboxylate cotransporter (MCTI) was cloned and sequenced from Ehrlich Lettre tumour cells, the sequence of MCT1 is 93% and 87% homologous to MCT1 from Chinese hamster and human, respectively. N-glycanase-F treatment and an in vitro translation experiments demonstrated that glycosylation was not required for MCT1 function (Carpenter L, Poole RC, Halestrap AP. 1996. Biochim Biophys Acta Mar 13;1279(2):157-63). Chick monocarboxylate transporter MCT3 cloned from retinal pigment epithelium (RPE) cDNA library was found only expressed in RPE cells. A rat thyroid epithelial cell line FRTL transfected with pCl-neo/MCT3 showed enhanced pyruvate uptake suggesting that MCT3 may regulate lactate levels in the interphotoreceptor space (Yoon H, Fanelli A, Grollman EF, Philp NJ. 1997. Biochem Biophys Res Commun May 8;234(1):90-4). In human, MCT2 had been implicated as a primary pyruvate transporter in man.

The mRNAs of MCTI and MCT2 were found co-expressed in various human cancer cell lines, including the hematopoietic lineages HL60, K562, MOLT-4, Burkitt's lymphoma Raji, and solid tumor cells such as SW480, A549, and G361.

These findings suggested that human MCTI and MCT2 may have distinct biological roles (Lin RY, Vera JC, Chaganti RS, Golde DW. 1998. J Biol Chem Oct 30:273(44):28959-65).

Cancer, infection, autoimmune disorder, hematopoietic disorder, wound healing disorders, and inflammation sbg102200 An embodiment of the invention is the use of Cancer, infection, MCTb sbgl02200MCTb in regulating cancer cells, including the autoimmune hematopoietic lineages, Burkitt's lymphoma, and solid tumor disorder, cells. A close homologue of sbg102200MCTb is MCT1 from hematopoietic SChinese hamster and mouse. Mouse H+-monocarboxylate disorder, wound Ci cotransporter (MCTI) was cloned and sequenced from healing disorders, SEhrlich Lettre tumour cells, the sequence of MCT1 is 93% and inflammation o and 87% homologous to MCT1 from Chinese hamster and 0 human, respectively. N-glycanase-F treatment and an in vitro translation experiments demonstrated that glycosylation was Ci not required for MCT1 function (Carpenter L, Poole RC, Halestrap AP. 1996. Biochim Biophys Acta Mar 13;1279(2):157-63). Chick monocarboxylate transporter V MCT3 cloned from retinal pigment epithelium (RPE) cDNA DO library was found only expressed in RPE cells. A rat thyroid Cc epithelial cell line FRTL transfected with pCl-neo/MCT3 showed enhanced pyruvate uptake suggesting that MCT3 may Ci regulate lactate levels in the interphotoreceptor space (Yoon V H, Fanelli A, Grollman EF, Philp NJ. 1997. Biochem Biophys Res Commun May 8;234(1):90-4). In human, MCT2 had 0been implicated as a primary pyruvate transporter in man.

C The mRNAs of MCT1 and MCT2 were found co-expressed in various human cancer cell lines, including the hematopoietic lineages HL60, K562, MOLT-4, Burkitt's lymphoma Raji, and solid tumor cells such as SW480, A549, and G361.

These findings suggested that human MCT1 and MCT2 may have distinct biological roles (Lin RY, Vera JC, Chaganti RS, Golde DW. 1998. J Biol Chem Oct 30;273(44):28959-65).

sbg102038 An embodiment of the invention is the use of Cancer, infection, OLYG sbg1020380LYG in the immune system and enhance the autoimmune activity of immunoagents and may serve as biomarkers of disorder, periodontal disease activity. Close homologues of hematopoietic sbgl020380LYG are lysozymes. Lysozymes are bacteriolytic disorder, wound defensive agents and have been adapted to serve a digestive healing disorders, function (Qasba PK, Kumar S, 1997, Crit Rev Biochem Mol and inflammation Biol 32:255-306). Those in tissue and body fluids are involved in the immune system and enhance the activity of immunoagents. Llysozymes may serve as biomarkers of periodontal disease activity from inflammatory cell origin (Eley BM, and Cox SW, 1998, Br Dent J 184:323-8).

sbgl00702 An embodiment of the invention is the use of Glucose/galactos 6SGLT sbgl007026SGLT, a human sodium-glucose cotransporter, in e malabsorption regulation of Glucose/galactose malabsorption (GGM), familial (GGM), familial renal glycosuria, and diabetic renal disorders. Close renal glycosuria, homologues of sbgl007026SGLT are other sodium-glucose and diabetic renal cotransporters from humans and rabbits. Human sodium- disorders glucose cotransporters are responsible for the active accumulation of glucose in cells (Hediger MA, Turk E, Wright EM. 1989. Proc Natl Acad Sci U S A 86:5748-52).

The renal sodium-glucose cotrnasporter may be related to the pathophysiology of renal diseases such as familial renal glycosuria and diabetic renal disorders (Kanai Y, Lee WS, You G, Brown D, Hediger MA. 1994. J Cin Invest 93:397- 404). In addition, study of glucose/galactose malabsorption (GGM) patients has revealed a specific defect in sodiumdependent absorption of glucose in the brush border, and the consequent severe diarrhea and dehydration caused by glucose/galactose malabsorption are usually lethal unless these sugars are eliminated from the diet (Turk E, Zabel B, Mundlos S, Dyer J, Wright EM. 1991 Nature 350:354-6).

I

sbg101273 2GLUT An embodiment of the invention is the use of sbg1012732GLUT, in the maintenance of cellular homeostasis and metabolism. Close homologues of sbgl012732GLUT are transmembrane glucose transporters (gluts). Glucose uptake is achieved by transmembrane glucose transporters.(gluts), and the transport of glucose across plasma membranes is important for the maintenance of cellular homeostasis and metabolism. Glucose is taken up by cells and then phosphorylated to glucose-6-phosphate, and lucose utilization by cancer cells is greatly enhanced when compared with that by normal tissue. Tumor tissue is frequently associated with the abnormal and/or overexpression of glucose transporters, especially glutl (Smith TA. 1999. Br J Biomed Sci 56:285-92). Increased utilization of glucose in glomerular cells cause the increased expression and activity of aldose reductase, protein kinase C and TGFbeta, which have been implicated in excessive extracellular matrix accumulation in diabetic nephropathy (Z Katedry i Zakladu Patofizjologii, Akaemii Medycznej w Poznaniu.

1999. Przegl Lek 56:793-9). Changes in endothelial glucose transport and GLUT1 abundance in the barriers of the brain and retina may severely affect glucose delivery to these tissues and major implications in the development of two major diabetic complications, insulin-induced hypoglycemia and diabetic retinopathy (Kumagai AK. 1999. Diabetes Metab Res Rev 15:261-73).

Tumor, diabetic nephropathy, and insulin-induced hypoglycemia sbg101273 2GLUTb An embodiment of the invention is the use of sbgl012732GLUTb, in the maintenance of cellular homeostasis and metabolism. Close homologues of sbg 1012732GLUTb are transmembrane glucose transporters (gluts). Glucose uptake is achieved by transmembrane glucose transporters (gluts), and the transport of glucose across plasma membranes is important for the maintenance of cellular homeostasis and metabolism. Glucose is taken up by cells and then phosphorylated to glucose-6-phosphate, and lucose utilization by cancer cells is greatly enhanced when compared with that by normal tissue. Tumor tissue is frequently associated with the abnormal and/or overexpression of glucose transporters, especially glutl (Smith TA. 1999. Br J Biomed Sci 56:285-92). Increased utilization of glucose in glomerular cells cause the increased expression and activity of aldose reductase, protein kinase C and TGFbeta, which have been implicated in excessive extracellular matrix accumulation in diabetic nephropathy (Z Katedry i Zakladu Patofizjologii, Akaemii Medycznej w Poznaniu.

1999. Przegl Lek 56:793-9). Changes in endothelial glucose transport and GLUT1 abundance in the barriers of the brain and retina may severely affect glucose delivery to these tissues and major implications in the development of two major diabetic complications, insulin-induced hypoglycemia and diabetic retinopathy (Kumagai AK. 1999. Diabetes Metab Res Rev 15:261-73).

I

Tumor, diabetic nephropathy, and insulin-induced hypoglycemia sbgl01S7 An embodiment of the invention is the use of Melanoma, sbgl018172CSP in regulation of melanoma, autoimmune infection, 2CSP disorders, hematopoietic disorder, wound healing, and autoimmune inflammation. A close homologue of sbgl018172CSP is disorder, melanoma-associated chondroitin sulfate proteoglycan hematopoietic 1 (MCSP) core protein NG2. The MCSP core protein NG2 can act as a coreceptor for spreading and focal contact formation in association with alpha 4 beta 1 integrin in melanoma cells (lida J, Meijne AM, Spiro RC, Roos E, Furcht LT, McCarthy JB. 1995. Cancer Res Mar 15;55(10):2177-85). Cloning of MCSP recognized by mAb 9.2.27 showed that the core protein contained an open reading frame of 2322 AAs, encompassing a large extracellular domain, a hydrophobic transmembrane region, and a relatively short cytoplasmic tail.

MCSP RNA was detected in human melanoma cell lines and in biopsies prepared from melanoma skin metastases but not in other human cancer cells or a variety of human fetal and adult tissues (Pluschke G, Vanek M, Evans A, Dittmar T, Schmid P, Itin P, Filardo EJ, Reisfeld RA. 1996. Proc Natl Acad Sci U S A Sep 3;93(18):9710-5).

disorder, wound healing, and inflammation sbgl00457

OERGIC

An embodiment of the invention is the use of sbg1004570ERGIC as a probe for studying protein trafficking in the secretory pathway which is crucial for the elucidation and treatment of many inherited and acquired diseases, such as cystic fibrosis, Alzheimer's disease and viral infectionsin regulation of melanoma, autoimmune disorders, hematopoietic disorder, wound healing, and inflammation. A close homologue of sbgl004570ERGIC is ERGIC-53, an ER-Golgi intermediate compartment (ERGIC) protein. A ERGIC protein was elevated more than two fold in HT-29 colon adenocarcinoma cells resistant to the the antitumor drug KRN5500. Together with other information, the cellular secretory pathway was suggested a primary determinant of sensitivity to KRN550 (Kamishohara M, Kenney S, Domergue R, Vistica DT, Sausville EA. 2000 Exp Cell Res May 1;256(2):468-79). Mutations in ERGIC-53 was shown to cause combined deficiency of coagulation factors V and VIII and it was suggested that ERGIC-53 might function as a molecular chaperone for the transport from ER to Golgi of a specific subset of secreted proteins, including coagulation factors V and VII (Nichols WC, Seligsohn U, Zivelin A, Terry VH, Hertel CE, Wheatley MA, Moussalli MJ, Hauri HP, Ciavarella N, Kaufman RJ, Ginsburg D. 1998. Cell Apr 3;93(1):61-70). In addition, ERGIC-53 was reviewed as an attractive probe for studying numerous aspects of protein trafficking in the secretory pathway which is crucial for the elucidation and treatment of many inherited and acquired diseases, such as cystic fibrosis, Alzheimer's disease and viral infections (Hauri HP, Kappeler F, Andersson H, Appenzeller C. 2000 J Cell Sci Feb:113 Pt 4):587-96).

Cancer, infection, autoimmune disorder, hematopoietic disorder, wound healing disorders, inflammation, and Alzheimer's disease sbg101699 An embodiment of the invention is the use of Auto-immune sbgl016995IGBrecpt in the clearance of circulating diseases, allergy, autoantibodies and immune complexes. A close homologue and guillainof sbgl016995IGBrecpt is guinea pig Fc receptor for Barre syndrom immunoglobulin (Tominaga M, Sakata A, Ohmura T, Yamashita T, Koyama J, Onoue K, 1990. Biochem Biophys Res Commun Apr 30;168(2):683-9). IgG Fc-receptor polymorphisms have been reported recently in patients with guillain-Barre syndrome indicating the role of IgG Fcreceptor in the clearance of circulating autoantibodies and immune complexes (Vedeler CA, Raknes G, Myhr KM, _Nyland H. 2000 Neurology Sep 12;55(5):705-7).

sbgll51bS

REC

An embodiment of the invention is the use of sbgll51bSREC, a scavenger receptor, in the regulation of pathogenesis in atherosclerosis and the formation of foam cells in atherosclerotic lesions. A close homologue of sbgl 151bSREC is scavenger receptor class A type I and type II. Most of the scavenger receptors interacted with several structurally different ligands such as oxidized low density lipoprotein (Ox-LDL) and acetyl LDL. Several studies showed Ox-LDL was involved in the pathogenesis of atherosclerosis (Steinbrecher UP. 1999 Biochim Biophys Acta Jan 4;1436(3):279-98). In macrophages scattered in aortic walls without atherosclerotic lesions, scavenger receptor class A type I and type II (SRA) was detected weakly but consistently. In contrast, in atherosclerotic lesions, macrophages around the core region showed a strong immunoreactivity to SRA indicating the involvement of SRA in the formation of foam cells in atherosclerotic lesions (Nakata A, Nakagawa Y, Nishida M, Nozaki S, Miyagawa J, Nakagawa T, Tamura R, Matsumoto K, Kameda-Takemura K, Yamashita S and Matsuzawa Y. Arterioscler Thromb Vase Biol 1999 May;19(5):1333-9).

Atherosclerosis disease sbg139985 4ANK th r An embodiment of the invention is the use of sbg1399854ANK in protein-protein interactions and it may act by inhibiting protein of cyclin dependent kinase. The present invention contains both death domain and ankyrin repeat region. The death domain is involved in cell death signaling (Cleveland J. and Ihle J.N. 1995. Cell 81:479482).

Ankyrin repeats (ANK) are tandem repeat modules of about 33 amino acids. Many ankyrin repeat regions are known to be involved in protein-protein interaction (Svetlana Gorina and Nikola P. Pavletich; 1996 Science 274:1001-1005).

Cancer, infection, autoimmune disorder, hematopoietic disorder, wound healing disorders, and inflammation ^t Table IV. Quantitative, Tissue-specific mRNA expression detected using SybrMan 0Quantitative, tissue-specific, mRNA expression patterns of the genes were measured using SYBR- 1 Green Quantitative PCR (Applied Biosystems, Foster City, CA; see Schmittgen T.D. et al., SAnalytical Biochemistry 285:194-204, 2000) and human cDNAs prepared from various human 0 5 tissues. Gene-specific PCR primers were designed using the first nucleic acid sequence listed in the O Sequence List for each gene. The threshold cycle is defined as the fractional cycle number at \which the reporter fluorescence generated by cleavage of the probe reaches a threshold defined as C times the background. In cases sequence detection system software predicted more than one PCR product, Taqman was used for the specific PCR amplification as indicated under the specific genes.

tn In each gene's first subset table, two replicate measurements of gene of identification (GOI) mRNA were measured from various human tissues (column 3 and The average GOI mRNA copies of the c two replicates were made from each tissue RNA (column The average amount of 18S rRNA from each tissue RNA was measured (column 6) and used for normalization. To make each tissue with the same amount of 50 ng of 18S rRNA, the normalization factor (column 7) was calculated by dividing I 50 ng with the amount of 18S rRNA measured from each tissue (column The mRNA copies per ng of total RNA were obtained by multipling each GOI normalization factor and the average SmRNA copies (column8).

c Fold changes shown in each gene's second subset table were only calculated for disease tissues which have a normal counterpart. There are blanks in the fold change column for all samples that do not have counterparts. In addition, the fold change calculations are the fold change in the disease sample as compared to the normal sample. Accordingly, there will not be a fold change calculation next to any of the normal samples. For patient matched cancer pairs (colon, lung, and breast), each tumor is compared to its specific normal counterpart. When patient-matched normal/disease pairs do not exist, each disease sample was compared back to the average of all the normal samples of that same tissue type. For example, normal brain from the same patient that provided Alzheimer's brain is not applicable. Three normal brain samples and 4 Alzheimer's brain samples are used in the fold change. Three normal samples were averaged, and each of the Alzheimer's samples was compared back to that average.

Abbreviations ALZ Alzheimer's Disease CT CLONTECH (1020 East Meadow Circle Palo Alto, CA 94303-4230, USA) KC Sample prepared by GSK investigator COPD chronic obstructive pulmonary disease endo endothelial VEGF vascular endothelial growth factor bFGF basic fibroblast growth factor BM bone marrow osteo osteoblast OA osteoarthritis RA rheumatoid arthritis PBL peripheral blood lymphocytes PBMNC peripheral blood mononuclear cells HIV human immunodeficiency virus HSV Herpes simplex virus HPV human papilloma virus Gene Name sbg960509cbrecpt Lowest overall expression in normal and disease samples. Highest normal expression in the whole brain, fetal liver, and uterus. Highest disease expression in 2 of the lung tumor samples, one of the breast tumor samples, and one of the normal breast samples. Downregulation in 1 of 4 colon tumors implies an involvement in cancer of the colon. Downregulation in 2 of 4 AD brain samples as well as high expression in whole brain suggests an involvement in Alzheimer's disease. Downregulation in 3 of 3 COPD lung samples and downregulation in 4 of 4 asthmatic lung samples implicates this gene in COPD and asthma. Upregulation in 2 of 3 heart samples proposes roles in non-obstructive and obstructive DCM. Patterns difficult to interpret due to Cts 35. Moderate to low expression in immune cells. Moderate expression in OA and RA synovium.

Sample Ct Mean Mean Averag 18S 50 copies sbg960509cbrecpt (sample 1 GOI GOI e GOI rRNA ng/18S of and 2) copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 40, 40 0 0 0.00 3.06 16.34 0.00 Adipocytes Zenbio Subcutaneous 40, 40 0 0 0.00 0.96 52.36 0.00 Adipose Zenbio Adrenal Gland 40, 40 0 0 0.00 0.61 81.97 0.00 Clontech Whole Brain 33.26, 32.07 24.63 48.4 36.52 7.24 6.91 252.18 Clontech Fetal Brain Clontech 40, 40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 40, 40 0 0 0.00 2.17 23.04 0.00 Cervix 40, 40 0 0 0.00 2.42 20.66 0.00 Colon 40, 40 0 0 0.00 2.71 18.45 0.00 Endometrium 40, 40 0.81 0 0.41 0.73 68.21 27.63 Esophagus 40, 40 0 0 0.00 1.37 36.50 0.00 Heart Clontech 40, 40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40, 40 0 0 0.00 0.32 155.28 0.00 Ileum 40, 40 0 0 0.00 2.58 19.38 0.00 Jejunum 35.56, 34.42 6.66 12.71 9.69 6.60 7.58 73.37 Kidney 40, 40 0 0 0.00 2.12 23.58 0.00 Liver 40,40 0 0 0.00 1.50 33.33 0.00 Fetal Liver Clontech 33.46, 34.83 14.95 27.51 21.23 10.40 4.81 102.07 Lung 40, 40 0 0 0.00 2.57 19.46 0.00 Mammary Gland 40,40 21.94 10.06 16.00 13.00 3.85 61.54 Clontech Myometriumn 40,40 0 0 0.00 2.34 21.37 0.00 Omentum 40,40 0 0 0.00 3.94 12.69 0.00 Ovary 40,40 0 0 0.00 4.34 11.52 0.00 Pancreas 40,40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40, 40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 40,40 0 0 0.00 5.48 9.12 0.00 Placenta Clontech 40, 40 0.39 0 0.20 5.26 9.51 1.85 Prostate 40,40 0 0 0.00 3.00 16.67 0.00 Rectum 40,40 0 0 0.00 1.23 40.65 0.00 Salivary Gland 34.79, 40 10.31 0 5.16 7.31 6.84 35.26 Clontech Skeletal Muscle 40,40 0 0 0.00 1.26 39.68 0.00 Skin 40,40 0 0 0.00 1.21 41.32 0.00 Small Intestine 40,40 0 0 0.00 0.98 51.07 0.00 Clontech________ Spleen 40, 40 0 0 0.00 4.92 10.16 0.00 Stomach 35.8, 38.29 5.82 1.41 3.62 2.73 18.32 66.21 Testis Clontech 40, 40 0 0 0.00 0.57 87.87 0.00 Thymus Clontech 35.13, 35.08 8.48 8.75 8.62 9.89 5.06 43.55 Thyroid 40,40 0 0 0.00 2.77 18.05 0.00 Trachea Clontech 35.26, ND 7.9 ND 7.90 9.71 5.15 40.68 Urinary Bladder 40, ND 0 ND 0.00 5.47 9.14 0.00 Uterus 35.09, 33.87 8.67 17.4 13.04 5.34 9.36 122.05 genomic 26.62 1067.33___ b-actin 27.44 670.43 1.00E+05 19.22 100000 1.00E+05 19.38 100000 1.00E+04 22.78 1.OOE+04 20.52 10000 1.00E+03 26.45 1.00E+03 27.03 1000 1.00E+02 30.99 100 1.OOE+02 31.26 100 1.00E+01 40 1.00E+01 40 0 1.00E-00 40 1.00E-00 40 NTC 40 NTC 40 0 Sample Reg Ct Mean copies Sample Fold sbg960509cbrecpt number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populat total ion RNA colon normal GW98-167 21941 29.42 332.32 colon normal colon tumor GW98-166 21940 30.95 66.31 132.62 colon tumor -2.51 colon normal GW98-178 22080 31.32 53.01 106.02 colon normal colon tumor GW98-177 22060 30.57 83.1 166.20 colon tumor 1.57 colon normal GW98-561 23514 31.44 49.16 98.32 colon normal colon tumor GW98-560 23513 31.81 39.47 78.94 colon tumor -1.25 colon normal GW98-894 24691 29.44 164.69 329.38 colon normal colon tumor GW98-893 24690 34.42 8.18 16.36 colon tumor -20.13 lung normal GW98-3 20742 28.04 383.11 766.22 lung normal I lung tumor GW98-2 20741 34.22 9 .19 118.38 lung tumor -41.69 lung normal GW97- 179 20677 30.93 66.74 133.48 lung normal lung tumor GW97-178 20676 27.11 667.61 1335.22 lung tumor 10.00 lung normal GW98-165 21922 28.31 323.99 647.98 lung normal lung tumor GW98-164 21921 30.92 67.22 134.44 lung tumor -4.82 lung normal GW98-282 22584 31.76 40.67 181.34 lung normal lung tumor GW98-281 22583 29.61 148.67 297.34 lung tumor 3.66 breast normal GWOO-392 28750 27.64 487.44 487.44 breast normal breast tumor GWOO-391 28746 27.47 539.99 1079.98 breast tumor 2.22 breast normal GWOO-413 28798 33.36 15.44 15.44 breast normal breast tumor GWOO-412 28797 30.88 68.84 1137.68 breast tumor 8.92 breast normal GWOO- 27592-95 34.74 6.73 6.73 breast normal 235:238 breast tumor GWOO- 27588-91 33.73 12.41 12.41 breast tumor 1.84 231:234 breast normal GW98-621 23656 27.7 469.27 938.54 breast normal breast tumor GW98-620 23655 33.1 18.13 j36.26 breast tumor -25.88 brain normal BB99-542 25507 31.46 48.61 197.22 brain normal brain normal BB99-406 25509 34.17 9.52 19.04 brain normal brain normal BB99-904 25546 35.69 3.79 7.58 brain normal brain stage 5 ALZ BB99- 25502 40 0 0.00 brain stage 5 ALZ -41.28 874 brain stage 5 ALZ BB99- 25503 34.96 5.91 11.82 brain stage 5 ALZ -3.49 887 brain stage 5ALZ BB99- 25504 33.13 17.82 35.64 brain stage 5ALZ -1.16 862 brain stage 5 ALZ BB99- 25542 40 0 0.00 brain stage 5 ALZ -41.28 927 CT lung KC normal 29.53 155.88 311.76 CT lung lung 26 KC normal ____lung 26 lung 27 KC normal 39.2 0.46 0.46 lung 27 lung 24 KC COPD 40 0 0.00 lung 24 -104.07 lung 28 KC COPD 40 0 0.00 lung 28 -104.07 lung 23 KC COPD 34.81 6.44 16.44 lung 23 -16A1 lung 25 KC normal 40 0 0.00 lung asthmatic lung 29321 38.99 0.52 0.52 asthmatic lung -200.14 OD03 asthmatic lung 29323 33.69 12.65 25.30 asthmatic lung -4.11 0D03433___ asthmatic lung 29322 33.53 13.98 27.96 asthmatic lung -3.72 0D03397___ asthmatic lung 29325 34.27 8.96 17.92 asthmatic lung -5.81 0D04928______ endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 40 0 0.00 endo bFGF 0.00 heart Clontech normal 35.53 4.19 8.38 heart heart (T-lI ischemic 29417 34 10.5 21.00 heart T- 1 2.51 heart (T-14) non- 29422 31.16 58.24 116.48 heart T-14 13.90 obstructive DCM heart (T-3399) DCM 292 28351.7 1635.34 1heart T-3399 758 adenoid GW99-269 26162 31.52 46.93 93.86 adenoid tonsil GW98-280 22582 30.82 71.35 142.70 tonsil T cells PC00314 28453 34.36 8.47 16.94 T cells PBMNC 40 0 0.00 PBMNC monocyte 40 0 0.00 monocyte B cells PC00665 28455 40 0 0.00 B cells dendritic cells 28441 31.52 47.02 94.04 dendritic cells neutrophils 28440 36.13 2.91 2.91 neutrophils eosinophils 28446 40 0 0.00 eosinophils BM unstim 40 0 0.00 BM unstim BM stim 40 0 0.00 BM stim 0.00 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 40 0 0.00 chondrocytes OA Synoviumn IP12/01 29462 32.08 33.47 33.47 OA Synovium OA Synovium NP10/01 29461 31.43 49.5 99.00 OA Synovium OA Synovium NP57/00 28464 30.42 91.04 182.08 OA Synovium RA Synovium NPO3/01 28466 32.11 32.84 65.68 RA Synovium RA Synovium NP71/00 28467 31.07 61.51 123.02 RA Synovium RA Synovium NP45/00 28475 36.21 2.78 5.56 RA Synovium OA bone (biobank) 29217 31.49 47.85 47.85 OA bone (biobank) OA bone Sample 1 J. Emory 30.11 109.44 218.88 OA bone OA bone Sample 2 J. Emory 32.6 24.52 49.04 OA bone Cartilage (pool) Normal 32.09 33.26 66.52 Cartilage (pool) Cartilage (pool) OA 33.1 18.07 36.14 Cartilage (pool) -1.84 PBL unifected 28441 27.68 474.91 949.82 PBL unifected PBL HIV IIIB 28442 31.76 40.5 81.00 PBL HIV IIB -11.73 uninfected 29158 40 0 0.00 MRCS uninfected (100%) (100%) HSV strain F 29178 34.15 9.61 19.22 MRC5 HSV strain 19.22

F

W12 cells 29179 40 0 0.00 W12 cells Keratinocytes 29180 38.16 0.85 1.70 Keratinocytes B-actin control 27.02 707.5 genomic 26.1 1232.73 1.00E+05 18.64 100000 1.OOE+05 18.95 100000 1.00E+04 22.4 10000 1.00E+04 22.17 10000 1.00E+03 26.34 1000 1.OOE+03 25.94 1000 1.00E+02 31.03 100 1.00E+02 32.83 100 1.00E+01 33.21 1.00E+01 32.93 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 Gene Name sbg960509cbrecpt Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -2.51 colon tumor 1.57 colon tumor -1.25 colon tumor -20.13 lung tumor -41.69 lung tumor 10.00 lung tumor -4.82 lung tumor 3.66 breast tumor 2.22 breast tumor 8.92 breast tumor 1.84 breast tumor -25.88 brain stage 5 ALZ -41.28 brain stage 5 ALZ -3.49 brain stage 5 ALZ -1.16 brain stage 5 ALZ -41.28 lung 24 -104.07 lung 28 -104.07 lung 23 -16.16 asthmatic lung -200.14 asthmatic lung -4.11 asthmatic lung -3.72 asthmatic lung -5.81 endo VEGF 0.00 endo bFGF 0.00 heart T-1 2.51 heartT-14 13.90 heart T-3399 75.82 BM stim 0.00 osteo undif 0.00 Cartilage (pool) -1.84 PBL HIV IB -11.73 HSV strain F 19.22 Gene Name sbg614126complfH Moderate to low overall expression in normal and disease samples. Highest normal expression in liver and fetal liver. Lower (but still significant expression) is seen in the whole brain, ovary, and uterus. Highest disease expression in 2 of the breast tumor samples, one of the normal brain samples, one of the normal lungs, one of the OA synovium samples, and the HSV-infected cells. Upregulation in 1 of 4 colon tumors suggests a role in cancer of the colon. Downregulation in 2 of 4 lung tumors and upregulation in 1 of 4 breast tumors suggest roles in cancers of the lung and breast Downregulation in 3 of 3 COPD lung samples as well as downregulation in 4 of 4 asthmatic lungs implies an involvement in chronic obstructive pulmonary disease and asthma. Upregulation in 1 of 3 heart samples suggests a role in DCM. Upregulation in HSV implicates involvement in herpes simplex virus as a potential host factor. Moderate to low expression in immune cells, RA and OA synovium, bone, and chondrocytes.

Sample Ct sbg614126complfH (sample 1 IMean Mean Average 118S 50 copies SGOI GOI GOI rRNA I ng/18S I of and 2) copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) dIS0 ng total

RNA

Subcutaneous 40,40 0 0 0.00 3.06 16.34 0.00 Adipocytes Zenbio I

I

Subcutaneous 40, 40 0 0 0.00 0.96 52.36 0.00 Adipose Zenbio

I

Adrenal Gland 40, 40 0 0 0.00 0.61 81.97 0.00 Clontech Whole Brain 32.34, 31.88 46.5 61.71 54.11 7.24 6.91 373.65 Clontech Fetal Brain Clontech 40, 40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 40, 40 0 0 0.00 2.17 23.04 0.00 Cervix 40, 35.04 0 8.88 4.44 2.42 20.66 91.74 Colon 40, 40 0 0 0.00 2.71 18.45 0.00 Endometrium 40, 40 0 0 0.00 0.73 68.21 0.00 Esophagus 40, 40 0 0 0.00 1.37 36.50 0.00 Heart Clontech 40, 40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40, 39.79 0 0.48 0.24 0.32 155.28 37.27 Ileum 40, 36.32 0 4.04 2.02 2.58 19.38 39.15 Jejunum 33.25, 34.19 26.6 14.98 20.79 6.60 7.58 157.50 Kidney 40, 40 0 0 0.00 2.12 23.58 0.00 Liver 28.77, 28.81 417.4 407.38 412.39 1.50 33.33 13746.

33 Fetal Liver Clontech 29.63, 29.5 246.38 266.67 256.53 10.40 4.81 1233.2 19 Lung 40, 40 0 0 0.00 2.57 19.46 0.00 Mammary Gland 34.19, 40 14.9 0 7.45 13.00 3.85 28.65 Clontech Myometrium 35.76, 40 5.7 0 2.85 2.34 21.37 60.90 Omentum 36.04, 33.62 4.81 21.16 12.99 3.94 12.69 164.78 Ovary 34.29, 32.95 14.02 31.93 22.98 4.34 11.52 264.69 Pancreas 40, 40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 38.98, 35.35 0.79 7.32 4.06 1.57 31.85 129.14 Parotid Gland 34.58, 33.83 11.74 18.68 15.21 5.48 9.12 138.78 Placenta Clontech 35.73, 35.66 5.82 6.06 5.94 5.26 9.51 56.46 Prostate 40, 40 0 0 0.00 3.00 16.67 0.00 Rectum 40, 40 0.38 0 0.19 1.23 40.65 7.72 Salivary Gland 40, 40 0.3 0 0.15 7.31 6.84 1.03 Clontech I I Skeletal Muscle 40, 40 0 0.28 0.14 1.26 39.68 5.56 Clontech Skin 40, 40 0 0.33 0.17 1.21 41.32 6.82 Small Intestine 40, 40 0 0 0.00 0.98 51.07 0.00 Clontech

I

Spleen 40, 40 0 0 0.00 4.92 10.16 0.00 Stomach 40, 36 0 4.92 2.46 2.73 18.32 45.05 Testis Clontech 40, 40 0 0 0.00 0.57 87.87 0.00 Thymus Clontech 40, 37.06 0 2.56 1.28 9.89 5.06 6.47 Thyroid 40, 40 0 0.31 0.16 2.77 18.05 2.80 Trachea Clontech 40,40 0.28 0 0.14 9.71 5.15 0.72 Urinary Bladder 40, 34.13 0 15.53 7.77 5.47 9.14 70.98 Uterus 33.21, 32.79 27.27 35.32 31.30 5.34 9.36 293.02 genomic 26.93 b-actin 27.55 1.OOE+05 20.07 1.OOE+05 20.14 1.00E+04 23.43 1.00E+04 23.34 10000 1.00E+03 26.84 1.00E+03 27.02 1000___ 1.00E+02 31.72 1.00E+02 31.32 1.00E+01 33.78 1.OOE+01 35.79 1.00E-00 40 0 1.00E-00 40 NTC 40 NTC 40 Sample Reg Ct Mean copies Sample Fold sbg614126complfH number GOI of Change in (GSK copies mRNA Disease identifier detecte Populatio d/50 ng n total RNA colon normal GW98- 21941 34.6 13.63 27.26 colon normal 167 colon tumor GW98-166 21940 35.71 7.35 14.70 colon tumor -1.85 colon normal GW98- 22080 40 0 0.00 colon normal colon tumor GW98-177 22060 39.81 0.75 1.50 colon tumor 1.50 colon normal GW98- 23514 38.61 1.45 2.90 colon normal colon tumor GW98-560 23513 34.84 11.95 23.90 colon tumor 8.24 colon normal GW98- 24691 39.05 1.14 2.28 colon normal 894 colon tumor GW98-893 24690 40 0 0.00 colon tumor -2.28 lung normal GW98-3 20742 35.78 7.04 14.08 lung normal lung tumor GW98-2 20741 40 0 0.00 lung tumor -14.08 lung normal GW97-179 20677 33.99 19.21 38.42 lung normal lung tumor GW97-178 20676 40 0.49 0.98 lung tumor -39.20 lung normal GW98-165 21922 39.63 0.82 1.64 lung normal lung tumor GW98-164 21921 38.89 1.24 2.48 lung tumor 1.51 lung normal GW98-282 22584 40 0 0.00 lung normal lung tumor GW98-281 22583 40 0 0.00 lung tumor 0.00 breast normal GWOO- 28750 32.71 39.28 39.28 breast normal 392 breast tumor GWOO-391 28746 31.65 70.89 141.78 breast tumor 3.61 breast normal GWOO- 28798 35.83 6.88 6.88 breast normal 413 1 breast tumor GWOO-412 28797 33.17 30.3 60.60 breast tumor 8.81 breast normal GWO0- 27592-95 36.73 4.16 4.16 breast normal 235:238 breast tumor GW0O- 27588-91 35.98 6.33 6.33 breast tumor 1.52 231:234 breast normal GW98- 23656 37.38 2.89 5.78 breast normal 621 breast tumor GW98-620 23655 34.95 11.23 22.46 breast tumor 3.89 brain normal BB99-542 25507 32.26 50.34 100.68 brain normal brain normal BB99-406 25509 40 0.57 1.14 brain normal brain normal BB99-904 25546 34.68 13.04 26.08 brain normal brain stage 5 ALZ 25502 40 0 0.00 brain stage 5 -42.63 BB99-874

ALZ

brain stage 5 ALZ 25503 35.87 6.73 13.46 brain stage 5 -3.17 BB99-887

ALZ

brain stage 5 ALZ 25504 39.2 1.05 2.10 brain stage 5 -20.30 BB99-862

ALZ

brain stage 5 ALZ 25542 40 0 0.00 brain stage 5 -42.63 BB99-927

ALZ

CT lung KC normal 39.4 0.93 1.86 CT lung lung 26 KC normal lung 26 lung 27 KC normal 40 0 0.00 lung 27 lung 24 KC COPD 40 0 0.00 lung 24 -0.62 lung 28 KC COPD 40 0 0.00 lung 28 -0.62 lung 23 KC COPD 40 0 0.00 lung 23 -0.62 lung 25 KC normal 40 0 0.00 lung asthmatic lung 29321 36.52 4.68 4.68 asthmatic lung 7.55 OD03112 asthmatic lung 29323 40 0 0.00 asthmatic lung -0.62 OD03433 asthmatic lung 29322 40 0 0.00 asthmatic lung -0.62 OD03397

I

asthmatic lung 29325 38.18 1.85 3.70 asthmatic lung 5.97 0104928 endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 40 0 0.00 endo bFGF 0.00 heart Clontech normal 40 0 0.00 heart heart T- 1 ischemic 29417 40 0 0.00 heart T- 1 0.00 heart (T-14) non- 29422 40 0 0.00 heart T-14 0.00 obstructive

DCMI_

heart (T-3399) DCM 29426 36.03 6.13 12.26 heart T-3399 12.26 adenoid GW99-269 26162 34.08 18.19 36.38 adenoid tonsil GW98-280 22582 37.46 2.77 5.54 tonsil T cells PC00314 28453 40 0 0.00 T cells PBMNC 140 0 0.00 PBMNC monocyte 140 0 0.00 monocyte B cells PC00665 28455 34.56 13.99 27.98 B cells dendritic cells 28441 40 0 0.00 dendritic cells neutrophils 28440 33.76 21.85 21.85 neutrophils eosinophils 28446 40 0 0.00 eosinophils BM unstim 40 0 0.00 BM unstim BM stim 40 0 0.00 BM stim 0.00 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 34.25 16.55 41.38 chondrocytes OA Synovium IP12101 29462 40 0 0.00 OA Synovium OA Synovium NPIO/01 29461 40 0 0.00 QA Synovium OA Synovium NP57/00 28464 33.1 31.54 63.08 OA Synovium RA Synovium NP03/01 28466 40 0 0.00 RA Synovium RA Synovium NP71/00 28467 40 0 0.00 RA Synovium RA Synovium NP45/00 28475 40 0 0.00 RA Synovium OA bone (biobank) 29217 40 0 0.00 QA bone (biobank) OA bone Sample I J. Emory 40 0 0.00 OA bone OA bone Sample 2 J. Emory 40 0 0.00 QA bone Cartilage (pool) Normal 40 0 0.00 Cartilage (pool) Cartilage (pool) QA 40 0 0.00 Cartilage (pool) 0.00 PBL unifected 28441 36.12 5.84 11.68 PBL unifected PBLHTVI B 28442 36.1 5.9 11.80 PBLHIV IIIB 1.01 uninfected 29158 40 0 0.00 (100%) uninfected 1 (100%)_ MRCS HSV strain F 29178 31.83 64.08 128.16 MRC5HSV 128.16 strain F W12 cells 29179 40 0 0.00 W12 cells Keratinocytes 29180 40 0 0.00 Keratinocytes B-actin control 27.26 820.77 genomic 26.18 1496.25 1.OOE+05 19.13 100000 1.OOE+05 19.38 100000 1.OOE+04 22.56 10000 1.00E+04 22.67 10000 1.OOE+03 26.01 1000 1.00E+03 26.44 1000 1.OOE+02 30.93 100 1.00E+02 30.1 100 1.00E+O1 38.59 1.OOE+01 _33.26 1.OOE-00 40 0 1.00E-00 0 NTC 40 0 Gene Name sbg614126complfH Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -1.85 colon tumor 1.50 colon tumor 8.24 colon tumor -2.28 lung tumor -14.08 lung tumor -39.20 lung tumor 1.51 lung tumor 0.00 breast tumor 3.61 breast tumor 8.81 breast tumor 1.52 breast tumor 3.89 brain stage 5 ALZ -42.63 brain stage 5 ALZ -3.17 brain stage 5 ALZ -20.30 brain stage 5 ATLZ -42.63 lung 24 -0.62 lung 28 -0.62 lung 23 -0.62 asthmatic lung 7.55 asthmatic lung -0.62 asthmatic lung -0.62 asthmatic lung 5.97 endo VEGF 0.00 endo bFGF 0.00_ heart T- 1 0.00 heart T-14 0.00 heart T-3399 12.26 BM stim 0.00 osteo undif 0.00 Cartilage (pool) 0.00 PBL FHIV IIIB 1.01 HSV strain F 128.16 Gene Name sbgl20703RNase Moderate to low overall expression in normal and disease samples. Highest normal expression in whole brain and salivary gland. Moderate expression in the fetal liver and the thymus. Highest disease expression in 2 of the normal lung samples, one of the lung tumor samples, the normal cartilage pool, and the HSV-infected MRC5 cells. Upregulation in 1 of 4 colon tumors suggests a role in cancer of the colon. Downregulation in 2 of 4 lung tumor samples suggests possible implication in lung cancer. Upregulation in 2 of 4 breast tumors implies an involvement in cancers of the breast. Downregulation in 3 of 3 COPD lung samples implies an involvement in COPD.

Upregulation in 3 of 3 heart samples implicates this gene in diseases of the heart such as DCM and ischemia. High expression in the OA and RA synovium and the OA bone samples suggests a possible involvement in osteoarthritis and rheumatoid arthritis. Upregulation in HSV implicates this gene in herpes simplex virus as a potential host factor. Moderate to low expression in immune cells.

Sample Ct (sample Mean Mean Averag 18S 50 copies sbgl207O3RNase 1 and 2) GOT GOI e GOI rRNA ng/18S of.

copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/S0 ng total

RNA

Subcutaneous 40, 36.24 0 2.54 1.27 3.06 16.34 20.75 Adipocytes Zenbio

I

Subcutaneous 36.58, 40 2.07 0 1.04 0.96 52.36 54.19 Adipose Zenbio

I

Adrenal Gland 40, 40 0.22 0 0.11 0.61 81.97 9.02 Clontech

I

Whole Brain 28.62, 28.6 245.21 247.41 246.31 7.24 6.91 1701.04 Clontech Fetal Brain Clontech 40,40 0.3 0 0.15 0.48 103.95 15.59 Cerebellum 40,40 0.29 0 0.15 2.17 23.04 3.34 Clontech

I

Cervix 35.3, 40 4.45 0 2.23 2.42 20.66 45.97 Colon 40,40 0.26 0 0.13 2.71 18.45 2.40 Endometrium 40, 38.38 0 0.7 0.35 0.73 68.21 23.87 Esophagus 36.11, 37.01 2.74 1.6 2.17 1.37 36.50 79.20 Heart Clontech 40,40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40,40 0 0 0.00 0.32 155.28 0.00 Ileum 39.31, 36.07 0.4 2.8 1.60 2.58 19.38 31.01 Jejunum 34.13,39.51 8.98 0.36 4.67 6.60 7.58 35.38 Kidney 40,40 0.48 0 0.24 2.12 23.58 5.66 Liver 34.4, 36.04 7.64 2.86 5.25 1.50 33.33 175.00 Fetal Liver Clontech 31.46, 31.39 44.65 46.4 45.53 10.40 4.81 218.87 Lung 34.21, 35.61 8.59 3.71 6.15 2.57 19.46 119.65 Mammary Gland 34.9, 35.65 5.67 3.6 4.64 13.00 3.85 17.83 ClonteehI Myometriurn 40, 38.99 0 0.49 0.25 2.34 21.37 5.24 Omentum 38.39, 34.35 0.7 7.89 4.30 3.94 12.69 54.51 Ovary 35, 33.21 5.34 15.64 10.49 4.34 11.52 120.85 Pancreas 40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 32.22, 33.49 28.28 13.18 20.73 5.48 9.12 189.14 Placenta Clontech 37, 39.59 1.6 0.34 0.97 5.26 9.51 9.22 Prostate 35.03, 35.75 5.23 3.4 4.32 3.00 16.67 71.92 Rectum 38.25, 40 0.76 0.21 0.49 1.23 40.65 19.72 Salivary Gland 30.01, 29.73 106.25 125.78 116.02 7.31 6.84 793.54 Clontech Skeletal Muscle 40, 39.16 0.41 0.44 0.43 1.26 39.68 16.87 Clontech Sin 37.21, 35.01 1.42 5.31 13.37 1.21 41.32 139.05 Small Intestine 40,40 0 0.19 0.10 0.98 51.07 4.85 ClontechI Spleen 35.4, 35.9 4.2 3.11 3.66 4.92 10.16 37.14 Stomach 36.12, 40 2.73 0.21 1.47 2.73 18.32 26.92 Testis Clontech 40, 40 0 0 0.00 0.57 87.87 0.00 Thymus Clontech 31.88, 31.42 34.61 45.62 40.12 9.89 5.06 202.81 Thyroid 40, 35.22 0 4.67 2.34 2.77 18.05 42.15 Trachea Clontech 35.38, 37.52 4.26 1.17 2.72 9.71 5.15 13.98 Urinary Bladder 38.77, 40 0.56 0.31 0.44 5.47 9.14 3.98 Uterus 33.66, 37.55 11.93 1.16 6.55 5.34 19.36 61.28 genomic 25.78 1342.66 b-actin 27.27 551.42 1.00E+05 19.03 100000 1.00E+05 19.08 100000 1.OOE+04 22.28 10000 L.00E+04 22.27 10000 1.00E+03 25.85 1000 1.OOE+03 25.6 1000 1.00E+02 30.44 100 1.0O+02 29.33 100 1.OE+01 34.4 1.OOE+01 34.48 L.00E-00 1.OOE-00 NTC 40 1 NTC 40 0 Sample sbgl2O7O3RNase Reg Ct Mean copies of Sample Fold number GOI mRNA Change (GSK copies detected/ in identifie 50 ng Disease r) total Populati RNA on colon normal GW98-167 21941 29.03 142.85 285.70 colon normal colon tumor GW98-166 21940 28.31 226.87 453.74 colon tumor 1.59 colon normal GW98-178 22080 33.08 10.78 21.56 colon normal colon tumor GW98-177 22060 29.33 118.09 236.18 colon tumor 10.95 colon normal GW98-561 23514 30.02 76.09 152.18 colon normal colon tumor GW98-560 23513 30.42 58.89 117.78 colon tumor -1.29 colon normal GW98-894 24691 29.07 139.29 278.58 colon normal colon tumor GW98-893 24690 30.3 63.5 127.00 colon tumor -2.19 lung normal GW98-3 20742 26.86 574.4 1148.80 lung normal lung tumor GW98-2 20741 30.07 73.89 147.78 lung tumor -7.77 lung normal GW97-179 20677 29.74 90.79 181.58 lung normal lung tumor GW97-178 20676 27.63 351.24 702.48 lung tumor 3.87 lung normal GW98-165 21922 26.63 663.94 1327.88 lung normal lung tumor GW98-164 21921 29.38 114.52 229.04 lung tumor -5.80 lung normal GW98-282 22584 30 77.02 154.04 lung normal lung tumor GW98-281 22583 29.64 97.04 194.08 lung tumor 1.26 breast normal GWOO-392 28750 29.08 138.57 138.57 breast normal breast tumor GWOO-391 28746 28.77 169.53 339.06 breast tumor 2.45 breast normal GWOO-413 28798 32.72 13.55 13.55 breast normal breast tumor GWOO-412 28797 31.01 40.4 80.80 breast tumor 5.96 breast normal GWOO- 27592- 34.39 4.68 4.68 breast normal 235:238 breast tumor GWOO- 27588- 31.4 31.48 31.48 breast tumor 6.73 231:234 breast normal GW98-621 23656 28.54 195.6 391.20 breast normal breast tumor GW98-620 23655 30.37 60.84 121.68 breast tumor -3.21 brain normal BB99-542 25507 32.94 11.79 23.58 brain normal brain normal BB99-406 25509 32.22 18.66 37.32 brain normal brain normal BB99-904 25546 32.3 17.71 35.42 brain normal brain stage 5 ALZ BB99- 25502 32.82 12.76 25.52 brain stage 5 -1.26 874 brain stage 5 ALZ BB99- 25503 30.31 63.18 126.36 brain stage 5 3.94 ALZ brain stage 5 ALZ BB99- 25504 31.42 31.08 62.16 brain stage 5 1.94 862

ALZ____

brain stage 5 ALZ BB99- 25542 33.35 9.08 18.16 brain stage 5 -1.77 927

ALZ

CT lung KC normal 30.41 59.49 118.98 CT lung lung 26 KC normal lung 26 lung 27 KC normal 37.69 0.57 0.57 lung 27 lung 24 KC COPD 40 0 0.00 lung 24 -40.17 lung 28 KC COPD 40 0 0.00 lung 28 -40.17 lung 23 KC COPD 40 0 0.00 lung 23 -40.17 lung 25 KC normal 36.86 0.97 0.97 lung asthmatic lung OD03112 29321 33.08 10.79 10.79 asthmatic lung -3.72 asthmatic lung OD03433 29323 29.94 80.31 160.62 asthmatic lung 4.00 asthmatic lung OD03397 29322 29.79 87.94 175.88 asthmatic lung 4.38 asthmatic lung OD04928 29325 30.08 73.39 146.78 asthmatic lung 3.65 endo cells KC control 40 0.13 0.13 endo cells endo VEGF KC 40 0 0.00 endo VEGF -0.13 endo bFGF KC 40 0.12 0.12 endobFGF -1.08 heart Clontech normal 34.66 3.95 7.90 heart____ heart T-1 ischemic 29417 30.43 58.48 116.96 heart T-1 14.81 heart (T-14) non- 29422 30.3 63.76 127.52 heart T-14 16.14 obstructive DCM heart (T-3399) DCM 29426 31.14 37.27 74.54 heart T-3399 9.44 adenoid GW99-269 26162 33.15 10.31 20.62 adenoid tonsil GW98-280 22582 30.26 65.22 130.44 tonsil T cells PC00314 28453 33.29 9.45 18.90 T cells PBMNC 40 0 0.00 PBMNC monocyte 40 0 0.00 monocyte B cells PC00665 28455 32.25 18.35 36.70 B cells dendritic cells 28441 30.52 55.34 110.68 dendritic cells neutrophils 28440 31.61 27.61 27.61 neutrophils eosinophils 28446 33.2 10.01 20.02 eosinophils BM unstim 40 0 0.00 BM unstim BM stim 40 0 0.00 BM stim 0.00 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 10.00 osteo undif chondrocytes 29.65 96.25 240.63 chondrocytes OA Synoviumn EP12/01 29462 28.59 190.09 190.09 OA Synovium OA Synovium NP 10101 29461 29.06 140.66 281.32 OA Synovium OA Synovium NP57/00 28464 28.38 216.61 433.22 OA Synovium RA Synovium NP03/01 28466 29.43 111 222.00 RA Synovium RA Synoviurn NP71/00 28467 28.35 220.48 1440.96 RA Synoviumn RA Synovium NP45/00 28475 28.7 176.79 353.58 RA Synovium OA bone (biobank) 29217 30.6 52.6 52.60 OA bone ______(biobank) OA bone Sample I J. 29.64 97.1 194.20 OA bone Emory OA bone Sample 2 J. 30.85 44.71 189.42 OA bane Cartilage (pool) Normal 28.07 264.86 529.72 Cartilage (pool) Cartilage (pool) OA 30.47 56.97 113.94 Cartilage -4.65 PBL unifected 28441 33.41 8.73 17.46 PBL unifected PBLHBIVIB 28442 32.1 20.17 40.34 PBLIV IIB 2.31 uninfected (100%) 29158 31.09 38.5 77.00 uninfected HSV strain F 29178 28.24 237.46 1474.92 MRC5 HSV 6.17 strain W 12 cells 29179 28.83 162.45 1324.90 W 12 cells Keratinocytes 29180 29.21 127.89 1255.78 Keratinocytes B-actin control 26.99 528.52 genomic 1229.15 1.OOE+05 18.76 100000 1.OOE+05 19.03 100000 1.OOE+04 22.01 10000 1.OO13+04 22.05 10000 1.OOE+03 1000 1.00E+03 __25.68 1000 i.OOE+02 30.57 100 1.OOE+02 30.32 100 1.00E+01 32.24 10 1.OO13+01 __40 L.00E-00 0 1.0013-00 __40 NTC 0 Gene Name sbgl2O7O3RNase Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.59 colon tumor 10.95 colon tumor -1.29 colon tumor -2.19 lung tumor -7.77 lung tumor 3.87 lung tumor -5.80 lung tumor 1.26 breast tumor 2.45 breast tumor 5.96 breast tumor 6.73 breast tumor -3.21 brain stage 5 ALZ -1.26 brain stage 5 ALZ 3.94 brain stage 5 ALZ 1.94 brain stage 5 ALZ -1.77 lung 24 -40.17 lung 28 -40.17 lung 23 -40.17 asthmatic lung -3.72 asthmatic lung 4.00 asthmatic lung 4.38 asthmatic lung 3.65 endo VEGF -0.13 endo bFGF -1.08 heart T-1 14.81 heart T-14 16.14 heart T-3399 9.44 BM stim 0.00 osteo undif 0.00 Cartilage (pool) -4.65 PBL HIV IIB 2.31 HSV strain F 6.17 Gene Name sbg98530TS Moderate overall expression in normal and disease samples. Highest normal expression in whole brain, endometrium, and testis. Moderate expression in normal heart, skeletal muscle, and esophagus. Shows expression in most of the GI tract samples as well as the female reproductive tract samples. Highest disease expression in one of the colon tumor samples, all 3 of the heart samples, and the chondrocytes. Data predominantly shows a muscle-specific pattern of expression.

Upregulation in 1 of 4 colon tumors and upregulation in 2 of 4 breast tumors implies an involvement in cancers of the colon and breast Downregulation in 3 of 3 COPD samples implies a role in chronic obstructive pulmonary disease. Downregulation in HSV implicates involvement in herpes simplex virus as a potential host factor. Moderate to low overall expression in immune cells.

High expression in chondrocytes and OA and RA synovium suggests possible involvement in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Averag 185 50 copies sbg98530TS 1 and 2) GOI GOI e GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sampl (ng) detecte 1) e 2) d/50 ng total

RNA

Subcutaneous 40, 36.35 0 4.22 2.11 3.06 16.34 34.48 Adipocytes Zenbio Subcutaneous Adipose 35.78, 40 5.89 0 2.95 0.96 52.36 154.19 Zenbio Adrenal Gland 40, 40 0 0 0.00 0.61 81.97 0.00 Clontech__ Whole Brain Clontech 26.63, 26.42 1253.02 1414.2 1333.61 7.24 6.91 9210.01 Fetal Brain Clontech 40, 37.33 0 2.38 1.19 0.48 103.95 123.70 Cerebellum Clontech 35.9, 40 5.5 0 2.75 2.17 23.04 63.36 Cervix 33.47, 34.27 22.86 14.26 18.56 2.42 20.66 383.47 Colon 34.49, 34.05 12.58 16.28 14.43 2.71 18.45 266.24 Endometrium 33.28, 32.94 25.41 31.15 28.28 0.73 68.21 1929.06 Esophagus 33.61, 32.9 21.02 31.85 26.44 1.37 36.50 964.78 Heart Clontech 33.32, 33.03 24.91 29.42 27.17 1.32 37.88 1028.98 Hypothalamus 40, 40 0 0 0.00 0.32 155.28 0.00 Ileum 35.89, 33.37 5.53 24.14 14.84 2.58 19.38 287.50 Jejunum 31.55, 31.42 70.2 75.71 72.96 6.60 7.58 552.69 Kidney 40, 35.5 0 6.96 3.48 2.12 23.58 82.08 Liver 34.29, 33.63 14.07 20.78 17.43 1.50 33.33 580.83 Fetal Liver Clontech 32.16, 32.92 49.02 31.52 40.27 10.40 4.81 193.61 Lung 40, 35.78 0 2.95 2.57 19.46 57.30 Mammary Gland 31'42, 32.08 75.62 51.54 63.58 13.00 3.85 244.54 Clontech Myometrium 32.93, 32.03 31.21 52.84 42.03 2.34 21.37 897.97 Omentum 35.21,40 8.23 0 4.12 3.94 12.69 52.22 Ovary 35.36, 35.51 7.53 6.89 7.21 4.34 11.52 83.06 Pancreas 40,40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40, 37.54 0 2.11 1.06 1.57 31.85 33.60 Parotid Gland 31.67,31.01 65.33 96.46 80.90 5.48 9.12 738.09 Placenta Clontech 33.13, 32.05 27.88 52.3 40.09 5.26 9.51 381.08 Prostate 35.03,40 9.13 5.22 7.18 3.00 16.67 119.58 Rectum 40, 35.19 0 8.32 4.16 1.23 40.65 169.11 Salivary Gland 32.41, 34.06 42.32 16.15 29.24 7.31 6.84 199.97 Clontech Skeletal Muscle 33.93, 33.76 17.41 19.28 18.35 1.26 39.68 727.98 Clontech Skin 40,40 0 0 0.00 1.21 41.32 0.00 Small Intestine 34.11 11.73 15.7 13.72 0.98 51.07 700.46 Clontech Spleen 36.08,40 4.94 0.37 2.66 4.92 10.16 26.98 Stomach 40, 40 0 0 0.00 2.73 18.32 0.00 Testis Clontech 35.54, 33.26 6.79 25.83 16.31 0.57 87.87 1433.22 Thymus Clontech 33.66, 34.12 20.35 15.62 17.99 9.89 5.06 90.93 Thyroid 40, 35.46 0 7.12 3.56 2.77 18.05 64.26 Trachea Clontech 32.08, 31.84 51.54 59.21 55.38 9.71 5.15 285.14 Urinary Bladder 34.75, 36.99 10.8 2.91 6.86 5.47 9.14 62.66 Uterus 31.79, 32.2 60.97 47.95 54.46 5.34 9.36 509.93 genomic 26.8 1133.17 b-actin 27.6 706.62 1.00E+05 19.53 100000 1.00E+05 19.54 100000 1.OOE+04 22.8 10000 1.00E+04 23.02 10000 1.00E+03 26.14 1000 1.OOE+03 26.59 1000 1 L.00E+02 31.41 100 1.OOE+02 30.97 100 1.OOE+01 40 0 1.ooE+01 35.24 1.OOE-00 40 0 1.OOE-00 40 0 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies Sample Fold sbg98530TS number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populat total ion

RNA

colon normal GW98-167 21941 26.26 1792.89 3585.78 colon normal colon tumor GW98-166 21940 26.2 1856.22 3712.44 colon tumor 1.04 colon normal GW98-178 22080 27.25 986.8 1973.60 colon normal colon tumor GW98-177 22060 26.7 1369.12 2738.24 colon tumor 1.39 colon normal GW98-561 23514 27.55 821.35 1642.70 colon normal colon tumor GW98-560 23513 24.64 4748.96 9497.92 colon tumor 5.78 colon normal GW98-894 24691 27.27 971.87 1943.74 colon normal colon tumor GW98-893 24690 25.35 3093.47 6186.94 colon tumor 3.18 lung normal GW98-3 20742 27.02 1133.68 2267.36 lung normal lung tumor GW98-2 20741 27.26 981.94 1963.88 lung tumor -1.15 lung normal GW97-179 20677 29.14 315.07 630.14 lung normal lung tumor GW97-178 20676 28.15 571.76 1143.52 lung tumor 1.81 lung normal GW98-165 21922 27.86 682.2 1364.40 lung normal lung tumor GW98-164 21921 27.45 871.19 1742.38 lung tumor 1.28 lung normal GW98-282 22584 28.12 581.74 1163.48 lung normal lung tumor GW98-281 22583 29.32 283.71 567.42 lung tumor -2.05 breast normal GWOO-392 28750 27.85 687.38 687.38 breast normal breast tumor GWOO-391 28746 26.61 1444.19 2888.38 breast tumor 4.20 breast normal GWOO-413 28798 28.43 483.03 483.03 breast normal breast tumor GWOO-412 28797 25.49 2836.66 5673.32 breast tumor 11.75 breast normal GWOO- 27592-95 32.26 48.29 48.29 breast normal 235:238 breast tumor GWOO- 27588-91 29.07 328.46 328.46 breast tumor 6.80 231:234 breast normal GW98-621 23656 26.82 1279.07 2558.14 breast normal breast tumor GW98-620 23655 26.8 1289.27 2578.54 breast tumor 1.01 brain normal BB99-542 25507 29.03 337.63 675.26 brain normal brain normal BB99-406 25509 29.19 305.6 611.20 brain normal brain normal BB99-904 25546 30.44 144.55 289.10 brain normal brain stage 5 ALZ BB99- 25502 28.47 471.8 943.60 brain stage 5 ALZ 1.80 874 1 1 brain stage 5 ALZ BB99- 25503 27.3 955.52 1911.04 brain stage5 ALZ 3.64 887 1 1 1 brain stage 5 ALZ BB99- 25504 27.42 891.77 1783.54 brain stage 5 ALZ 3.40 862 brain stage 5 ALZ BB99- 25542 29.31 285.16 570.32 brain stage 5 ALZ 1.09 927 CT lung KC normal 27.96 643.88 1287.76 CT lung lung 26 KC normal 35.82 5.66 5.66 lung 26 lung 27 KC normal 40 0 0.00 lung 27 lung 24 KC COPD 40 0 0.00 lung 24 -325.52 lung 28 KC COPD 35.3 7.73 7.73 lung 28 -42.11 lung 23 KC COPD 36.67 3.39 3.39 lung 23 -96.02 lung 25 KC normal 35.11 8.67 8.67 lung asthmatic lung OD03112 29321 31.01 102.08 102.08 asthmatic lung -3.19 asthmatic lung OD03433 29323 29.76 216.81 433.62 asthmatic lung 1.33 asthmatic lung OD03397 29322 29.83 208.08 416.16 asthmatic lung 1.28 asthmatic lung OD04928 29325 30.37 150.17 300.34 asthmatic lung -1.08 endo cells KC control 37.54 2 2.00 endo cells endo VEGF KC 35.77 5.83 5.83 endo VEGF 2.92 endo bFGF KC 40 0 0.00 endo bFGF -2.00 heart Clontech normal 26.09 1982.44 3964.88 heart heart T-1 ischemic 29417 24 6956.27 13912.5 heart T-1 3.51 4 heart (T-14) non- 29422 24.55 5010.03 10020.0 heart T-14 2.53 obstructive DCM 6 heart (T-3399) DCM 29426 24.05 6766.57 13533.1 heart T-3399 3.41 4 adenoid GW99-269 26162 30.56 134.11 268.22 adenoid tonsil GW98-280 22582 27.94 651.01 1302.02 tonsil T cells PC00314 28453 29.8 212.45 424.90 T cells PBMNC 33.01 30.69 30.69 PBMNC monocyte 33.42 23.9 47.80 monocyte B cells PC00665 28455 33.52 22.59 45.18 B cells dendritic cells 28441 29.07 329.58 659.16 dendritic cells neutrophils 28440 30.39 149 149.00 neutrophils eosinophils 28446 35.41 7.25 14.50 eosinophils BM unstim 34.24 14.65 14.65 BM unstim BM stim 36.61 3.51 3.51 BM stim -4.17 osteo dif 30.55 135.33 135.33 osteo dif 3.02 osteo undif 32.38 44.88 44.88 osteo undif chondrocytes 25.35 3089.54 7723.85 chondrocytes OA Synovium IP12/01 29462 28.75 398.53 398.53 OA Synovium OA Synovium NP10/01 29461 27.04 1119.77 2239.54 OA Synovium OA Synovium NP57/00 28464 28.85 375.92 751.84 OA Synovium RA Synovium NP03/01 28466 28.14 574.66 1149.32 RA Synovium RA Synovium NP71/00 28467 27.58 806.11 1612.22 RA Synovium RA Synovium NP45/00 28475 28.04 611.1 1222.20 RA Synoviumn OA bone (biobank) 29217 30.25 161.3 161.30 OA bone (biobank) OA bone Sample 1 J. Emory 31.24 89.29 178.58 OA bone OA bone Sample 2 J. Emory 30.98 104.34 208.68 OA bone Cartilage (pool) Normal 29.86 204.47 408.94 Cartilage (pool) Cartilage (pool) OA 29.37 275.09 550.18 Cartilage (pool) 1.35 PBL unifected 28441 26.45 1598.39 3196.78 PBL unifected PBL HIV IIIB 28442 27.57 814.58 1629.16 PBL IHIV IIIB -1.96 uninfected 29158 25.13 3539.95 7079.90 MRC5 uninfected (100%) (100%) HSV strain F 29178 30.49 139.89 279.78 MRC5 HSV strain -25.31

F

W12 cells 29179 26.72 1359.04 2718.08 W12 cells Keratinocytes 29180 26.41 1633.77 3267.54 Keratinocytes B-actin control 27.87 678.8 genomic 26.9 1214.71 1.OOE+05 19.86 100000 1.00E+05 19.82 100000 1.00E+04 23.15 10000 1.00E+04 23.21 10000 1.00E+03 26.62 1000 1.OOE+03 26.79 1000 1.OOE+02 31.2 100 1.OOE+02 32.2 100 1.00E+01 40 0 1.00E+01 34.53 1.00E-00 40 0 1.OOE-00 40 0 NTC 40 0 Gene Name sbg98530TS Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.04 colon tumor 1.39 colon tumor 5.78 colon tumor 3.18 lung tumor -1.15 lung tumor 1.81 lung tumor 1.28 lung tumor -2.05 breast tumor 4.20 breast tumor 11.75 breast tumor 6.80 breast tumor 1.01 brain stage 5 ALZ 1.80 brain stage 5 ALZ 3.64 brain stage 5 ALZ 3.40 brain stage 5 ALZ 1.09 lung 24 -325.52 lung 28 -42.11 lung 23 -96.02 asthmatic lung -3.19 asthmatic lung 1.33 asthmatic lung 12 asthmatic lung -1.08 endo VEGF 2.92 endo bFGF heart T-I heart T-14 heart T-3399 34 BM stim -4.17 osteo undif 3.02 Cartilage (pool) 1.35 PBL HIV MIB -1.96 HSV strain F -25.31 Gene Name sbg5639l7RDP Moderate to low overall expression in normal and disease samples. Hfighest normal expression in testis liver, trachea, and whole brain. Shows good expression in most of the GI tract samples.

Highest disease expression in T cells, B cells, neutrophils, and eosinophils. Upregulation in 1 of 4 breast tumors implies involvement in cancer of the breast. Downregulation in 3 of 3 COPD lungs suggests an involvement in chronic obstructive pulmonary disease. Downregulation in the ischemnic heart sample implicates this gene in ischemic heart disease. Downregulation in the VEGF and bFGF-treated endothelial cells suggests a role in angiogenesis. Upregulation in HSV implicates involvement in herpes simplex virus as a potential host factor.

Sample Ct (sample Mean Mean Avera 18S 5o copies sbg563917RDP 1 and 2) GOI GOI ge rRNA ng/18S of copies copies GOI (ng) rRNA juRNA (sample (sample Copies (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 35.34, 40 3.66 0 1.83 3.06 16.34 29.90 Adipocytes Subcutaneous Adipose 40, 40 0 0.00 0.96 52.36 0.00 Zenbio Adrenal Gland Clontech 40, 40 0 0 0.00 0.61 81.97 10.00 Whole Brain Clontech 30.09, 30.01 91.85 96.8 94.33 7.24 6.91 651.42 Fetal Brain Clontech 40, 40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 35.19,40 4.03 0 2.02 2.17 23.04 46.43 Cervix 36.08, 40 2.33 0 1.17 12.42 20.66 24.07 Colon 36.07, 35.1 2.35 4.24 3.30 12.71 18.45 60.79 Endometriumn 35.01, 40 4.49 0 2.25 0.73 68.21 1153.14 Esophagus 34.94,40 4.68 0 2.34 1.37 36.50 85.40 Heart Clontech 40,40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40, 40 0 0 10.00 0.32 155.28 0.00 fleum 35.24, 40 3.89 0 11.95 2.58 19.38 37.69 Jejunumi 35.37, 33.35 3.6 12.44 8.02 6.60 7.58 160.76 Kidney 40, 34.97 0 4.6 2.30 2.12 23.58 154.25 Liver 33.51, 34.6 11.25 5.78 8.52 1.50 33.33 1283.83 Fetal Liver Clontech 33.19, 35.54 13.75 3.25 8.50 10.40 4.81 140.87 Lung 34.32 6.84 2.28 4.56 2.57 19.46 88.72 Mammary Gland 40, 35.14 0 4.15 2.08 13.00 3.85 7.98 Myometriurnm 40, 40 0 0.09 0.05 2.34 21.37 0.96 Omentum 36.17, 33.01 2.2 15.32 8.76 3.94 12.69 111.17 Ovary 40,40 0 0 0.00 4.34 11.52 0.00 Pancreas 40,40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40,40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 35.43, 39.81 3.46 0.24 1.85 5.48 9.12 16.88 Placenta Clontech 33.7, 35.45 10.02 3.42 6.72 5.26 9.51 63.88 Prostate 40,40 0 0 0.00 3.00 16.67 0.00 Rectum 40,40 0 0 0.00 1.23 40.65 0.00 Salivary Gland 34.89,40 4.83 0 2.42 7.31 6.84 16.52 Clontech Skeletal Muscle 40,40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 40,40 0 0 0.00 1.21 41.32 0.00 Small Intestine 40,40 0 0 0.00 0.98 51.07 0.00 Clontech____ Spleen 35.01,33.36 4.48 12.38 8.43 4.92 10.16 85.67 Stomach 33.38, 34.18 12.18 7.48 9.83 2.73 18.32 180.04 Testis Clontech 34.25, 32.86 7.17 16.84 12.01 0.57 87.87 1054.92 Thymus Clontech 32.14, 33.25 26.17 13.24 19.71 9.89 5.06 99.62 Thyroid 40, 40 0 0.09 0.05 2.77 18.05 0.81 TracheaClontech 31.41,31 41.04 52.65 46.85 9.71 5.15 241.22 Urinary Bladder 40, 35.05 0 4.38 2.19 5.47 9.14 20.02 Uterus 33.77, 33.41 9.62 12 10.81 5.34 9.36 101.22 genomic 26.54 813.56 genomic b-actin 27.39 1.00E+05 18.71 100000 1.00E+05 18.92 100000 1.00E+04 22.44 10000______ 1.00E+04 22.11 10000 1.00E+03 26.05 1.00E+03 26.11 1.00E+02 30.4 1.00E+02 30.17 100 1.00E+01 33.87 1.00E+01 33.26 1.00E-00 40 1.00E-00 40 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies Sample Fold sbg563917RDP number GOI of Change in (GSK copies mRNA Disease identifier detecte Population d/50 ng total RNA colon normal GW98-167 21941 30.39 148.35 296.70 colon normal colon tumor GW98-166 21940 30.93 110.14 220.28 colon tumor -1.35 colon normal GW98-178 22080 32.93 36.71 73.42 colon normal colon tumor GW98-177 22060 34.8 13.09 26.18 colon tumor -2.80 colon normal GW98-561 23514 31.41 84.68 169.36 colon normal colon tumor GW98-560 23513 32.09 158.33 116.66 colon tumor -1.45 colon normal GW98-894 24691 30.02 1182.15 364.30 colon normal colon tumor GW98-893 24690 31.12 99.26 198.52 colon tumor -1.84 lung normal GW98-3 20742 28.4 443.99 887.98 lung normal lung tumor GW98-2 20741 33.59 25.44 50.88 lung tumor -17.45 lung normal GW97-179 20677 28.63 391.85 783.70 lung normal lung tumor GW97-178 20676 29.16 292.08 584.16 lung tumor -1.34 lung normal GW98-165 21922 29.13 296.8 593.60 lung normal lung tumor GW98-164 21921 30.22 163.43 326.86 lung tumor -1.82 lung normal GW98 -282 22584 31.71 7 1.72 143.44 lung normal lung tumor GW98-281 22583 31.74 70.77 141.54 lung tumor -1.01 breast normal GWOO-392 28750 31.49 81.02 81.02 breast nor-mal breast tumor GWOO-391 28746 33.58 25.62 51.24 breast tumor -1.58 breast normal GWOO-413 28798 35.07 11.31 11.31 breast normal breast tumor GWOO-412 28797 31.99 61.52 123.04 breast tumor 10.88 breast normal GWO0- 27592-95 35.63 8.3 8.30 breast normal 235:238 breast tumor GWDO- 275 88-91 34.33 16.97 16.97 breast tumor 2.04 231:234 breast normal GW98-621 23656 32.07 58.95 117.90 breast normal breast tumor GW98-620 23655 32.71 41.33 82.66 breast tumor 1.43 brain normal BB99-542 25507 30.16 168.86 337.72 brain normal brain normal BB99-406 25509 31.12 99.35 198.70 brain normal brain normal BB99-904 25546 31.14 98.44 196.88 brain normal brain stage 5 ALZ BB99- 25502 33.16 32.39 64.78 brain stage 5 ALZ -3.77 874 brain stage 5 ALZ BB99- 25503 29.32 1267.28 534.56 brain stage 5 ALZ 2.19 887 brain stage 5 ALZ BB99- 25504 30.36 1150.72 301.44 brain stage 5 ALZ 1.23 862 brain stage 5 ALZ BB99- 25542 30.1 174.01 348.02 brain stage 5 AI.Z 1.42 .927 CT lung KC normal 31.06 102.88 205.76 CT lung_____ lung 26 KG normal 32.15 56.21 56.21 lung 26 lung 27 KG normal 35.96 6.92 6.92 lung 27 lung 24 KG COPD 40 0 0.00 lung 24 -70.34 lung 28 KG COPD 36.21 6.05 6.05 lung 28 -11.63 lung 23 KG COPD 34.83 12.87 12.87 lung 23 -5.47 lung 25 KG normal 34.89 12.45 12.45 lung asthmatic lung 0D03 112 29321 32.57 44.76 44.76 asthmatic lung -1.57 asthmatic lung 0D03433 29323 32.4 49.04 98.08 asthmatic lung 1.39 asthmatic lung 0D03397 29322 31.79 68.64 1137.28 asthmatic lung 1.95 asthmatic lung 0D04928 29325 31.34 88.11 176.22 asthmatic lung 2.51 endo cells KCcontrol 35.77 7.68 7.68 endo cells I endo VEGF KG 40 0 0.00 endo VEGF 1-7.68 endo bFGF KC 40 0 0.00 endo bFGF -7.68 heart Clontech normal 31.09 100.75 201.50 heart heart T- ischemic 29417 34.75 13.46 26.92 heart T-1 -7.49 heart (T-14) non- 29422 33.69 24.17 48.34 heart T-14 -4.17 obstructive DCM heart (T-3399) DCM 29426 33.48 27.16 54.32 heart T-3399 -3.71 adenoid GW99-269 26162 30.49 140.7 281.40 adenoid tonsil GW98-280 22582 30.07 177.32 354.64 tonsil T cells PC00314 28453 27.79 622.1 1244.20 T cells PBMNC 36.19 6.11 6.11 PBMNC monocyte 33.24 30.91 61.82 monocyte B cells PC00665 28455 26.37 1355.2 2710.40 B cells dendritic cells 28441 28.69 378.62 757.24 dendritic cells neutrophils 28440 23.28 7420.47 7420.47 neutrophils eosinophils 28446 25.33 2408.94 4817.88 eosinophils BM unstim 32.24 53.57 53.57 BM unstim BM stim 31.92 64.05 64.05 BM stim 1.20 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 37.59 2.82 7.05 chondrocytes OA Synovium 1P12/01 29462 31.77 69.48 69.48 OA Synovium OA Synovium NPl0/01 29461 31.16 96.93 193.86 OA Synovium OA Synovium NP57/00 28464 30.84 115.69 231.38 OA Synovium RA Synovium NPO3/01 28466 30.96 108.37 216.74 RA Synovium RA Synovium NP/ 1/00 28467 29.2 285.91 571.82 RA Synovium RA Synovium NP45/00 28475 29.87 198.12 396.24 RA Synovium OA bone (biobank) 29217 29.67 220.64 220.64 OA bone (biobank) OA bone Sample 1 J. Emory 30.54 136.41 272.82 OA bone OA bone Sample 2 J. Emory 29.38 259.07 518.14 OA bone Cartilage (pool) Normal 31.34 87.88 175.76 Cartilage (pool) Cartilage (pool) OA 32.9 37.23 74.46 Cartilage (pool) -2.36 PBL unifected 28441 30.55 135.85 271.70 PBL unifected PBL HIV IB 28442 31.02 104.8 209.60 PBL HIV IIB -1.30 uninfected 29158 35.11 11.06 22.12 MRCS uninfected (100%) (100%) HSV strain F 29178 29.63 226.14 452.28 MRC5 HSV strain 20.45

F

W12 cells 29179 37.87 2.42 4.84 W12 cells Keratinocytes 29180 36.14 6.26 12.52 Keratinocytes B-actin control 27.14 887.42 genomic 26.16 1520.17 1.00E+05 19.22 100000 1.00E+05 19.2 100000 1.00E+04 22.49 10000 1.00E+04 22.62 10000 1.00E+03 26.23 1000 1.00E+03 26.05 1000 I1.00E+02 30.26 100 1.OOE+02 31.03 100 1.00E+01 38.68 1.OOE+01 33.47 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 Gene Name sbg563917RDP Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -1.35 colon tumor -2.80 colon tumor -1.45 colon tumor -1.84 lung tumor -17.45 lung tumor -1.34 lung tumor -1.82 lung tumor -1.01 breast tumor -1.58 breast tumor 10.88 breast tumor 2.04 breast tumor -1.43 brain stage 5 ALZ -3.77 brain stage 5 ALZ 2.19 brain stage 5 ALZ 1.23 brain stage 5 ALZ 1.42 lung 24 -70.34 lung 28 -11.63 lung 23 -5.47 asthmatic lung -1.57 asthmatic lung 1.39 asthmatic lung 1.95 asthmatic lung 2.51 endo VEGF -7.68 endo bFGF -7.68 heart T- 1 -7.49 heart T-14 -4.17 heart T-3399 -3.71 BM stim 1.20 osteo undif 0.00 Cartilage (pool) -2.36 PBL HIV IIIB -1.30 HSV strain F 20.45 Gene Name sbg618069LRR Low overall expression in normal and disease samples. Highest normal expression in whole brain, fetal brain, cerebellum, and thymus. Highest disease expression in one of the colon tumor samples, one of the lung tumor samples, and the uninfected PBL cells. Downregulation in 2 of 4 colon tumors suggests a role in cancer of the colon. Upregulationiin 1 of 4 lung tumors and upregulation in 2 of 4 breast tumors suggest roles in cancers of the lung and breast. Downregulation in 3 of 3 COPD lung samples implicates a role for this gene in COPD. Upregulation in the stimulated bone marrow. Downregulation in an HIV-infected cell line as well as moderate expression in immune cels suggests an involvement in HIV. Upregulation in HSV implicates involvement in herpes.

simplex virus as a potential host factor.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg6l8O69LRR I and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 35.24, 34.33 4.38 7.65 6.02 3.06 16.34 98.28 Adipocytes Zenbio Subcutaneous Adipose 40, 40 0 0.08 0.04 0.96 52.36 2.09 Zenbio Adrenal Gland Clontech 39.9, 38.74 0.13 0.51 0.32 0.61 81.97 26.23 Whole Brain Clontech 27.02,26.51 673.36 916.93 795.15 7.24 6.91 5491.33 Fetal Brain Clontech 40,40 0.13 6.01 3.07 0.48 103.95 319.13 Cerebellum Clontech 32.15, 32.13 28.98 29.44 29.21 2.17 23.04 673.04 Cervix 40, 40 0 0 0.00 2.42 20.66 0.00 Colon 36.53, 39.88 1.98 0.25 1.12 2.71 18.45 20.57 Endometrium 37.98,40 0.82 0.19 0.51 0.73 68.21 34.45 Esophagus 38.86, 40 0.48 0.15 0.32 1.37 36.50 11.50 Heart Clontech 34.17, 34.72 8.41 6.03 7.22 1.32 37.88 273.48 Hypothalamus 40, 40 0 0.07 0.04 0.32 155.28 5.43 Ileum 40,40 0.17 0.11 0.14 2.58 19.38 2.71 Jejunum 33.07, 34.34 16.52 7.58 12.05 6.60 7.58 91.29 Kidney 36.05,40 2.67 0.21 1.44 2.12 23.58 33.96 Liver 38.72, 40 0.52 0.61 0.57 1.50 33.33 18.83 Fetal Liver Clontech 33.28, 36.35 14.52 2.22 8.37 10.40 4.81 40.24 Lung 40,40 0.13 0.08 0.11 2.57 19.46 2.04 Mammary Gland 40, 34.19 0 8.33 4.17 13.00 3.85 16.02 Clontech Myometrium 40, 40 0.28 0 0.14 2.34 21.37 2.99 Omentum 35.01, 35.36 5.04 4.07 4.56 3.94 12.69 57.80 Ovary 34.24,40 8.07 0.26 4.17 4.34 11.52 47.98 Pancreas 40,40 0.11 0.13 0.12 0.81 61.80 7.42 Head of Pancreas 40,40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 34.01, 34.28 9.31 7.9 8.61 5.48 9.12 78.51 Placenta Clontech 40, 40 0 0.07 0.04 5.26 9.51 0.33 Prostate 40, 39.13 0.15 0.4 0.28 3.00 16.67 4.58 Rectum 40, 39.55 0.21 0.31 0.26 1.23 40.65 10.57 Salivary Gland 32.35, 33.08 25.74 16.45 21.10 7.31 6.84 144.29 Clontech Skeletal Muscle 34.78, 40 5.81 0.27 3.04 1.26 39.68 120.63 Clontech Skin 40,40 0 0 0.00 1.21 41.32 0.00 Small Intestine 40, 40 0.16 0 0.08 0.98 51.07 4.09 Clontech Spleen 35.59, 40 3.53 0.59 2.06 4.92 10.16 20.93 Stomach 36.73,40 1.76 0.11 0.94 2.73 18.32 17.12 Testis Clontech 37.91, 40 0.86 0.1 0.48 0.57 87.87 42.18 Thymus Clontech 30.22, 29.94 94.88 112.23 103.56 9.89 5.06 523.53 Thyroid 35.15,40 4.62 0 2.31 2.77 18.05 41.70 Trachea Clontech 33.49, 34.21 12.75 8.22 10.49 9.71 5.15 53.99 Urinary Bladder 40,40 0.09 0.08 0.09 5.47 9.14 0.78 Uterus 35.26, 33.03 4.31 16.97 10.64 5.34 9.36 99.63 genomic 26.04 1229.54 b-actin 27.25 584.19 1.OOE+05 19.09 100000 1.OOE+05 19.04 100000____ 1.OOE+04 22.35 10000 1.00E+04 22.35 10000 1.00E+03 26.07 1000 1.00E+03 26.26 1000 1.00E+02 30.64 100 1.00E+02 30.38 100 1.00E+01 34.04 1.00E+O1 33.52 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 NTC 40 Sample Reg Ct Mean copies Sample Fold sbg618069LRR number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populati total on colon normal GW98-167 21941 29.52 176.51 353.02 colon normal colon tumor GW98-166 21940 33.45 18.5 37.00 colon tumor -9.54 colon normal GW98-178 22080 31.82 47.14 94.28 colon normal colon tumor GW98-177 22060 29.68 160.67 321.34 colon tumor 3.41 colon normal GW98-561 23514 30.33 110.78 221.56 colon normal colon tumor GW98-560 23513 33.11 22.39 44.78 colon tumor -4.95 colon normal GW98-894 24691 28.1 396.95 793.90 colon normal colon tumor GW98-893 24690 26.93 779.99 1559.98 colon tumor 1.96 lung normal GW98-3 20742 30.41 105.78 211.56 lung normal lung tumor GW98-2 20741 26.28 1128.28 2256.56 lung tumor 10.67 lung normal GW97-179 20677 29.28 201.91 403.82 lung normal lung tumor GW97-178 20676 28.35 345.36 690.72 lung tumor 1.71 lung normal GW98-165 21922 28.42 331.95 663.90 lung normal lung tumor GW98-164 21921 30.98 76.05 152.10 lung tumor -4.36 lung normal GW98-282 22584 34.15 12.36 24.72 lung normal lung tumor GW98-281 22583 32.08 40.6 81.20 lung tumor 3.28 breast normal GWOO-392 28750 29.67 161.68 161.68 breast normal breast tumor GWOO-391 28746 28.98 239.65 479.30 breast tumor 2.96 breast normal GWOO-413 28798 31.78 48.04 48.04 breast normal breast tumor GWOO-412 28797 29.69 159.55 319.10 breast tumor 6.64 breast normal GWOO- 27592-95 34.18 12.14 12.14 breast normal 235:238 breast tumor GWOO- 27588-91 29.2 211.28 211.28 breast tumor 17.40 231:234 breast normal GW98-621 23656 29.72 157.4 314.80 breast normal breast tumor GW98-620 23655 31.12 70.17 140.34 breast tumor -2.24 brain normal BB99-542 25507 30.81 83.89 167.78 brain normal brain normal BB99-406 25509 31.02 74.28 148.56 brain normal brain normal BB99-904 25546 31.39 60.08 120.16 brain normal brain stage 5 ALZ BB99- 25502 32.54 31.07 62.14 brain stage 5 ALZ -2.34 874____ brain stage 5 ALZ BB99- 25503 30.65 92.1 184.20 brain stage 5 ALZ 1.27 brain stage 5 ALZ BB99- 25504 31.68 50.92 101.84 brain stage 5 ALZ -1.43 brain stage 5 ALZ BB99- 25542 31.39 60.36 120.72 brain stage 5 ALZ -1.21 CT lung KC normal 30.47 101.87 203.74 CT lung lung 26 KC normal lung 26 lung 27 KC normal 39.27 0.65 0.65 lung 27 lung 24 KC COPD 40 0 0.00 lung 24 -68.13 lung 28 KC COPD 37.38 1.93 1.93 lung 28 -35.30 lung 23 KC COPD 34.28 11.47 11.47 lung 23 -5.94 lung 25 KC normal 40 0 0.00 lung asthmatic lung OD03112 29321 33.17 21.73 21.73 asthmatic lung -3.14 asthmatic lung OD03433 29323 32.35 34.64 69.28 asthmatic lung 1.02 asthmatic lung OD03397 29322 30.83 83.1 166.20 asthmatic lung 2.44 asthmatic lung OD04928 29325 30.94 77.99 155.98 asthmatic lung 2.29 endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 40 0 0.00 endo bFGF 0.00 heart Clontech normal 30.52 99.45 198.90 heart heart (T-1 ischemic 29417 28.78 270.18 540.36 heart T-1 2.72 heart (T-14) non- 29422 29.62 166.76 333.52 heart T-14 1.68 obstructive DCM heart (T-3399) DCM 29426 30.05 129.76 259.52 heart T-3399 1.30 adenoid GW99-269 26162 29.05 230.93 461.86 adenoid tonsil GW98-280 22582 29.77 152.22 304.44 tonsil T cells PC00314 28453 31.6 53.48 106.96 T cells PBMNC 39.8 0.48 0.48 PBMNC monocyte 40 0 0.00 monocyte B cells PC00665 28455 31.56 54.77 109.54 B cells dendritic cells 28441 34.09 12.8 25.60 dendritic cells neutrophils 28440 34.03 13.21 13.21 neutrophils eosinophils 28446 40 0 0.00 eosinophils BM unstim 40 0 0.00 BM unstim BM stim 35.71 5.04 5.04 BM stim 5.04 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 33.5 17.89 44.73 chondrocytes OA Synovium IP12/01 29462 32.24 37.02 37.02 OA Synovium OA Synovium NP10/01 29461 27.95 434.95 869.90 OA Synovium OA Synovium NP57/00 28464 30.9 79.82 159.64 OA Synovium RA Synovium NPO3/01 28466 31.79 47.9 95.80 RA Synovium RA Synovium NP71/00 28467 33.06 23.05 46.10 RA Synovium RA Synovium NP45/00 28475 32.76 27.41 54.82 RA Synovium OA bone (biobank) 29217 32.02 42.02 42.02 OA bone (biobank) OA bone Sample 1 J. Emory 31.32 62.63 125.26 OA bone OA bone Sample 2 J. Emory 33.13 22.24 44.48 OA bone Cartilage (pool) Normal 30.76 86.51 173.02 Cartilage (pool) Cartilage (pool) OA 33.13 22.15 44.30 Cartilage (pool) -3.91 PBL unifected 28441 26.78 847.01 1694.02 PBL unifected PBL HIV IIIB 28442 28.21 374.26 748.52 PBL HIV IB -2.26 MRCS uninfected 29158 40 0 0.00 MRCS uninfected (100%) (100%) HSV strain F 29178 31.26 64.96 129.92 MRCS HSV strain 129.92

F

W12 cells 29179 40 0 0.00 W12 cells Keratinocytes 29180 39.77 0.49 0.98 Keratinocytes B-actin control 27.18 675.17 genomic 25.96 1358.6 1.00E+05 18.58 100000 1.00E+05 18.53 100000 1.00E+04 22.04 10000 1.00E+04 22.1 10000 1.00E+03 25.85 1000 1.00E+03 26.11 1000 1.00E+02 34.02 100 1.00E+02 30.53 100 1.00E+01 32.98 1.00E+01 40 0 1.00E-00 40 0 1.00E-00 38.21 1 NTC 40 0 Gene Name sbg618069LRR Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -9.54 colon tumor 3.41 colon tumor -4.95 colon tumor 1.96 lung tumor 10.67 lung tumor 1.71 lung tumor -4.36 lung tumor 3.28 breast tumor 2.96 breast tumor 6.64 breast tumor 17.40 breast tumor -2.24 brain stage 5 ALZ -2.34 brain stage 5 ALZ 1.27 brain stage 5 ALZ -1.43 brain stage 5 ALZ -1.21 lung 24 -68.13 lung 28 -35.30 lung 23 -5.94 asthmatic lung -3.14 asthmatic lung 1.02 asthmatic lung 2.44 asthmatic lung 2.29 endo VEGF 0.00 endo bFGF 0.00 heart T-1 2.72 heart T-14 1.68 heart T-3399 1.30 BM stim 5.04 osteo dif 0.00 Cartilage (pool) -3.91 PBL HIV mIB -2.26 HSV strain F 129.92 Gene Name sbg934114Relaxin Low overall expression in normal and disease samples. Highest normal expression in testis, liver, and whole brain. Highest disease expression in 3 of the normal lung samples, one of the normal tumor samples, the HSV-infected MRC5 cells, the adenoid, and the T cells. Highest disease expression in 2 of the normal lung samples, one of the lung tumor samples, 1 of the normal breast samples, I of the breast tumor samples, and the uninfected PBL samples. Downregulation in 1 of 4 colon tumors and downregulation in 2 of 4 lung tumors imply roles in cancers of the colon and lung.

Downregulation in 3 of 3 COPD lung samples and upregulation in 3 of 4 asthmatic lung samples implicates this gene in COPD and asthma. Upregulation in 2 of 3 heart samples proposes roles in non-obstructive and obstructive DCM. Downregulation in the OA cartilage pool and low expression in RA and OA synovium, OA bone, and chondrocytes suggests an involvement in osteoarthritis and rheumatoid arthritis. Downregulation in an HIV-infected primary cell line suggests an involvement in HIV. Upregulation in HSV implicates involvement in herpes simplex virus as a potential host factor.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg934114Relaxin 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 37.4, 40 5.41 0 2.71 3.06 16.34 44.20 Adipocytes Zenbio Subcutaneous Adipose 40, 40 0.73 0 0.37 0.96 52.36 19.11 Zenbio Adrenal Gland Clontech 40, 40 0.73 0.69 0.71 10.61 81.97 58.20 Whole Brain Clontech 33.52, 34.72 47.76 24.26 36.01 7.24 6.91 248.69 Fetal Brain Clontech 39.51,40 1.65 0.86 1.26 0.48 103.95 130.46 Cerebellum Clontech 40,39.84 0.99 1.37 1.18 2.17 23.04 27.19 Cervix 40, 40 1.05 0 0.53 2.42 20.66 10.85 Colon 40, 37.31 0 5.7 2.85 2.71 18.45 52.58 Endometrium 40, 40 0 0 0.00 0.73 68.21 0.00 Esophagus 40, 40 0 0 0.00 1.37 36.50 0.00 Heart Clontech 38.11, 40 3.63 1.31 2.47 1.32 37.88 93.56 Hypothalamus 40,40 0 1.06 0.53 0.32 155.28 82.30 Ileum 40, 36.79 0 7.62 3.81 2.58 19.38 73.84 Jejunum 35.14, 35.9 19.25 12.54 15.90 6.60 7.58 120.42 Kidney 40, 40 0 0 0.00 2.12 23.58 0.00 Liver 37.25, 35.17 5.88 18.92 12.40 1.50 33.33 413.33 Fetal Liver Clontech 40, 37.38 0.73 5.47 3.10 10.40 4.81 14.90 Lung 37.07,40 6.52 0 3.26 2.57 19.46 63.42 Mammary Gland 40,40 0 0 0.00 13.00 3.85 0.00 Clontech Myometrium 37.95, 40 3.98 0 1.99 2.34 21.37 42.52 Omentum 36.24,37.04 10.39 6.63 8.51 3.94 12.69 107.99 Ovary 35.29, 36.26 17.66 10.28 13.97 4.34 11.52 160.94 Pancreas 39.48, 40 1.69 0 0.85 0.81 61.80 52.22 Head of Pancreas 36.17, 39.82 10.79 1.39 6.09 1.57 31.85 193.95 Parotid Gland 40,38.66 0 2.67 1.34 5.48 9.12 12.18 Placenta Clontech 40, 36.57 0 8.63 4.32 5.26 9.51 41.02 Prostate 36.91, 40 7.14 0 3.57 3.00 16.67 59.50 Rectum 40,37.34 0 5.61 2.81 1.23 40.65 114.02 Salivary Gland 40,40 0 0 0.00 7.31 6.84 0.00 Clontech

I

Skeletal Muscle 40, 39.45 0 1.71 0.86 1.26 39.68 33.93 Clontech Skin 39.2, 40 1.98 0 0.99 1.21 41.32 40.91 Small Intestine 40,40 0 0 0.00 0.98 51.07 0.00 Clontech Spleen 36, 40 11.84 0 5.92 4.92 10.16 60.16 Stomach 35.48, 39.19 15.9 1.98 8.94 2.73 18.32 163.74 Testis Clontech 40, 36.09 0 11.27 5.64 0.57 87.87 495.17 Thymus Clontech 34.34, 36.66 30.03 8.2 19.12 9.89 5.06 96.64 Thyroid 40,40 0 0 0.00 2.77 18.05 10.00 Trachea Clontech 40,37.8 0 4.33 2.17 9.71 5.15 11.15 Urinary Bladder 40, 40 0 0 0.00 5.47 9.14 0.00 Uterus 37.11, 35.16 6.36 18.96 12.66 5.34 9.36 118.54 genomic 27.61 1307.98 b-actin 27.15 1697.68 1.00E+05 19.88 100000 I .OOE+05 20.05 100000 1.OOE+04 24.01 10000 1.00E+04 23.92 10000 1.00E+03 27.98 1000 l.OOE+03 27.6 1000 1.OOE+02 32.89 100 1.OOE+02 32.2 100 1.OOE+01 36.1 1.00E+01 1.OOE-00 1.OOE-00 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies Sample Fold sbg934114Relaxin number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populati total on

RNA

colon normal GW98-167 21941 36.1 22.33 44.66 colon normal colon tumor GW98-166 21940 36.47 18.37 36.74 colon tumor -1.22 colon normal GW98-178 22080 35.7 27.58 55.16 colon normal colon tumor GW98-177 22060 38.05 7.98 15.96 colon tumor -3.46 colon normal GW98-561 23514 33.57 84.85 169.70 colon normal colon tumor GW98-560 23513 37.66 9.8 19.60 colon tumor -8.66 colon normal GW98-894 24691 36.39 19.09 38.18 colon normal colon tumor GW98-893 24690 36.43 18.74 37.48 colon tumor -1.02 lung normal GW98-3 20742 32.48 150.6 301.20 lung normal lung tumor GW98-2 20741 36.65 16.64 33.28 lung tumor -9.05 lung normal GW97-179 20677 33.22 102.07 204.14 lung normal lung tumor GW97-178 20676 32.31 164.63 329.26 lung tumor 1.61 lung normal GW98-165 21922 32.08 185.96 371.92 lung normal lung tumor GW98-164 21921 35.14 37.09 74.18 lung tumor -5.01 lung normal GW98-282 22584 36.41 18.93 37.86 lung normal lung tumor GW98-281 22583 35.24 35.13 70.26 lung tumor 1.86 breast normal GWOO-392 28750 34.04 66.25 66.25 breast normal breast tumor GWOO-391 28746 37.9 8.61 17.22 breast tumor -3.85 breast normal GWOO-413 28798 36.36 19.44 19.44 breast normal breast tumor GWOO-412 28797 36.79 15.49 30.98 breast tumor 1.59 breast normal GWOO- 27592-95 36.91 14.52 14.52 breast normal 235:238 breast tumor GW00- 27588-91 35.43 31.71 31.71 breast tumor 2.18 231:234 1 breast normal GW98-621 23656 36.26 20.51 41.02 breast normal breast tumor GW98-620 23655 35.76 26.68 53.36 breast tumor 1.30 brain normal BB99-542 25507 37.99 8.21 16.42 brain normal brain normal BB99-406 25509 40 1.41 2.82 brain normal brain normal BB99-904 25546 40 0 0.00 brain normal brain stage 5 ALZ BB99- 25502 38.65 5.82 11.64 brain stage 5 ALZ 1.81 874 brain stage 5 ALZ BB99- 25503 37 13.9 27.80 brain stage 5 ALZ 4.33 887 brain stage 5 ALZ BB99- 25504 37.4 11.24 22.48 brain stage 5 ALZ 3.51 862_ brain stage 5 ALZ BB99- 25542 38 8.19 16.38 brain stage 5 ALZ 2.55 927 CT lung KC normal 35.32 33.59 67.18 CT lung lung 26 KC normal 37.02 13.72 13.72 lung 26 lung 27 KC normal 40 0 0.00 lung 27 lung 24 KC COPD 39.97 2.78 2.78 lung 24 -7.81 lung 28 KC COPD 40 0 0.00 lung 28 -21.71 lung 23 KC COPD 39.06 4.67 4.67 lung 23 -4.65 lung 25 KC normal 38.61 5.92 5.92 lung asthmatic lung OD03112 29321 36.02 23.31 23.31 asthmatic lung 1.07 asthmatic lung OD03433 29323 34.12 63.36 126.72 asthmatic lung 5.84 asthmatic lung OD03397 29322 33.99 68.06 136.12 asthmatic lung 6.27 asthmatic lung OD04928 29325 33.77 76.08 152.16 asthmatic lung 7.01 endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 38.16 7.54 7.54 endo bFGF 7.54 heart Clontech normal 40 0 0.00 heart heart (T-I ischemic 29417 40 1.36 2.72 heart T- 1 2.72 heart (T-14) non- 29422 36.31 20.01 40.02 heart T-14 40.02 obstructive DCM heart (T-3399) DCM 29426 37.17 12.7 25.40 heart T-3399 25.40 adenoid GW99-269 26162 33.33 96.07 192.14 adenoid tonsil GW98-280 22582 34.86 42.85 85.70 tonsil T cells PC00314 28453 33.48 88.65 177.30 T cells PBMNC 40 0 0.00 PBMNC monocyte 40 0 0.00 monocyte B cells PC00665 28455 32.44 153.68 307.36 B cells dendritic cells 28441 35.78 26.47 52.94 dendritic cells neutrophils 28440 36.18 21.43 21.43 neutrophils eosinophils 28446 39.2 4.34 8.68 eosinophils BM unstim 39.56 3.6 3.60 BM unstim BM stim 40 1.34 1.34 BM stim -2.69 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 36.64 16.79 41.98 chondrocytes OA Synovium IP12/01 29462 34.75 45.45 45.45 OA Synovium OA Synovium NP10/01 29461 36.02 23.28 46.56 OA Synovium OA Synovium NP57/00 28464 34.24 59.37 118.74 OA Synovium RA Synovium NP03/01 28466 37.88 8.71 17.42 RA Synovium RA Synovium NP71/00 28467 36.02 23.22 46.44 RA Synovium RA Synovium NP45/00 28475 34.9 41.9 83.80 RA Synovium OA bone (biobank) 29217 33.59 83.75 83.75 OA bone (biobank) OA bone Sample 1 J. Emory 37.31 11.8 23.60 OA bone OA bone Sample 2 J. Emory 37.47 10.81 21.62 OA bone Cartilage (pool) Normal 34.61 49.07 .98.14 Cartilage (pool) Cartilage (pool) OA 40 0 0.00 Cartilage (pool) -98.14 PBL unifected 28441 33.86 72.8 145.60 PBL unifected PBL HIV IIIB 28442 37.08 13.28 26.56 PBL HIV IIIB -5.48 uninfected 29158 39.01 4.81 9.62 MRC5 uninfected (100%) (100%) HSV strain F 29178 31.5 252.68 505.36 MRC5 HSV strain 52.53

F

W12 cells 29179 39.84 3.1 6.20 W12 cells Keratinocytes 29180 39.07 4.64 9.28 Keratinocytes B-actin control 27.9 1683.49 genomic 28.13 1492.71 1.00E+05 20.5 100000 1.00E+05 20.61 100000 1.OOE+04 24.56 10000 1.00E+04 24.17 10000_ 1.00E+03 28.14 1000 1.00E+03 28.32 1000 1.00E+02 34.26 100 1.00E+02 32.76 100 1.00E+01 38.07 1.00E+01 37.53 1.00E-00 40 0 1.00E-00 40 1 NTC 38.42 -1 Gene Name sbg934114Relaxin Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -1.22 colon tumor -3.46 colon tumor -8.66 colon tumor -1.02 lung tumor -9.05 lung tumor 1.61 lung tumor -5.01 lung tumor 1.86 breast tumor -3.85 breast tumor 1.59 breast tumor 2.18 breast tumor 1.30 brain stage 5 ALZ 1.81 brain stage 5 ALZ 4.33 brain stage 5 ALZ 3.51 brain stage 5 ALZ 2.55 lung 24 -7.81 lung 28 -21.71 lung 23 -4.65 asthmatic lung 1.07 asthmatic lung 5.84 asthmatic lung 6.27 asthmatic lung 7.01 endo VEGF 0.00 endo bFGF 7.54 heart T-1 2.72 heart T-14 40.02 heart T-3399 25.40 BM stim -2.69 osteo dif 0.00 Cartilage (pool) -98.14 PBL HIV IB -5.48 HSV strain F 52.53 Gene Name sbg99174LOX-like Moderate overall expression in normal and disease samples. Highest normal expression in whole brain, liver, skin, spleen, testis. Shows relatively good expression in the female reproductive samples as well as the GI tract samples. Highest disease expression in one of the normal lung samples, one of the asthmatic lung samples, neutrophils, eosinophils, 2 of the RA synovium samples, and one of the OA bone samples. Downregulation in 1 of 4 lung tumor samples suggests possible implication in lung cancer. Upregulation in 2 of 4 breast tumors implies an involvement in cancers of the breast Downregulation in 1 of 4 AD brains along with the high expression seen in the brain suggests an involvement in Alzheimer's disease. Downregulation in 2 of 3 COPD lung samples implies an involvement in chronic obstructive pulmonary disease. Upregulation in 1 of 4 asthmatic lung samples implies a role in asthma. Downregulation in OA cartilage and high expression in OA and RA synovium suggests possible involvement in osteoarthritis and rheumatoid arthritis. Corroborating high expression in the T cells provides additional evidence for a role in RA/OA. Moderate expression in other immune cells.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg99174LOX-like 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 39.67, 34.48 0.53 11.91 6.22 3.06 16.34 101.63 Adipocytes Zenbio Subcutaneous Adipose 40, 39.75 0.39 0.51 0.45 0.96 52.36 23.56 Zenbio Adrenal Gland 38.61, 37.69 1 1.75 1.38 0.61 81.97 112.70 Clontech Whole Brain Clontech 30.59, 31.07 122.95 92.57 107.76 7.24 6.91 744.20 Fetal Brain Clontech 40, 40 0 0.29 0.15 0.48 103.95 15.07 Cerebellum Clontech 40, 40 0.4 0.4 0.40 2.17 23.04 9.22 Cervix 35.77, 40 5.52 0.62 3.07 2.42 20.66 63.43 Colon 40, 39.41 0.34 0.62 0.48 2.71 18.45 8.86 Endometrium 40, 38.65 0 0.98 0.49 0.73 68.21 33.42 Esophagus 40, 40 0.35 0.41 0.38 1.37 36.50 13.87 Heart Clontech 39.33,40 0.65 0 0.33 1.32 37.88 12.31 Hypothalamus 40, 39.54 0 0.58 0.29 0.32 155.28 45.03 Ileum 35.42, 35.76 6.79 5.55 6.17 2.58 19.38 119.57 Jejunum 34.13, 33.4 14.77 22.9 18.84 6.60 7.58 142.69 Kidney 40,37.22 0.68 2.32 1.50 2.12 23.58 35.38 Liver 33.5, 33.86 21.47 17.3 19.39 1.50 33.33 646.17 Fetal Liver Clontech 32.78, 33.23 33.08 25.33 29.21 10.40 4.81 140.41 Lung 33.96, 34.44 16.33 12.25 14.29 2.57 19.46 278.02 Mammary Gland 35.05, 36.02 8.51 4.76 6.64 13.00 3.85 25.52 Clontech Myometrium 35.08, 35.49 8.34 6.52 7.43 2.34 21.37 158.76 Omentum 37.6,35.05 1.83 8.49 5.16 3.94 12.69 65.48 Ovary 35.57, 32.76 6.21 33.46 19.84 4.34 11.52 228.51 Pancreas 40,40 0 0.42 0.21 0.81 61.80 12.98 Head of Pancreas 40,38.65 0.56 0.98 0.77 1.57 31.85 24.52 Parotid Gland 35.28,40 7.4 0.64 4.02 5.48 9.12 36.68 Placenta Clontech 40,39.17 0.32 0.72 0.52 5.26 9.51 4.94 Prostate 40, 35.34 0 7.15 3.58 3.00 16.67 59.58 Rectum 37.29, 39.02 2.22 0.78 1.50 1.23 40.65 60.98 Salivary Gland 40,38.15 0.27 1.32 0.80 7.31 6.84 5.44 Clontech Skeletal Muscle 40,38.56 0.56 1.03 0.80 1.26 39.68 31.55 Skin 35.1,34.19 8.22 14.22 11.22 1.21 41.32 463.64 Small Intestine 40,40 0 0.85 0.43 0.98 51.07 21.71 Spleen 32.2, 32.08 46.76 50.49 48.63 4.92 10.16 494.16 Stomach 34.28, 34.07 13.5 15.3 14.40 2.73 18.32 263.74 Testis Clontech 34.05,32.7 15.46 34.82 25.14 0.57 87.87 2209.14 Thymus Clontech 33.85,32.4 17.44 41.71 29.58 9.89 5.06 149.52 Thyroid 34.22,34.29 13.93 13.37 13.65 2.77 18.05 246.39 Trachea Clontech 32.51, 32.4 38.89 41.53 40.21 9.71 5.15 207.05 Urinary Bladder 35.47,40 6.6 0 3.30 5.47 9.14 30.16 Uterus 33.8,33.6 18.01 20.22 19.12 5.34 9.36 178.98 genomic 26.31 1603.29 b-actin 27.35 860.96 1.00E+05 19.71 100000 1.00E+05 19.88 100000 1.00E+04 22.98 10000 1.00E+04 23.01 10000 1.00E+03 26.44 1000 1.00E+03 26.54 1.00E+02 31.28 1.00E+02 31.29 1.00E+01 35.79 1.00E+01 34.36 1.00E-00 38.32 1.00E-00 40 1 NTC 40 0 NTC 40 Sample Reg Ct Mean copies Sample Fold sbg99174LOX-like number GOI Iof I IChange (GSK copies mRNA in identifier detecte Disease ug Populati total on colon normal GW98-167 21941 29.81 184.31 368.62 colon normal colon tumor GW98-166 21940 29.25 254.48 508.96 colon tumor 1.38 colon normal GW98-178 22080 32.06 50.31 100.62 colon normal colon tumor GW98-177 22060 31.77 59.28 118.56 colon tumor 1.18 colon normal GW98-561 23514 33.21 125.83 51.66 colon normal colon tumor GiW98-560 23513 31.74 60.51 1121.02 colon tumor 2.34 colon normal GW98-894 24691 30.17 149.84 299.68 colon normal colon tumor GW98-893 24690 29.41 232.23 464.46 colon tumor 1.55 lung normal GW98-3 20742 25.76 1914.72 3829.44 lung normal lung tumor GW98-2 20741 30.12 154.63 309.26 lung tumor -12.38 lung normal GW97- 179 20677 29.59 1209.5 419.00 lung normal lung tumor GW97-178 20676 27.2 1835.04 1670.08 lung tumor 3.99 lung normal GW98-165 21922 28.22 462.22 924.44 lung normal lung tumor GW98-164 21921 29.27 251.87 503.74 lung tumor -1.84 lung normal GW98-282 22584 30.18 149.17 1298.34 lung normal lung tumor GW98-281 22583 28.47 399.41 798.82 lung tumor 2.68 breast normal GWOO-392 28750 30.24 143.58 143.58 breast normal breast tumor GWOO-391 28746 30.16 151.08 302.16 breast tumor 2.10 breast normal GWOO-413 28798 31.51 168.87 68.87 breast normal breast tumor GWOO-412 28797 28.91 310.66 1621.32 breast tumor 9.02 breast normal GW00- 27592-95 40 0 0.00 breast normal 235:238 breast tumor GWOO- 27588-91 33.55 21.28 21.28 breast tumor 21.28 231:234 breast normal GW98-621 23656 31.57 66.56 133.12 breast normal breast tumor GW98-620 23655 31.15 84.8 169.60 breast tumor 1.27 brain normal BB99-542 25507 29.55 214.38 1428.76 brain normal brain normal BB99-406 25509 29.15 270.89 541.78 brain normal brain normal BB99-904 25546 30.48 124.98 249.96 brain normal brain stage 5 ALZ BB99- 25502 33.57 20.99 41.98 brain stage 5 ALZ -9.69 874 brain stage 5 ALZ BB99- 25503 29.89 176.42 352.84 brain stage 5 ALZ -1.15 887 brain stage 5 ALZ BB99- 25504 31.65 63.83 127.66 brain stage 5 ALZ -3.19 862 brain stage 5 AIZ 13199- 25542 31.04 90.73 181.46 brain stage 5 AUZ -2.24 927 1__ Cr lung KC normal 29.94 1170.8 341.60 CT lung lung 26 KC normal 30.63 115.04 115.04 lung 26 lung 27 KC normal 32.22 45.83 45.83 lung 27 lung 24 KC COPD 34.16 14.91 14.91 lung 24 -9.21 lung 28KC COPD 33.51 21.7 21.70 lung 28 -6.33 lung 23 KC COPD 32.51 138.67 138.67 lung 23 -3.55 lung 25 KG normal 32.18 146.79 146.79 lung 25 asthmatic lung 0D03112129321 31.84 156.95 156.95 1asthmatic lung 1-2.41 asthmatic lung OD03433 29323 31.12 86.42 172.84 asthmatic lung 1.26 asthmatic lung OD03397 29322 27.13 867.31 1734.62 asthmatic lung 12.63 asthmatic lung OD04928 29325 30.25 142.92 285.84 asthmatic lung 2.08 endo cells KC control 31.23 81.05 81.05 endo cells endo VEGF KC 131.87 56.15 56.15 endo VEGF -1.44 endo bFGF KC 32.64 35.97 35.97 endo bFGF -2.25 heart Clontech normal 35.46 7.06 14.12 heart heart T-1) ischemic 29417 35.73 6.03 12.06 heart T-1 -1.17 heart (T-14) non- 29422 34.34 13.49 26.98 heartT-14 1.91 obstructive DCM heart (T-3399) DCM 29426 33.65 20.01 40.02 heart T-3399 2.83 adenoid GW99-269 26162 31.2 82.69 165.38 adenoid tonsil GW98-280 22582 30.8 103.96 207.92 tonsil T cells PC00314 28453 28.16 480.4 960.80 T cells PBMNC 30.25 143.11 143.11 PBMNC monocyte 30.05 160.68 321.36 monocyte B cells PC00665 28455 30.75 107.02 214.04 B cells dendritic cells 28441 30.32 137.17 274.34 dendritic cells neutrophils 28440 26.32 1390.87 1390.87 neutrophils eosinophils 28446 25.07 2854.44 5708.88 eosinophils BM unstim 30.72 109.05 109.05 BM unstim BM stim 28.61 369.2 369.20 BM stim 3.39 osteo dif 40 0 0.00 osteo dif -0.28 osteo undif 40 0.28 0.28 osteo undif chondrocytes 34.3 13.76 34.40 chondrocytes OA Synovium IP12/01 29462 27.56 676.63 676.63 OA Synovium OA Synovium NPl0/01 29461 31.41 73.19 146.38 OA Synovium OA Synovium NP57/00 28464 28.02 518.05 1036.10 OA Synovium RA Synovium NPO3/01 28466 27.03 921.88 1843.76 RA Synovium RA Synovium NP71/00 28467 27.04 914.02 1828.04 RA Synovium RA Synovium NP45/00 28475 29.06 285.08 570.16 RA Synovium OA bone (biobank) 29217 26.78 1065.84 1065.84 OA bone SI (biobank) OA bone Sample 1 J. Emory 30.27 141.07 282.14 OA bone OA bone Sample 2 J. Emory 27.04 917.04 1834.08 OA bone Cartilage (pool) Normal 28.23 461.21 922.42 Cartilage (pool) Cartilage (pool) OA 33.16 26.65 53.30 Cartilage (pool) -17.31 PBL unifected 28441 28.72 346.97 693.94 PBL unifected PBL HIV IIIB 28442 28.54 384.02 768.04 PBL HIV IIIB 1.11 uninfected 29158 31.64 64.07 128.14 MRC5 uninfected 10 0 HSV strain F 29178 31.53 68.31 136.62 MRC5 HSV strain 1.07

F

W12 cells 29179 34.44 12.72 25.44 W12 cells Keratinocytes 29180 36.02 5.1 10.20 Keratinocytes B-actin control 27.2 835.98 genomic 26.76 1073.72 1.00E+05 19.13 100000 1.00E+05 19.61 100000 L.OOE+04 22.79 10000 1.OOE-i04 22.5 10000 1.OOE+03 26.36 1000 1.OOE+03 26.23 1000 1.00E±02 31.25 1100 1.00E+02 30.82 1100 1.00E+01 35.02 35.15 1.OOE-00 40 0 1.OO13-00 140 0 NTC 140 Gene Name sbg99l74LOX-Iike Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.38 colon tumor 1.18 colon tumor 2.34 colon tumor 1.55 lung tumor -12.38 lung tumor 3.99 lung tumor -1.84 lung tumor 2.68 breast tumor 2.10 breast tumor 9.02 breast tumor 21.29 breast tumor 1.27 brain stage 5 ALZ -9.69 brain stage 5 ALZ -1.15 brain stage 5 ALZ -3.19 brain stage 5 ALZ -2.24 lung 24 -9.21 lung_28 -6.33 lung 23 -3.55 asthmatic lung -2.41 asthmatic lung 1.26 asthmatic lung 12.63 asthmatic lung 2.08 endo VEGF -1.44 endo bFGF -2.25 heart T- 1 -1.17 heart T-14 1.91 heart T-3399 2.83 BM stim 3.39 osteo dif -0.28 Cartilage (pool) -17.31 PBLHMVIIEM 1.11 HSV strain F 1.07 Gene Name sbg995002PIGR (Taqman) Extremely low overall expression in normal and disease samples. Highest normal expression in the colon and the parotid gland. Highest disease expression in the one of the lung tumors and one of the colon tumors. Upregulation in 1 of 4 colon tumors and 1 of 4 lung tumors imply roles in cancers of the colon and lung. Downregulation in 3 of 4 AD brain samples as well as high expression in whole brain suggests an involvement in Alzheimer's disease. Downregulation in 3 of 3 COPD lung samples implicates this gene in COPD. Downregulation in the ischemic and nonobstructive DCM heart samples suggests a role for this gene in cardiovascular disease.

Upregulation in the stimulated bone marrow sample. Upregulation in HSV implicates involvement in herpes simplex virus as a potential host factor. High expression in neutrophils and eosinophils.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg995002PIGR I and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 40,40 0 0 0.00 3.06 16.34 0.00 Adipocytes Zenbio Subcutaneous Adipose 40,40 0 0 0.00 0.96 52.36 0.00 Zenbio Adrenal Gland Clontech 40,40 0 0 0.00 0.61 81.97 0.00 Whole Brain Clontech 36.78,40 11.16 0 5.58 7.24 6.91 38.54 Fetal Brain Clontech 40,40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 40,40 0 0 0.00 2.17 23.04 0.00 Cervix 40,40 0 0 0.00 2.42 20.66 0.00 Colon 37.16, 37.12 8.81 9.05 8.93 2.71 1 8.45 164.76 Endometrium 40,40 0 0 0.00 0.73 68.21 0.00 Esophagus 40,40 0 0 0.00 1.37 36.50 0.00 Heart Clontech 40,40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40,40 0 0 0.00 0.32 155.28 0.00 Ileum 40,40 0 0 0.00 2.58 19.38 0.00 Jejunum 40,40 0 0 0.00 6.60 7.58 0.00 Kidney 40,40 0 0 0.00 2.12 23.58 0.00 40, 39.16 0 2.58 1.29 1.50 33.33 43.00 Fetal Liver Clontech 40,40 0 0 0.00 10.40 4.81 0.00 Lung 40,40 0 0 0.00 2.57 19.46 0.00 Mammary Gland 40,39.18 0 2.55 1.28 13.00 3.85 4.90 Clontech Myometrium 40,40 0 0 0.00 2.34 21.37 0.00 Omentum 40,38.04 0 5.15 2.58 3.94 12.69 32.68 Ovary 39.29,40 2.37 0 1.19 4.34 11.52 13.65 Pancreas 40,40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40,40 0 0 0.00 1.57 31.85 000 Parotid Gland 36.7, 37.94 11.72 5.46 8.59 5.48 9.12 78.38 Placenta Clontech 40,40 0 0 0.00 5.26 9.51 0.00 Prostate 40,40 0 0 0.00 3.00 16.67 0.00 Rectum 40,40 0 0 0.00 1.23 40.65 0.00 Salivary Gland 37.23, 39.21 8.45 2.5 5.48 7.31 6.84 37.45 Clontech Skeletal Muscle 40,40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 40,40 0 0 0.00 1.21 41.32 0.00 Small Intestine 40,40 0 0 0.00 0.98 51.07 0.00 Clontech Spleen 40, 38.76 1.25 3.3 2.28 4.92 10.16 23.12 Stomach 40, 39.25 1.25 2.43 1.84 2.73 18.32 33.70 Testis Clontech 40, 40 0 0 0.00 0.57 87.87 0.00 Thymus Clontech 37.82,40 5.88 0 2.94 9.89 5.06 14.86 Thyroid 40, 40 0 0 0.00 2.77 18.05 0.00 Trachea Clontech 40,40 0 0 0.00 9.71 5.15 0.00 Urinary Bladder 40, 40 0 0 0.00 5.47 9.14 0.00 Uterus 38.34,40 4.27 0 2.14 5.34 9.36 19.99 genomic 29.66 888.99 b-actin 30.72 462.87 1.OOE+05 22.2 100000 1.OOE+05 22.14 100000 1.00E+04 25.72 10000 1.00E+04 25.66 10000 1.OOE+03 29.16 1000 1.00E+03 29.07 1000 1.00E+02 32.37 100 1.OOE+02 34.12 100 L.OOE+01 37.12 1.00E+01 37.11 1.00E-00 40 0 LO0E-00 40 0 NTC 40 0 NTC 38.03 -1 Sample Reg Ct Mean copies Sample Fold sbg995002PIGR number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populati total on

RNA

colon normal GW98-167 21941 33.43 149.84 299.68 colon normal colon tumor GW98-166 21940 32.49 274.64 549.28 colon tumor 1.83 colon normal GW98-178 22080 40 0 0.00 colon normal colon tumor GW98-177 22060 31.11 675.8 1351.60 colon tumor 1351.60 colon normal GW98-561 23514 37.74 9.09 18.18 colon normal colon tumor GW98-560 23513 35.81 31.94 63.88 colon tumor 3.51 colon normal GW98-894 24691 33.17 177.11 354.22 colon normal colon tumor GW98-893 24690 31.61 488.49 976.98 colon tumor 2.76 lung normal GW98-3 20742 35.48 39.55 79.10 lung normal lung tumor GW98-2 20741 28.32 4121.56 8243.12 lung tumor 104.21 lung normal GW97-179 20677 36.47 20.69 41.38 lung normal lung tumor GW97-178 20676 37.24 12.59 25.18 lung tumor -1.64 lung normal GW98-165 21922 37.32 11.96 23.92 lung normal lung tumor GW98-164 21921 36.07 26.9 53.80 lung tumor 2.25

IND

0 kn

IN

lung normal GW98-282 22584 38.49 5.58 11.16 lung normal lung tumor GW98-281 22583 37.89 8.24 16.48 lung tumor 1.48 breast normal GWOO-392 28750 39.03 3.93 3.93 breast normal breast tumor GWOO-391 28746 38.01 7.65 15.30 breast tumor 3.89 breast normal GW0O-413 28798 40 0 0.00 breast normal breast tumor GWOO-412 28797 38.67 4.98 9.96 breast tumor 9.96 breast normal GWOO- 27592-95 40 0 0.00 breast normal 235:238 breast tumor GWOO- 27588-91 40 0 0.00 breast tumor 0.00 231:234 breast normal GW98-621 23656 36.12 26.13 52.26 breast normal breast tumor GW98-620 23655 40 0 0.00 breast tumor -52.26 brain normal BB99-542 25507 37.14 13.43 26.86 brain normal brain normal BB99-406 25509 40 0 0.00 brain normal brain normal BB99-904 25546 40 0 0.00 brain normal brain stage 5 ALZ BB99- 25502 40 0 0.00 brain stage 5 ALZ -8.95 874 brain stage 5 ALZ BB99- 25503 40 0.51 1.02 brain stage 5 ALZ -8.78 887 brain stage 5 ALZ BB99- 25504 40 0.88 1.76 brain stage 5 ALZ -5.09 862 brain stage 5 ALZ BB99- 25542 40 1.9 3.80 brain stage 5 ALZ -2.36 927 CT lung KC normal 36.59 19.23 38.46 CT lung lung 26 KC normal 40 0 0.00 lung 26 lung 27 KC normal 40 0 0.00 lung 27 lung 24 KC COPD 40 0 0.00 lung 24 -9.62 lung 28 KC COPD 40 0 0.00 lung 28 -9.62 lung 23 KC COPD 40 0 0.00 lung 23 -9.62 lung 25 KC normal 40 0 0.00 lung asthmatic lung OD03112 29321 40 0 0.00 asthmatic lung -9.62 asthmatic lung OD03433 29323 38.36 6.1 12.20 asthmatic lung 1.27 asthmatic lung OD03397 29322 37.29 12.16 24.32 asthmatic lung 2.53 asthmatic lung OD04928 29325 38.01 7.64 15.28 asthmatic lung 1.59 endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 40 0 0.00 endo bFGF 0.00 heart Clontech normal 37.85 8.49 16.98 heart heart T-1 ischemic 29417 40 0 0.00 heart T-1 -16.98 heart (T-14) non- 29422 40 0 0.00 heart T-14 -16.98 obstructive DCM

I

heart (T-3399) DCM 29426 39.5 2.9 5.80 heart T-3399 -2.93 adenoid GW99-269 26162 40 0 0.00 adenoid tonsil GW98-280 22582 36.35 22.46 44.92 tonsil T cells PC00314 28453 36.17 25.23 50.46 T cells PBMNC 40 0 0.00 PBMNC monocyte 40 0.45 0.90 monocyte B cells PC00665 28455 40 0.6 1.20 B cells dendritic cells 28441 38.07 7.37 14.74 dendritic cells neutrophils 128440 132.73 236.09 236.09 neutrophils eosinophils 28446 33.68 126.65 253.30 eosinophils BM unstim 40 0 0.00 BM unstim BM stim 36.52 20.1 20.10 BM stim 20.10 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 39.61 2.7 6.75 chondrocytes OA Synovium 1P12/01 29462 39.91 1.59 1.59 OA Synovium OA Synovium NP1O/01 29461 38.98 4.07 8.14 OA Synovium OA Synovium NP57/00 28464 36.29 23.27 46.54 OA Synovium RA Synovium NP03/01 28466 35.81 31.94 63.88 RA Synovium RA Synovium NP71/00 28467 34.79 61.79 123.58 RA Synovium RA Synovium NP45/00 28475 35.08 51.15 102.30 RA Synovium OA bone (biobank) 29217 40 1.12 1.12 OA bone OA bone Sample I J. Emory 36.8 16.77 33.54 OA bone OA bone Sample 2 J. Emory 34.72 64.74 129.48 OA bone Cartilage (pool) Normal 37.46 10.93 21.86 Cartilage (pool) Cartilage (pool) OA 40 0 0.00 Cartilage (pool) -21.86 PBL unifected 28441 35.05 52.27 104.54 PBL unifected PBL HV IMIIB 28442 37.31 12.04 24.08 PBL HIV DIE -4.34 uninfected 29158 40 0 0.00 MRC5 uninfected (100%) 100%) MRCS HSV strain F 29178 38.19 6.8 13.60 MRCS HSV strain 13.60 W12 cells 29179 40 0 0.00 W12 cells Keratinocytes 29180 40 0 0.00 Keratinocytes B-actin control B-actin 29.77 1604.25 control genomic genomic 30.5 1001.61 1.OOE+05 1.00E+05 22.95 100000 1.00E+05 1.OOE+05 22.91 100000 1.OOE+04 1.OOE+04 26.49 10000 1.00E+04 1.00E+04 26.66 10000 1.00E+03 1.00E+03 30.62 1000 1.OOE+03 1.00E+03 30.43 1000 1.OOE+02 1.00E+02 36.12 100 1.00E+02 1.00E+02 34.73 100 l.00E+01 1.00E+01 38.58 l.00E+01 1.OOE+01 38.82 1.OOE-00 I.00E-00 40 0 1.OOE-00 1.00E-00 37.86 1 NTC NTC 40 0 1 Gene Name sbg995002PIGR Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.83 colon tumor 1351.60 colon tumor colon tumor 2.76 lung tumor 104.21 lung tumor -1.64 lung tumor 2.25 lung tumor 1.48 breast tumor 3.89 breast tumor 9.96 breast tumor 0.00 breast tumor -52.26 brain stage 5 ALZ -8.95 brain stage 5 ALZ -8.78 brain stage 5 ALZ -5.09 brain stage 5 ALZ -2.36 lung 24 -9.62 lung -9.62 lung 23 -9.62 asthmatic lung -9.62 asthmatic lung 1.27 asthmatic lung 2.53 asthmatic lung 1.59 endo VEGF 0.00 endo bFGF 0.00 heart T- 1 -16.98 heart T-14 -16.98 heart T-3399 -2.93 BM stim 20.10 osteo dif 0.00 Cartilage (pool) -21.86 PBLHIV IIIB -4.34 HSV strain F 13.60 Gene Name sbg1033026Clq Low to moderate overall expression in normal and disease samples. Highest normal expression in the subcutaneous adipocytes, subcutaneous adipose, whole brain, and heart. Highest disease expression in the 3 heart samples. Downregulation in I of 4 lung tumor samples and upregulation in 2 of 4 breast tumor samples indicates a role for this gene in cancers of the lung and breast Upregulation in 2 of 4 AD brain samples suggests an involvement in Alzheimer's disease.

Upregulation in 3 of 3 heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM as well as ischemia. Low expression in all of the immune cells. Low to moderate expression in the OA synovium and bone samples as well as in the RA synovium samples.

Sample Ct (sample Mean Mean Average 18S 50 copies sbgl033026Clq 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total Subcutaneous 32.32,31.18 11.99 24.91 18.45 3.06 16.34 301.47 Adipocytes Zenbio Subcutaneous Adipose 34.95, 33.78 2.2 4.69 3.45 0.96 52.36 180.37 Zenbio Adrenal Gland 40, 40 0 0 0.00 0.61 81.97 0.00 Clontech Whole Brain Clontech 28.5, 28.04 140.11 187.98 164.05 7.24 6.91 1132.91 Fetal Brain Clontech 40, 40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 40, 40 0 0 0.00 2.17 23.04 0.00 Cervix 40, 40 0 0 0.00 2.42 20.66 0.00 Colon 34.82, 38.44 2.39 0.23 1.31 2.71 18.45 24.17 Endometriurn 40, 35.09 0 2.01 1.01 0.73 68.21 68.55 Esophagus 40, 40 0 0 0.00 1.37 36.50 0.00 Heart Clontech 32.53, 34.31 10.45 3.32 6.89 1.32 37.88 260.80 Hypothalamus 40,40 0 0 0.00 0.32 155.28 0.00 Ileum 40, 34.55 0 2.85 1.43 2.58 19.38 27.62 Jejunum 33.04, 34.86 7.51 2.33 4.92 6.60 7.58 37.27 Kidney 40,40 0 0 0.00 2.12 23.58 0.00 Liver 35.81, 33.92 1.26 4.28 2.77 1.50 33.33 92.33 Fetal Liver Clontech 32.05,40 14.25 0 7.13 10.40 4.81 34.25 Lung 40, 33.51 0 5.58 2.79 2.57 19.46 54.28 Mammary Gland 31.05, 30.69 27.02 34.2 30.61 13.00 3.85 117.73 Clontech Myometrium 33.29, 35.1 6.42 2 4.21 2.34 21.37 89.96 Omentum 34.44,40 3.07 0 1.54 3.94 12.69 19.48 Ovary 32.59, 35.04 10.03 2.07 6.05 4.34 11.52 69.70 Pancreas 40, 40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40,40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 34.63,33.09 2.71 7.29 5.00 5.48 9.12 45.62 Placenta Clontech 32.77, 33.01 8.94 7.7 8.32 5.26 9.51 79.09 Prostate 40, 40 0 0 0.00 3.00 16.67 0.00 Rectum 40, 34.44 0 3.06 1.53 1.23 40.65 62.20 Salivary Gland 32.96, 40 7.94 0 3.97 7.31 6.84 27.15 Clontech I Skeletal Muscle 40, 40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 40, 33.46 0.6 5.75 3.18 1.21 41.32 131.20 Small Intestine 40, 40 0 0 0.00 0.98 51.07 0.00 Clontech Spleen 35.65, 35 1.4 2.13 1.77 4.92 10.16 17.94 Stomach 40, 34.73 0 2.54 1.27 2.73 18.32 23.26 Testis Clontech 40, 35.12 0 1.98 0.99 0.57 87.87 86.99 Thymus Clontech 32.44,31.57 11.11 19.37 15.24 9.89 5.06 77.05 Thyroid 40, 40 0 0 0.00 2.77 18.05 0.00 Trachea Clontech 34.58, 33.56 2.79 5.4 4.10 9.71 5.15 21.09 Urinary Bladder 33.45, 33.34 5.8 6.21 6.01 5.47 9.14 54.89 Uterus 33.19, 32.41 6.82 11.32 9.07 5.34 9.36 84.93 genomic 25.47 981.57 b-actin 26.87 398.61 1.OOE+05 18.24 100000 1.00E+05 18.35 100000 1.00E+04 21.53 10000 1.OOE+04 21.62 10000 1 1.OOE+03 25.17 1000 1.00E+03 25.03 1000 1.OOE+02 30.53 100 1.00E+02 30.49 100 !.OOE+01 30.85 1.OOE+01 40 1.OOE-00 40 0 1.00E-00 40 0 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies Sample Fold sbg1O33026Clq number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populat total ion

RNA

colon normal GW98-167 21941 27.03 397.15 794.30 colon normal colon tumor GW98-166 21940 29.53 91.39 182.78 colon tumor -4.35 colon normal GW98-178 22080 30.3 57.81 115.62 colon normal colon tumor GW98-177 22060 29.31 103.84 207.68 colon tumor 1.80 colon normal GW98-561 23514 28.79 140.64 281.28 colon normal colon tumor GW98-560 23513 30.18 62.18 124.36 colon tumor -2.26 colon normal GW98-894 24691 28.31 187.28 374.56 colon normal colon tumor GW98-893 24690 28.75 143.93 287.86 colon tumor -1.30 lung normal GW98-3 20742 28.18 201.78 403.56 lung normal lung tumor GW98-2 20741 32.35 17.41 34.82 lung tumor -11.59 lung normal GW97-179 20677 29.94 71.52 143.04 lung normal lung tumor GW97-178 20676 28.76 143.36 286.72 lung tumor 2.00 lung normal GW98-165 21922 28.69 149.49 298.98 lung normal lung tumor GW98-164 21921 31.28 32.63 65.26 lung tumor -4.58 lung normal GW98-282 22584 31.42 30.07 60.14 lung normal lung tumor GW98-281 22583 30.33 56.83 113.66 lung tumor 1.89 breast normal GWOO-392 28750 28.72 146.7 146.70 breast normal breast tumor GWOO-391 28746 27.02 398.56 797.12 breast tumor 5.43 breast normal GWOO-413 28798 30.95 39.63 39.63 breast normal breast tumor GWOO-412 28797 30.58 49.03 98.06 breast tumor 2.47 breast normal GWOO- 27592-95 32.53 15.6 15.60 breast normal 235:238 breast tumor GWOO- 27588-91 29.58 88.49 88.49 breast tumor 5.67 231:234 breast normal GW98-621 23656 27.5 300.39 600.78 breast normal breast tumor GW98-620 23655 29.28 105.43 210.86 breast tumor -2.85 brain normal BB99-542 25507 30.67 46.59 93.18 brain normal L brain normal BB99-406 25509 29.54 90.66 181.32 brain normal brain normal BB99-904 25546 31.13 35.58 71.16 brain normal brain stage 5 ALZ BB99- 25502 31.4 30.36 60.72 brain stage 5 ALZ -1.90 874 1_1_1 brain stage 5 ALZ BB99- 25503 28.39 177.94 355.88 brain stage 5 ALZ 3.09 887 brain stage 5 ALZ BB99- 25504 28.92 130.19 260.38 brain stage 5 ALZ 2.26 862 brain stage 5 ALZ BB99- 25542 28.2 198.98 397.96 brain stage 5 ALZ 3.45 927 CT lung KC normal 31.24 33.37 66.74 CT lung lung 26 KC normal 33.59 8.37 8.37 lung 26 lung 27 KC normal 37.8 0.7 0.70 lung 27 lung 24 KC COPD 34.56 4.73 4.73 lung 24 -4.39 lung 28 KC COPD 35.39 2.91 2.91 lung 28 -7.13 lung 23 KC COPD 34.74 4.26 4.26 lung 23 -4.87 lung 25 KC normal 33.85 7.19 7.19 lung asthmatic lung OD03112 29321 35.04 3.57 3.57 asthmatic lung -5.81 asthmatic lung OD03433 29323 32.44 16.48 32.96 asthmatic lung 1.59 asthmatic lung OD03397 29322 29.4 98.44 196.88 asthmatic lung 9.49 asthmatic lung OD04928 29325 31.1 36.23 72.46 asthmatic lung 3.49 endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 35.4 2.89 2.89 endo bFGF 2.89 heart Clontech normal 29.05 120.78 241.56 heart heart T-1 ischemic 29417 26.23 633.79 1267.58 heart T-1 5.25 heart (T-14) non- 29422 25.74 847.85 1695.70 heart T-14 7.02 obstructive DCM_ heart (T-3399) DCM 29426 25.03 1289.37 2578.74 heart T-3399 10.68 adenoid GW99-269 26162 35.24 3.17 6.34 adenoid tonsil GW98-280 22582 31 38.35 76.70 tonsil T cells PC00314 28453 31.75 24.69 49.38 T cells PBMNC 40 0 0.00 PBMNC monocyte 40 0 0.00 monocyte B cells PC00665 28455 31.35 31.31 62.62 B cells dendritic cells 28441 32.81 13.25 26.50 dendritic cells neutrophils 28440 31.76 24.51 24.51 neutrophils eosinophils 28446 33.08 11.29 22.58 eosinophils BM unstim 36.9 1.19 1.19 BM unstim BM stim 38.86 0.38 0.38 BM stim -3.13 osteo dif 37.77 0.72 0.72 osteo dif 0.72 osteo undif 40 0 0.00 osteo undif chondrocytes 33.14 10.88 27.20 chondrocytes OA Synovium IP12/01 29462 30.61 48.28 48.28 OA Synovium OA Synovium NP10/01 29461 27.5 300.97 601.94 OA Synovium OA Synovium NP57/00 28464 29.28 105.55 211.10 OA Synovium RA Synovium NP03/01 28466 30.18 62.3 124.60 RA Synovium RA Synovium NP71/00 28467 29.22 109.5 219.00 RA Synovium RA Synovium NP45/00 28475 30.06 66.71 133.42 RA Synovium OA bone (biobank) 29217 32.6 14.99 14.99 OA bone (biobank) OA bone Sample 1 J. Emory 30.48 52.25 104.50 OA bone OA bone Sample 2 J. Emory 32.31 17.76 35.52 OA bone Cartilage (pool) Normal 30.45 53.05 106.10 Cartilage (pool) Cartilage (pool) OA 30.81 43.01 86.02 Cartilage (pool) -1.23 PBL unifected 28441 30.19 61.92 123.84 PBL unifected PBL HIV IIIB 28442 31.19 34.35 68.70 PBL HIV IIIB -1.80 uninfected 29158 30.19 62.02 124.04 MRC5 uninfected (100%) HSV strain F 29178 31.13 35.48 70.96 MRC5 HSV strain -1.75

F

W12 cells 29179 32 21.32 42.64 W12 cells Keratinocytes 29180 33.3 9.92 19.84 Keratinocytes B-actin control 26.66 492.23 genomic 24.83 1443.91 1.00E+05 18.12 100000 1.00E+05 18.12 100000 1.00E+04 21.28 10000 1.OOE+04 21.31 10000 1.00E+03 24.92 1000 1.OOE+03 24.9 1000 1.00E+02 29.22 100 1.00E+02 29.26 100 1.00E+01 33.13 1.00E+01 34.32 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 Gene Name sbgl033026Clq Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -4.35 colon tumor 1.80 colon tumor -2.26 colon tumor -1.30 lung tumor -11.59 lung tumor 2.00 lung tumor -4.58 lung tumor 1.89 breast tumor 5.43 breast tumor 2.47 breast tumor 5.67 breast tumor -2.85 brain stage 5 ALZ -1.90 brain stage 5 ALZ 3.09 brain stage 5 ALZ 2.26 brain stage 5 ALZ 3.45 lung 24 -4.39 lung 28 -7.13 lung 23 -4.87 asthmatic lung -5.81 asthmatic lung 1.59 asthmatic lung 9.49

I

asthmatic lung 3.49 endo VEGF 0.00 endo bFGF 2.89 heart T-1 5.25 heart T-14 7.02 heart T-3399 10.68 BM stim -3.13 osteo dif 0.72 Cartilage (pool) -1.23 PBL HIV IIIB -1.80 HSV strain F -1.75 Gene Name sbgl003675Rnase

FAILED

Gene Name sbg1015258PLM Low overall expression in normal and disease samples. Highest normal expression in the endometrium, hypothalamus, liver small intestine, and the testis. Highest disease expression in one of the breast normal/tumor pairs, one of the normal brain samples, two of the Alzheimer's disease brain samples, the B cells and the HSV-infected MRC5 cells. Downregulation in 1 of 4 lung tumor samples is sufficient to claim a role in cancer of the lung. Upregulation in 2 of 4 breast tumor samples indicates an involvement in cancer of the breast. Downregulation in 2 of 3 COPD samples and in 1 of 4 asthmatic lung samples implies a role in chronic obstructive pulmonary disease and asthma. Upregulation in the obstructive DCM heart sample suggests a potential role in cardiovascular disease. Downregulation in the stimulated bone marrow sample. Downregulation in the OA cartilage pool implicates this gene in osteoarthritis. Upregulation in the HSV-infected cells suggests that this gene may be a host factor in HSV. Low expression in all immune cells except the B cells which show moderate expression.

Sample Ct (sample Mean Mean Average 18S 50 copies of sbg1015258PLM 1 and 2) GOI GOI GOI rRNA ng/18S mRNA copies copies Copies (ng) rRNA detected/ (sample (sample (ng) 50 ng 1) 2) total

RNA

Subcutaneous 39.96, 39.32 0.39 0.73 0.56 3.06 16.34 9.15 Adipocytes Zenbio Subcutaneous Adipose 39.61, 37.77 0.62 1.84 1.23 0.96 52.36 64.40 Zenbio Adrenal Gland Clontech 36.89, 37.65 3.12 1.98 2.55 0.61 81.97 209.02 Whole Brain Clontech 32.77, 33.06 36.18 30.37 33.28 7.24 6.91 229.80 Fetal Brain Clontech 38.01, 37.52 1.6 2.14 1.87 0.48 103.95 194.39 Cerebellum Clontech 38.34, 37.8 1.31 1.81 1.56 2.17 23.04 35.94 Cervix 36.9, 37.17 3.1 2.64 2.87 2.42 20.66 59.30 Colon 35.93, 37.95 5.51 1.66 3.59 2.71 18.45 66.14 Endometrium 34.62, 37.51 12.02 2.15 7.09 0.73 68.21 483.29 Esophagus 35.76, 37.39 6.1 2.31 4.21 1.37 36.50 153.47 Heart Clontech 36.78, 38.53 3.33 1.17 2.25 1.32 37.88 85.23 Hypothalamus 37.12, 36.52 2.71 3.87 3.29 0.32 155.28 510.87 Ileum 36.15, 36.19 4.84 4.72 4.78 2.58 19.38 92.64 Jejunum 34.6, 33.48 12.14 23.65 17.90 6.60 7.58 135.57 Kidney 37.16, 37.9 2.65 1.7 2.18 2.12 23.58 51.30 Liver 34.6, 36.06 12.13 5.11 8.62 1.50 33.33 287.33 Fetal Liver Clontech 34.32, 36.91 14.35 3.07 8.71 10.40 4.81 41.88 Lung 36.94, 35.31 3.02 7.98 5.50 2.57 19.46 107.00 Mammary Gland 38.03, 36.89 1.58 3.11 2.35 13.00 3.85 9.02 Clontech Myometrium 38.44,38 1.24 1.6 1.42 2.34 21.37 30.34 Omentum 35.41,35.38 7.51 7.64 7.58 3.94 12.69 96.13 Omentum Ovary 34.32, 34.36 14.4 14.07 14.24 4.34 11.52 164.00 Pancreas 36.44, 36.82 4.07 3.25 3.66 0.81 61.80 226.21 Head of Pancreas 37.54, 36.96 2.11 2.98 2.55 1.57 31.85 81.05 Parotid Gland 37.1, 35.46 2.75 7.29 5.02 5.48 9.12 45.80 Placenta Clontech 36.07, 35.36 5.08 7.74 6.41 5.26 9.51 60.93 Prostate 37.4,37.82 2.3 1.79 2.05 3.00 16.67 34.08 Rectum 36.65, 37.39 3.59 2.32 2.96 1.23 40.65 120.12 Salivary Gland 38.55, 39.31 1.16 0.74 0.95 7.31 6.84 6.50 Clontech

I

Skeletal Muscle 37.59, 36.87 2.06 3.15 2.61 1.26 39.68 103.37 Clontech Skin 38.36, 36.33 1.3 4.34 2.82 1.21 41.32 116.53 Small Intestine 36.05, 36.76 5.14 3.37 4.26 0.98 51.07 217.31 Clontech Spleen 37.62,35.34 2.02 7.83 4.93 4.92 10.16 50.05 Stomach 35.8, 35.15 5.95 8.76 7.36 2.73 18.32 134.71 Testis Clontech 35.14, 37.08 8.82 2.77 5.80 0.57 87.87 509.23 Thymus Clontech 35.89, 35.06 5.65 9.22 7.44 9.89 5.06 37.59 Thyroid 37.59, 37.2 2.06 2.59 2.33 2.77 18.05 41.97 Trachea Clontech 37.52,37.95 2.14 1.66 1.90 9.71 5.15 9.78 Urinary Bladder 37.47, 35.44 2.2 7.38 4.79 5.47 9.14 43.78 Uterus 34.17,34.12 15.66 16.17 15.92 5.34 9.36 149.02 genomic 27.03 1097.52 b-actin 27.23 974.77 1.00E+05 19.25 100000 1.00E+05 19.2 100000 1.00E+04 22.99 10000 1.00E+04 22.94 10000 1.00E+03 27.09 1000 1.00E+03 27.28 1000 1.00E+02 31.49 100 1.00E+02 31.46 100 1.OOE+01 37.86 1.OOE+01 35.45 1.00E-00 37.08 1 1.OOE-00 37.4 1 NTC 36.45 -1 NTC 36.15 -1 Sample Reg Ct Mean copies of Sample Fold I sbglOlS258PLM In umberI GOI mRNA I I -Change in (GSK copies detected/ Disease identifier 50 ug Population total RNA colon normal GW98-167 21941 35.4 9.91 19.82 colon normal colon tumor GW98-166 21940 35.13 11.61 23.22 colon tumor 1.17 colon normal GW98-179 22080 34.84 13.83 27.66 colon normal colon tumor GW98-177 22060 35 12.59 25.18 colon tumor -1.10 colon normal GW98-561 23514 35.48 9.4 18.80 colon normal colon tumor GW98-560 23513 36.2 16.14 12.28 colon tumor -1.53 colon normal GW98-894 24691 34.53 116.62 33.24 colon normal colon tumor GW98-893 24690 34.29 19.25 38.50 colon tumor 1.16 lung normal GW98-3 20742 34.53 16.69 33.38 lung normal lung tumor GW98-2 20741 37.87 2.25 4.50 lung tumor -7.42 lung normal GW97-179 120677 34.59 16.02 32.04 lung normal lung tumor GW97- 178 20676 34.45 17.43 34.86 lung tumor 1.09 lung normal GW98-165 21922 33.89 24.39 48.78 lung normal lung tumor GW98-164 21921 35.48 9.43 118.86 lung tumor -2.59 lung normal GW98-282 22584 36.67 4.62 9.24 lung normal lung tumor GW98-281 22583 37.87 2.26 4.52 lung tumor -2.04 breast normal GWOO- 28750 34.17 20.64 20.64 breast normal 392 breast tumor GWOO-391 28746 33.54 '30.09 160.18 breast tumor 2.92 breast normal GWOO- 28798 39.05 1.11 1.11 breast normal 413 breast tumor GWOO-412 28797 35.01 12.46 24.92 breast tumor 22.45 breast normal GWOO- 27592-95 40 0.55 0.55 breast normal .235:238 2.2 brat umr 218 breast tumor GWOO- 27588-9 1 35.07 12.02 1.2 bes uo 18 23 1:234 breast normal GW98- 23656 33 41.58 183.16 breast normal 621 breast tumor GW98-620 23655 33.05 40.47 80.94 breast tumor -1.03 brain normal BB99-542 25507 32.73 48.93 97.86 brain normal brain normal BB99-406 25509 33.97 23.34 4.8 brain normal brain normal BB99-904 25546 137.88 2.24 4.48 brain normal brain stage 5 ALZ 25502 35.92 17.25 14.50 brain stage 5 ALZ -3.43 B1399-874 brain stage 5 ALZ 25503 31.57 97.99 1195.98 brain stage 5 ALZ 3.95 brain stage 5 ALZ 25504 36.08 6.57 113.14 brain stage 5 ALZ -3.78 BB99-862 brain stage 5 ALZ 25542 32.66 50.98 101.96 brain stage 5 ALZ 2.05 BB99-927 I__I

__I

CT lung KC Inormal 137.37 3.04 6.08 -1CT lung_____ lung 26 KG normal lung 26 lung 27 KG normal 138.52 11.52 11.52 lung 27 lung 24 KG COPD 40 0 10.00 lung 24 -3.07 lung 28 KC COPD 37.4 2.99 2.99 lung 28-1.03 lung 23 KC COPD 39.56 0.82 0.82 lug 23 1-3.74 lung 25 KG normal 38.43 1.61 1.61 lung i asthmatic lung 29321 39.45 0.88 0.88 asthmatic lung -3.49 OD03112 asthmatic lung 29323 36.48 5.19 10.38 asthmatic lung 3.38 OD03433____ asthmatic lung 29322 35.56 8.99 17.98 asthmatic lung 5.86 OD03397 asthmatic lung 29325 37.06 3.66 7.32 asthmatic lung 2.38 OD04928 endo cells KC control 39.29 0.96 0.96 endo cells endo VEGF KC 37.65 2.57 2.57 endo VEGF 2.68 endo bFGF KC 40 0.48 0.48 endo bFGF -2.00 heart Clontech normal 40 0.68 1.36 heart heart T-1 ischemic 29417 39.29 0.96 1.92 heart T-1 1.41 heart (T-14) non- 29422 38.21 1.84 3.68 heart T-14 2.71 obstructive DCM heart (T-3399) DCM 29426 35.49 9.35 18.70 heart T-3399 13.75 adenoid GW99-269 26162 39.63 0.78 1.56 adenoid tonsil GW98-280 22582 34.5 16.92 33.84 tonsil T cells PC00314 28453 34.57 16.25 32.50 T cells PBMNC 37.32 3.13 3.13 PBMNC monocyte 37.74 2.44 4.88 monocyte B cells PC00665 28455 33.32 34.36 68.72 B cells dendritic cells 28441 37.29 3.19 6.38 dendritic cells neutrophils 28440 36.01 6.85 6.85 neutrophils eosinophils 28446 35.38 9.98 19.96 eosinophils BM unstim 37.44 2.91 2.91 BM unstim BM stim 40 0.53 0.53 BM stim -5.49 osteo dif 38.15 1.91 1.91 osteodif -1.38 osteo undif 37.6 2.64 2.64 osteo undif chondrocytes 36.1 6.51 16.28 chondrocytes OA Synovium IP12/01 29462 35.58 8.86 8.86 OA Synovium OA Synovium NP10/01 29461 35.46 9.54 19.08 OA Synovium OA Synovium NP57/00 28464 34.05 22.23 44.46 OA Synovium RA Synovium NP03/01 28466 37.92 2.19 4.38 RA Synovium RA Synovium NP71/00 28467 35.39 9.92 19.84 RA Synovium RA Synovium NP45/00 28475 35.03 12.37 24.74 RA Synovium OA bone (biobank) 29217 39.98 0.67 0.67 OA bone (biobank) OA bone Sample 1 J. Emory 36.06 6.68 13.36 OA bone OA bone Sample 2 J. Emory 39.89 0.67 1.34 OA bone Cartilage (pool) Normal 35.57 8.92 17.84 Cartilage (pool) Cartilage (pool) OA 39.5 0.85 1.70 Cartilage (pool) -10.49 PBL unifected 28441 36.65 4.67 9.34 PBL unifected PBL MIV IIB 28442 36.94 3.92 7.84 PBL HIV IIB -1.19 uninfected 29158 37.54 2.74 5.48 MRC5 uninfected (100%) HSV strain F 29178 33.19 37.18 74.36 MRC5 HSV strain 13.57 W12cells 29179 37.23 3.3 6.60 W12 cells Keratinocytes 29180 37.18 3.4 6.80 Keratinocytes B-actin control 27.26 1296.8 genomic 27.2 1345.3 4 l.00E+05 19.44 100000 1.OOE+05 100000 l.OOE+04 10000 1.00E+04 23.41 10000 1.OOE+03 27.77 1000 1.00E+03 27.89 1000 1.OOE+02 32.32 100 1 .OOE+02 32.3 100 1.OOE+01 36.77 10 1.00E+01 36.39 10 1.OOE-00 38.06 1 1.OOE-00 1 NTC 1-1 Gene Name sbglO15258PLM Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.17 colon tumor -1.10 colon tumor -1.53 colon tumor 1.16 lung tumor -7.42 lung tumor 1.09 lung tumor -2.59 lung tumor -2.04 breast tumor .2.92 breast tumor 22.45 breast tumor 21.85 breast tumor -1.03 brain stage 5 ALZ -3.43 brain stage 5 ALZ 3.95 brain stage 5 ALZ7-37 brain stage 5 ALZ lung 24-30 lung 28-10 lung 23-37 asthmatic lung-34 asthmatic lung 33 asthmatic lung 5.86 asthmatic lung 2.38 endo VEGF 2.68 endo bFGF 1-2.00 heart T- 1 1.41 heart T-14 i2.71 heart T-3399 13.75 BM stim -5.49 osteo dif -1.38 Cartilage (pool) -10.49 PBL HIV HIIB -1.19 HSV strain F 13.57 Gene Name sbg1003328IG (Taqman) Moderate overall expression. Highest normal expression in whole brain, fetal brain, and cerebellum with slightly lower levels of expression in the colon and mammary gland. Highest disease expression in the colon and lung tumor pairs as well as the normal and Alzheimer's brain.

Significant upregulation in 2 of 4 breast tumor samples with slight upregulation in 1 of 4 breast tumor samples implicates this gene in breast cancer. Downregulation in 3 of 3 COPD samples may suggest an involvement in chronic obstructive pulmonary disease. Downregulation in 1 of 4 asthma samples suggests a potential role for this gene in asthma. Downregulation in the HSV-infected MRC5 cells suggests that this gene may play a role in HSV. High expression in 3 of 3 OA synovium samples, 3 of 3 RA synovium samples, 2 of 2 OA bone samples, and corroborating high expression in the T cells and B cells implicates this gene in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Average 18S 50 copies sbgl003328IG 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detected 1) 2) /50 ng total

__RNA

Subcutaneous 32.35,32.1 109.15 127.12 118.14 3.06 16.34 1930.31 Adipocytes Zenbio Subcutaneous Adipose 37.92,40 3.84 0 1.92 0.96 52.36 100.52 Zenbio Adrenal Gland 38.07, 35.73 3.5 14.32 8.91 0.61 81.97 730.33 Clontech Whole Brain Clontech 22.72,23.09 35640.5 28576.52 32108.51 7.24 6.91 221743.

Fetal Brain Clontech 33.39, 34.06 58.43 39.04 48.74 0.48 103.95 5066.01 Cerebellum Clontech 31.32, 31.02 202.49 242.95 222.72 2.17 23.04 5131.80 Cervix 36.36, 35.6 9.78 15.49 12.64 2.42 20.66 261.05 Colon 30.74,32.11 286.9 125.78 206.34 2.71 18.45 3807.01 Endometrium 34.58, 36.01 28.47 12.11 20.29 0.73 68.21 1384.04 Esophagus 37.54,36.05 4.82 11.78 8.30 1.37 36.50 302.92 Heart Clontech 36.23, 36.85 10.56 7.3 18.93 1.32 37.88 338.26 Hypothalamus 40,36.96 0 6.81 3.41 0.32 155.28 528.73 Ileum 34.79,34.48 25.09 30.4 27.75 2.58 19.38 537.69 Jejunum 30.14,31.02 412.72 242.47 327.60 6.60 7.58 2481.78 Kidney 33.94,34.61 41.89 28.12 35.01 2.12 23.58 825.59 Liver 36.11,35.38 11.41 17.61 14.51 1.50 33.33 483.67 Fetal Liver Clontech 30.24,30.27 388.12 381.28 384.70 10.40 4.81 1849.52 Lung 35.59, 35.09 15.59 20.98 18.29 2.57 19.46 355.74 Mammary Gland 29.21,28.52 718.74 1090.18 904.46 13.00 3.85 3478.69 Clontech Myometrium 33.7,34.11 48.42 37.85 43.14 2.34 21.37 921.69 Omentum 33.83, 33.57 44.75 52.27 48.51 3.94 12.69 615.61 Ovary 32.47,32.34 101.42 109.96 105.69 4.34 11.52 1217.63 Pancreas 38.16,40 3.31 0 1.66 0.81 61.80 102.29 Head of Pancreas 40, 36.68 0 8.07 4.04 1.57 31.85 128.50 Parotid Gland 31.68, 31.03 162.92 241.11 202.02 5.48 9.12 1843.20 Placenta Clontech 30.48, 30.82 335.37 274.53 304.95 5.26 9.51 2898.76 Prostate 33.39, 32.15 58.39 122.82 90.61 3.00 16.67 1510.08 Rectum 35.95, 35.32 12.5 18.32 15.41 1.23 40.65 626.42 Salivary Gland 31.25, 30.65 211.88 303.2 257.54 7.31 6.84 1761.56 Clontech Skeletal Muscle 36.61, 37.62 8.44 4.6 6.52 1.26 39.68 258.73 Clontech Skin 36.37,36.08 9.71 11.56 10.64 1.21 41.32 439.46 Small Intestine 36.74,34.51 7.79 29.79 18.79 0.98 51.07 959.65 Clontech Spleen 34.78,35.63 25.25 15.18 20.22 4.92 10.16 205.44 Stomach 40,35.13 0.88 20.56 10.72 2.73 18.32 196.34 Testis Clontech 35.01, 39.68 22.07 1.33 11.70 0.57 87.87 1028.12 Thymus Clontech 29.15,29.2 749.23 724.61 736.92 9.89 5.06 3725.58 Thyroid 32.02, 32.14 133.23 123.77 128.50 2.77 18.05 2319.49 Trachea Clontech 31.28, 30.17 207.67 405.04 306.36 9.71 5.15 1577.52 Urinary Bladder 33.07, 32.91 70.6 78.07 74.34 5.47 9.14 679.48 Uterus 33.01, 33.15 73.56 67.48 70.52 5.34 9.36 660.30 genomic 29.15 746.77 b-actin 30.2 397.52 1.00E+05 21.06 100000 1.00E+05 20.94 100000 1.00E+04 25.06 10000_____ 1.00E+04 24.54 10000 1.00E+03 28.32 1000 1.00E+03 28.77 1000 1.00E+02 33 100 1.00E+02 32.74 1.00E+01 35.9 10 1.00E+01 40 0 1.00E-00 40 0 1.00E-00 40 NTC 40 NTC 40 Sample Reg Ct Mean copies of Sample Fold sbg10033281G number GOI mRNA Change (GSK copies detected/ in identifie 50 ng Disease r) total Populati RNA on colon normal GW98-167 21941 24.26 15509.01 31018.02 colon normal colon tumor GW98-166 21940 24.5 13727.44 27454.88 colon tumor -1.13 colon normal GW98- 178 22080 28.01 2276.97 4553.94 colon normal colon tumor GW98- 177 22060 27.11 3618.2 7236.40 colon tumor 1.59 colon normal GW98-561 23514 24.47 13993.67 27987.34 colon normal colon tumor GW98-560 23513 25.32 19040.47 18080.94 colon tumor -1.55 colon normal GW98-894 24691 24.17 16251.61 32503.22 colon normal colon tumor GW98-893 24690 25.15 9872.46 19744.92 colon tumor -1.65 lung normal GW98-3 20742 24.4 14498.52 28997.04 lung normal lung tumor GW98-2 20741 24.66 12640.32 25280.64 lung tumor -1.15 lung normal GW97-179 20677 24.12 16680.84 133361.68 lung normal lung tumor GW97- 178 20676 24.69 12468.91 24937.82 lung tulmor -1.34 lung normal GW98-165 21922 25.09 10168.18 20336.36 lung normal lung tumor GW98-164 21921 25.49 8296.37 16592.74 lung tumor -1.23 lung normal GW98-282 22584 26.85 4131.52 8263.04 lung normal lung tumor GW98-281 22583 26.59 14702 9404.00 lung tumor 1.14 breast normal GWOO- 28750 25.9 6719.98 6719.98 breast normal 392 breast tumor GWOO-391 28746 25.04 10402.11 20804.22 breast tumor 3.10 breast normal GWOO- 28798 32.51 226.94 226.94 breast normal 413 breast tumor GWOO-412 28797 26.37 5261.73 10523.46 breast tumor 46.37 breast normal GWOO- 27592- 34.58 78.63 78.63 breast normal 235:238 95 breast tumor GWOO- 27588- 28.45 1812.86 1812.86 breast tumor 23.06 231:234 91 breast normal GW98- 23656 25.26 9289.36 18578.72 breast normal 621 breast tumor GW98-620 23655 25.66 7579.13 15158.26 breast tumor -1.23 brain normal BB99-542 25507 22.52- 37845.47 75690.94 brain normal brain normal BB99-406 25509 23.07 28574.8 57149.60 brain normal brain normal BB99-904 25546 23.85 19214.49 38428.98 brain normal brain stage 5 ALZ 25502 25.98 6442.51 12885.02 brain stage 5 ALZ -4.43 BB99-874 brain stage 5 ALZ 25503 23.19 26936.06 53872.12 brain stage 5 ALZ -1.06 brain stage 5 ALZ 25504 23.42 23948.83 47897.66 brain stage 5 ALZ -1.19 BB99-862____ brain stage 5 ALZ 25542 24.15 16419.33 32838.66 brain stage 5 ALZ -1.74 BB99-927 CT lung KC normal 25.63 7714.35 15428.70 CT lung lung 26 KC normal 32.34 247.99 1247.99 lung 26 lung 27 KC normal 33.71 122.77 1122.77 lung 27 lung 24 KC COPD 32.47 231.47 231.47 lung 24 -17.21 lung 28 KC COPD 32.63 213.14 213.14 lung 28 -18.70 lung 23 KC COPD 131.2 444.95 444.95 lung 23 -8.96 lung 25 KC normal 33.46 139.4 139.40 lung 25 asthmatic lung 29321 31.6 360.95 360.95 asthmatic lung -11.04 OD03 112 asthmatic lung 29323 28.66 1634.71 3269.42 asthmatic lung -1.22 0D03433 asthmatic lung 129322 126.36 5294.26 10588.52 asthmatic lung 2.-66 1 OD03397 asthmatic lung 29325 28.23 2033.93 4067.86 asthmatic lung 1.02 OD04928 endo cells KC control 30.68 580.47 580.47 endo cells endo VEGF KC 31.08 471.26 471.26 endo VEGF -1.23 endo bFGF KC 32.25 259.04 259.04 endo bFGF -2.24 heart Clontech normal 27.28 3312.82 6625.64 heart heart (T-1 ischemic 29417 27.48 2979.22 5958.44 heart T-1 -1.11 heart (T-14) non- 29422 27.74 2613.8 5227.60 heart T-14 -1.27 obstructive DCM heart (T-3399) DCM 29426 26.66 4541.38 9082.76 heart T-3399 1.37 adenoid GW99-269 26162 27.83 2493.31 4986.62 adenoid tonsil GW98-280 22582 25.68 7506.04 15012.08 tonsil T cells PC00314 28453 27.18 3487.61 6975.22 T cells PBMNC 32.6 216.73 216.73 PBMNC monocyte 32.27 256.89 513.78 monocyte B cells PC00665 28455 27.83 2492.12 4984.24 B cells dendritic cells 28441 26.67 4528.97 9057.94 dendritic cells neutrophils 28440 28.4 1862.35 1862.35 neutrophils eosinophils 28446 31.69 344.59 689.18 eosinophils BM unstim 32.04 289.03 289.03 BM unstim BM stim 30.59 607.18 607.18 BM stim 2.10 osteo dif 28.43 1831.57 1831.57 osteo dif 3.42 osteo undif 30.83 536 536.00 osteo undif chondrocytes 26.74 4368.46 10921.15 chondrocytes OA Synovium IP12/01 29462 27.91 2391.03 2391.03 OA Synovium OA Synovium NP10/01 29461, 27.4 3109.93 6219.86 OA Synovium OA Synovium NP57/00 28464 27.05 3729.47 7458.94 OA Synovium RA Synovium NP03/01 28466 25.53 8116.96 16233.92 RA Synovium RA Synovium NP71/00 28467 26.06 6167.42 12334.84 RA Synovium RA Synovium NP45/00 28475 25.35 8888.66 17777.32 RA Synovium OA bone (biobank) 29217 30.23 729.87 729.87 OA bone (biobank) OA bone Sample 1 J. Emory 27.65 2743.38 5486.76 OA bone OA bone Sample 2 J. Emory 28.02 2258.96 4517.92 OA bone Cartilage (pool) Normal 25.82 7006.64 14013.28 Cartilage (pool) Cartilage (pool) OA 27.22 3408.61 6817.22 Cartilage (pool) -2.06 PBL unifected 28441 24.24 15680.49 31360.98 PBL unifected PBL HIV IB 28442 25.43 8521.98 17043.96 PBL HIV IIIB -1.84 uninfected 29158 25.58 7922.19 15844.38 MRC5 uninfected (100%) 100%) HSV strain F 29178 32.02 291.12 582.24 MRC5 HSV strain -27.21

F

W12 cells 29179 26.03 6269.24 12538.48 W12 cells Keratinocytes 29180 25.43 8538.15 17076.30 Keratinocytes B-actin control 29.74 938.61 genomic 28.79 1522.16 1.00E+05 20.84 100000 1.00E+05 21.4 100000 1.OOE+04 24510000 l.OOE+04 25.2 10000 l.OOE+03 28.45 1000 1.00E+03 29.25 1000 l.00E+02 3R5.3 4 100 L.OOE+02 100 1.0012+01 38.95 10 L.OOE+01 0 1.OOE-00 140 0 1.OOE-00 140 10 INTC 140 10 Gene Name sbg10033281G Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -1.13 colon tumor 1.59 colon tumor -1.55 colon tumor -1.65 lung tumor -1.15 lung tumor -1.34 lung tumor -1.23 lung tumor 1.14 breast tumor 3.10 breast tumor 46.37 breast tumor 23.06 breast tumor -1.23 brain stage 5 ALZ -4.43 brain stage ALZ -1.06 brain stage 5 ALZ 1-1.19 brain stage 5ALZ -1.74 lung 24 -17.21 lung 28 -18.70 lung 23 -8.96 asthmatic lung -11.04 asthmatic lung -1.22 asthmatic lung 2.66 asthmatic lung 1.02 endo VEGF -1.23 endo bFGF -2.24 heart T- 1 -1.11 heart T- 14 -1.27 heart T-3399 1.37 EM stim 2.10 osteo dif 3.42 Cartilage (pool) -2.06 PBL HV IIIB -1.84 HSV strain F -27.21 Gene Name sbg1020829SGLT Low overall expression in normal and disease samples. Highest normal expression in the whole brain, kidney, and thymus. Highest disease expression in the adenoid, tonsil, T cells, B cells, and eosinophils. Highly immune cell specific. Downregulation in 1 of 4 lung tumor samples and upregulation in 1 of 4 breast tumor samples indicates involvement in cancers of the lung and breast. Upregulation in 3 of 4 AD brain samples suggests an involvement in Alzheimer's disease.

Downregulation in 3 of 3 COPD samples implies a role in chronic obstructive pulmonary disease. Downregulation in the stimulated bone marrow sample. Upregulation in the differentiated osteoblast sample. Upregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. Moderate to high expression in the OA and RA samples indicates a potential role in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg1020829SGLT 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 37.07,40 7.33 0 3.67 3.06 16.34 59.89 Adipocytes Zenbio Subcutaneous Adipose 40, 40 0 0 0.00 0.96 52.36 0.00 Zenbio Adrenal Gland Clontech 40,40 0 0 0.00 0.61 81.97 0.00 Whole Brain Clontech 32.13, 32.38 138.5 119.48 128.99 7.24 6.91 890.81 Fetal Brain Clontech 40,40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 40,40 0 0 0.00 2.17 23.04 0.00 Cervix 36.13,40 12.82 0 6.41 2.42 20.66 132.44 Colon 36.93, 36.84 7.97 8.41 8.19 2.71 18.45 151.11 Endometrium 37.45,37.41 5.84 5.98 5.91 0.73 68.21 403.14 Esophagus 40,40 0 0 0.00 1.37 36.50 0.00 Heart Clontech 40, 40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40,40 0 0 0.00 0.32 155.28 0.00 Ieum 36.53, 35.17 10.09 22.67 16.38 2.58 19.38 317.44 Jejunum 40, 35.73 0 16.2 8.10 6.60 7.58 61.36 Kidney 31.93,31.01 155.27 269.39 212.33 2.12 23.58 5007.78 Liver 36.1, 35.88 13.05 14.82 13.94 1.50 33.33 464.50 Fetal Liver Clontech 35.06, 34.36 24.26 36.78 30.52 10.40 4.81 146.73 Lung 37.24, 40 6.63 0 3.32 2.57 19.46 64.49 Mammary Gland 34.25, 34.21 39.27 40.17 39.72 13.00 3.85 152.77 Clontech Myometrium 38.48, 35.31 3.16 20.87 12.02 2.34 21.37 256.73 Omentum 40, 38.91 0 2.45 1.23 3.94 12.69 15.55 Ovary 37.87, 37.06 4.56 7.37 5.97 4.34 11.52 68.72 Pancreas 40, 40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40, 40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 36.06, 37.07 13.32 7.31 10.32 5.48 9.12 94.11 Placenta Clontech 35.98, 38.73 13.96 2.72 8.34 5.26 9.51 79.28 Prostate 40,40 0 0 0.00 3.00 16.67 0.00 Rectum 40,40 0 0 0.00 1.23 40.65 0.00 Salivary Gland 37.05, 37.06 7.4 7.36 7.38 7.31 6.84 50.48 Clontech Skeletal Muscle 40,40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 40,40 0 0 0.00 1.21 41.32 0.00 Small Intestine 40, 40 0 0 0.00 0.98 51.07 0.00 Clontech Spleen 35.62, 35.72 17.34 16.35 16.85 4.92 10.16 171.19 Stomach 40, 40 0 1.61 0.81 2.73 18.32 14.74 Testis Clontech 40, 40 0 0 10.00 0.57 87.87 0.00 Thymus Clontech 31.3, 31.09 226.24 257.15 241.70 9.89 5.06 1221.92 Thyroid 40, 40 0 0 0.00 2.77 18.05 0.00 Trachea Clontech 36.6,36.64 9.68 9.44 9.56 9.71 5.15 49.23 Urinary Bladder 40,40 0 0 0.00 5.47 9.14 0.00 Uterus 34.64,36.65 31.06 9.41 20.24 5.34 9.36 189.47 genomic 29.07 b-actin 27.08 1.00E+05 20.85 100000 1.00E+05 21.11 100000 1.00E+04 24.81 10000_____ 1.00E+04 24.95 1.00E+03 28.39 1000 1.00E+03 28.9 1000_____ 1.00E+02 34.1 1.00E+02 32.86 1.00E+01 35.52 1.00E+01 40 0 1.00E-00 40 1.00E-00 40 NTC 40 NTC 40 Sample Reg Ct Mean copies of Sample Fold sbg1020829SGLT number GOI mRNA Change (GSK copies detected/ in identifier 50 ng Disease total Populat RNA ion colon normal GW98-167 21941 31.06 206.55 413.10 colon normal colon tumor GW98-166 21940 31.18 193.59 387.18 colon tumor -1.07 colon normal GW98-178 22080 30.74 244.37 488.74 colon normal colon tumor GW98-177 22060 30.37 299.28 598.56 colon tumor 1.22 colon normal GW98-561 23514 29.31 527.04 1054.08 colon normal colon tumor GW98-560 23513 31.86 134.48 268.96 colon tumor -3.92 colon normal GW98-894 24691 31.84 135.33 270.66 colon normal colon tumor GW98-893 24690 31.9 131.57 263.14 colon tumor -1.03 lung normal GW98-3 20742 28.81 689.14 1378.28 lung normal lung tumor GW98-2 20741 31.91 130.71 261.42 lung tumor -5.27 lung normal GW97-179 20677 30.04 356.26 1712.52 lung norma]l___ lung tumor GW97- 178 20676 29.05 605.73 1211.46 lung tumor 1.70 lung normal GW98-165 21922 28.42 852.41 1704.82 lung normal____ lung tumor GW98-164 21921 30.51 277.13 554.26 lung tumor -3.08 lung normal GW98-282 22584 31.23 188.34 376.68 lung normal lung tumor GW98-281 22583 30.46 285 570.00 lung tumor 1.51 breast normal GWOO-392 28750 31.14 197.15 197.15 breast normal breast tumor GWOO-391 28746 32.15 114.65 229.30 breast tumor 1.16 breast normal GWOO-413 28798 34.87 26.64 26.64 breast normal breast tumor GWOO-412 28797 31.83 136.42 272.84 breast tumor 10.24 breast normal GWOO- 27592-95 36.34 12.09 12.09 breast normal 235:238 breast tumor GW0O- 27588-91 33.48 56.11 156.11 breast tumor 4.64 231:234 breast normal GW98-621 23656 32.39 100.78 1201.56 breast normal breast tumor GW98-620 23655 31.4 171.82 343.64 breast tumor 1.70 brain normal BB99-542 25507 34.49 32.75 65.50 brain normal brain normal BB99-406 25509 34.01 42.2 84.40 brain normal brain normal BB99-904 25546 36.17 13.3 26.60 brain normal brain stage 5 ALZ BB99- 25502 31.16 195.23 390.46 brain stage 5 ALZ 6.64 874 brain stage 5 ALZ BB99- 25503 31.56 157.33 314.66 brain stage 5 ALZ 5.35 887 brain stage 5 ALZ BB99- 25504 32.62 89.2 178.40 brain stage 5 ALZ 3.03 862 brain stage 5 ALZ B1399- 25542 33.26 63.43 126.86 brain stage 5 ALZ 2.16 927 CT lung KC normal 30.82 234.88. 1469.76 CT lung lung 26 KC normal 30.21 325.42 325.42 lung 26 lung 27 KC normal 36.89 9 9.00 lung 27 lung 24 KC COPD 36.17 13.24 13.24 lung 24 -15.84 lung 28 KC COPD 38.38 4.06 4.06 lung 28 -51.66 lung 23 KC CQPD 35.53 189.67 18.67 lung 23 -11.23 lung 25 KC normal 34.37 34.83 34.83 lung asthmatic lung OD031 12 29321 33.65 51.41 51.41 asthmatic lung -4.08 asthmatic lung 0D03433 29323 30.62 260.95 521.90 asthmatic lung 2.49 asthmatic lung 0D03397 29322 31.31 180.14 1360.28 asthmatic lung 1.72 asthmatic lung 0D04928 29325 31.14 197.09 394.18 asthmatic lung 1.88 endo, cells KC control 32.56 92.23 '92.2 endo cells endo VEGF KC 33.29 62.39 62.39 endo VEOF -1.48 endo bFGF KC 92.65 92.65 endo bFGF 1.00 heart Clontech normal 33.17 66.25 1132.50 heart heart (T-lI ischemic 29417 33.07 70.16 1140.32 heart T-1 1.06 heart (T-14) non- 29422 34.64 30.13 60.26 heart T- 14-20 obstructive DCM I heart (T-3399) DCM 129426 132.53 93.63 187.26 heart T-3399 14 adenoid GW99-269 26162 28.92 650.55 1301.10 adenoid tonsil GW98-280 22582 27.11 1719.42 3438.84 tonsil T cells PC00314 28453 28.05 1037.04 2074.08 T cells PBMNC 36.57 10.71 10.71 PBMNC monocyte 33.22 64.68 129.36 monocyte B cells PC00665 28455 27.07 1757.79 3515.58 B cells dendritic cells 28441 33.77 48.05 96.10 dendritic cells neutrophils 28440 30.71 248.56 248.56 neutrophils eosinophils 28446 27.3 1549.7 3099.40 eosinophils BM unstim 30.06 352.26 352.26 BM unstim BM stim 34.14 39.39 39.39 BM stim -8.94 osteo dif 36.29 12.42 12.42 osteo dif 12.42 osteo undif 40 0 0.00 osteo undif chondrocytes 32.11 117.39 293.48 chondrocytes OA Synovium IP12/01 29462 30.17 331.7 331.70 OA Synovium OA Synovium NP10/01 29461 32.05 120.98 241.96 OA Synovium OA Synovium NP57/00 28464 30.13 339.03 678.06 OA Synovium RA Synovium NPO3/01 28466 31.28 182.96 365.92 RA Synovium RA Synovium NP71/00 28467 29.81 402.34 804.68 RA Synovium RA Synovium NP45/00 28475 30.22 324.14 648.28 RA Synovium OA bone (biobank) 29217 28.45 837.78 837.78 OA bone (biobank) OA bone Sample 1 J. Emory 30.21 325.03 650.06 OA bone OA bone Sample 2 J. Emory 29.8 406 812.00 OA bone Cartilage (pool) Normal 31.09 203.28 406.56 Cartilage (pool) Cartilage (pool) OA 32.18 112.77 225.54 Cartilage (pool) -1.80 PBL unifected 28441 29.17 567.22 1134.44 PBL unifected PBL HIV IIIB 28442 30.73 246.69 493.38 PBL HIV IIIB -2.30 MRCS uninfected 29158 35.54 18.61 37.22 MRC5 uninfected (100%) (100%) HSV strain F 29178 30.54 272.3 544.60 MRC5 HSV strain 14.63 1 F W12 cells 29179 32.28 107.25 214.50 W12 cells Keratinocytes 29180 34.27 36.84 73.68 Keratinocytes B-actin control 27.03 1793.92 genomic 27.77 1204.8 1.00E+05 19.84 100000 1.00E+05 19.86 100000 1.00E+04 23.46 10000 1.00E+04 23.8 10000 1.00E+03 27.45 1000 1.00E+03 27.94 1000 1.00E+02 33.86 100 1.00E+02 31.41 100 1.00E+01 40 0 1.00E+01 36.88 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 Gene Name sbg1020829SGLT Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -1.07 colon tumor 1.22 colon tumor -3.92 colon tumor -1.03 lung tumor -5.27 lung tumor 1.70 lung tumor -3.08 lung tumor 1.51 breast tumor 1.16 breast tumor 10.24 breast tumor 4.64 breast tumor 1.70 brain stage 5 ALZ 6.64 brain stage 5 ALZ 5.35 brain stage 5 ALZ 3.03 brain stage 5 ALZ 2.16 lung 24 -15.84 lung 28 -51.66 lung 23 -11.23 asthmatic lung -4.08 asthmatic lung 2.49 asthmatic lung 1.72 asthmatic lung 1.88 endo VEGF -1.48 endo bFGF 1.00 heart T-1 1.06 heart T- 14 -2.20 heart T-3399 1.41 BM stim -8.94 osteo dif 12.42 Cartilage (pool) -1.80 PBL HIV MIB -2.30 HSV strain F 14.63 Gene Name sbgI005450UDPGT Low to moderate overall expression. Highest normal expression in endometrium, esophagus, and spleen with lower levels of expression in cerebellum, hypothalamus, rectum, and uterus. Highest disease expression in one of the OA synovium samples. Downregulation in 1 of 4 colon tumor samples is sufficient to make a disease claim in cancer of the colon. Upregulation in 1 of 4 lung tumor samples indicates a potential role for this gene in cancer of the lung. Downregulation in 2 of 4 AD brain samples suggests an involvement in Alzheimer's disease. Downregulation in 3 of 3 COPD lung samples and 4 of 4 asthmatic lung samples suggests involvement in chronic obstructive pulmonary disease and asthma. Upregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. Moderate expression in the B cells and the dendritic cells.

Sample Ct Mean Mean Averag 18S 50 copies sbgI005450UDPGT (sample 1 GOI GOI e GOI rRNA ng/18S of and 2) copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total Subcutaneous 40,40 0.15 0.17 0.16 3.06 16.34 2.61 Adipocytes Subcutaneous Adipose 40,40 0 0 0.00 0.96 52.36 0.00 Zenbio Adrenal Gland 40,40 0 0.14 0.07 0.61 81.97 5.74 Clontech Whole Brain Clontech 33.74,40 12.07 0 6.04 7.24 6.91 41.68 Fetal Brain Clontech 40,40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 32.07, 33.2 32.85 16.64 24.75 2.17 23.04 570.16 Cervix 40,40 0 0 0.00 2.42 20.66 0.00 Colon 40, 35.16 0 5.12 2.56 2.71 18.45 47.23 Endometrium 32.73, 31.85 22.19 37.5 29.85 0.73 68.21 2035.81 Esophagus 32.67, 29.39 22.91 165.34 94.13 1.37 36.50 3435.22 Heart Clontech 37.12, 35.03 1.58 5.55 3.57 1.32 37.88 135.04 Hypothalamus 34.08, 40 9.84 0 4.92 0.32 155.28 763.98 Ileum 34.35 8.33 8.33 2.58 19.38 161.43 Jejunum 40,40 0 0 0.00 6.60 7.58 0.00 Kidney 38.89,40 0.54 0 0.27 2.12 23.58 6.37 Liver 36.32, 40 2.55 0 1.28 1.50 33.33 42.50 Fetal Liver Clontech 36.96 1.74 1.74 10.40 4.81 8.37 Lung 40,40 0 0 0.00 2.57 19.46 0.00 Mammary Gland 40,40 0 0 0.00 13.00 3.85 0.00 Clontech Myometrium 40,38.22 0 0.82 0.41 2.34 21.37 8.76 Omentum 36.17,40 2.8 0 1.40 3.94 12.69 17.77 Ovary 40,40 0 0 0.00 4.34 11.52 0.00 Pancreas 40,40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40,38.35 0 0.75 0.38 1.57 31.85 11.94 Parotid Gland 40,40 0 0 0.00 5.48 9.12 0.00 Placenta Clontech 39.06, 35.49 0.49 4.22 2.36 5.26 9.51 22.39 Prostate 38.81,40 0.57 0 0.29 3.00 16.67 4.75 Rectum 35.22, 33.25 4.94 16.2 10.57 1.23 40.65 429.67 Salivary Gland 32.56,34.56 24.55 7.36 15.96 7.31 6.84 109.13 Clontech Skeletal Muscle 40,40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 34.26,40 8.8 0 4.40 1.21 41.32 181.82 Small Intestine 40 0 6.23 3.12 0.98 51.07 159.09 Spleen 40,27.36 0 560.92 280.46 4.92 10.16 2850.20 Stomach 33.49,39.12 13.98 0.47 7.23 2.73 18.32 132.33 Testis Clontech 40, 40 0 0 0.00 0.57 87.87 0.00 Thymus Clontech 40,35.33 0 4.64 2.32 9.89 5.06 11.73 Thyroid 37.18, 35.52 1.53 4.13 2.83 2.77 18.05 51.08 Trachea Clontech 40,40 0 0 0.00 9.71 5.15 0.00 Urinary Bladder 40,40 0 0.16 0.08 5.47 9.14 0.73 Uterus 30.11 106.94 0 53.47 5.34 9.36 500.66 genomic 35.81 b-actin 26.86 757.01 1.OOE+05 18.99 1.OOE+05 19.13 100000 1.OOE+04 22.43 1.OOE+04 22.31 1.00E+03 25.74 1.OOE+03 25.99 1.00E+02 31.47 1.00E+02 29.82 1.00E+01 40 0 1.00E+01 40 1.00E-00 40 1.00E-00 40 NTC 26.02 NTC 40 Sample Reg Ct Mean copies Sample Fold sbg1005450UDPGT number GOI of Change (GSK copies mRNA in identifie detecte Disease r) d/50 ng Populati total on colon normal GW98-167 21941 40 0.17 0.34 colon normal colon tumor GW98-166 21940 39.88 0.29 0.58 colon tumor 1.71 colon normal GW98-178 22080 40 0 0.00 colon normal colon tumor GW98-177 22060 40 0 0.00 colon tumor 0.00 colon normal GW98-561 23514 40 0 0.00 colon normal colon tumor GW98-560 23513 40 0 0.00 colon tumor 0.00 colon normal GW98-894 24691 33.84 10.47 20.94 colon normal colon tumor GW98-893 24690 40 0 0.00 colon tumor -20.94 lung normal GW98-3 20742 40 0 0.00 lung normal lung tumor GW98-2 20741 40 0 0.00 lung tumor 0.00 lung normal GW97-179 20677 31.67 37.94 75.88 lung normal lung tumor GW97-178 20676 33.08 16.47 32.94 lung tumor -2.30 lung normal GW98-165 21922 40 0 0.00 lung normal lung tumor GW98-164 21921 40 0 0.00 lung tumor 0.00 lung normal GW98-282 22584 40 0 0.00 lung normal lung tumor GW98-281 22583 35.03 5.16 10.32 lung tumor 10.32 breast normal GWOO-392 28750 32.64 21.38 21.38 breast normal breast tumor GWOO-391 28746 31.67 37.98 75.96 breast tumor 3.55 breast normal GWOO-413 28798 32.54 22.63 22.63 breast normal" breast tumor GWOO-412 28797 29.23 161.71 323.42 breast tumor 14.29 breast normal GWOO- 27592- 37.05 1.55 1.55 breast normal 235:238 breast tumor GWOO- 27588- 35.03 5.17 5.17 breast tumor 3.34 231:234 91 breast normal GW98-621 23656 34.12 8.87 17.74 breast normal breast tumor GW98-620 23655 40 0 0.00 breast tumor -17.74 brain normal BB99-542 25507 34.28 8.05 16.10 brain normal brain normal BB99-406 25509 40 0 0.00 brain normal brain normal BB99-904 25546 40 0 0.00 brain normal brain stage 5 ALZ BB99- 25502 38.8 0.55 1.10 brain stage 5 ALZ -4.88 brain stage 5 ALZ BB99- 25503 40 0 0.00 brain stage 5 ALZ -5.37 brain stage 5 ALZ BB99- 25504 36.16 2.64 5.28 brain stage 5 ALZ -1.02 brain stage 5 ALZ BB99- 25542 40 0 0.00 brain stage 5 ALZ -5.37 927 CT lung KC normal 36.61 2.02 4.04 CT lung lung 26 KC normal 26 lung 27 KC normal 40 0 0.00 lung 27 lung 24 KC COPD 40 0 0.00 lung 24 -1.35 lung 28 KC COPD 40 0 0.00 lung 28 -1.35 lung 23 KC COPD 40 0 0.00 lung 23 -1.35 lung 25 KC normal 40 0 0.00 lung 25 asthmatic lung OD03112 29321 38.19 0.79 0.79 asthmatic lung -1.70 asthmatic lung OD03433 29323 36.09 2.76 5.52 asthmatic lung 4.10 asthmatic lung OD03397 29322 40 0 0.00 asthmatic lung -1.35 asthmatic lung OD04928 29325 40 0 0.00 asthmatic lung ,-1.35 endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 40 0 0.00 endo bFGF 0.00 heart Clontech normal 40 0 0.00 heart heart (T-1 ischemic 29417 38.36 0.71 1.42 heart T-1 1.42 heart (T-14) non- 29422 40 0 0.00 heart T-14 0.00 obstructive DCM heart (T-3399) DCM 29426 40 0 0.00 heart T-3399 0.00 adenoid GW99-269 26162 38.96 0.5 1.00 adenoid tonsil GW98-280 22582 35.44 4.04 8.08 tonsil T cells PCO0314 28453 38.83 0.54 1.08 T cells PBMNC 40 0 0.00 PBMNC monocyte 35.1 4.94 9.88 monocyte____ B cells PC00665 28455 33.32 14.31 28.62 B cells dendritic cells 28441 32.53 22.85 45.70 dendritic cells neutrophils 28440 34.43 7.39 7.39 neutrophils eosinophils 28446 40 0 0.00 eosinophils BM unstim 40 0 0.00 BM unstim BMstim '34.12 8.87 8.87 BMstim 8.87 osteo dif 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 34.51 7.05 17.63 chondrocytes OA Synovium IP12/01 29462 40 0 0.00 OA Synovium OA Synovium NP0O/01 29461 27.21 538.51 1077.02 OA Synovium OA Synovium NP57/00 28464 33.5 12.85 25.70 OA Synovium RA Synovium NP03/01 28466 39.09 0.46 0.92 RA Synovium RA Synovium NP71/00 28467 40 0 0.00. RA Synovium RA Synovium NP45/00 28475 40 0 0.00 RA Synovium OA bone (biobank) 29217 40 0 0.00 OA bone I (biobank) OA bone Sample 1 J. Emory 35.23 4.59 9.18 OA bone OA bone Sample 2 J. Emory 37.1 1.51 3.02 OA bone Cartilage (pool) Normal 35.45 4.01 8.02 Cartilage (pool) Cartilage (pool) OA 40 0 0.00 Cartilage (pool) -8.02 PBL unifected 28441 40 0 0.00 PBL unifected PBL HIV IIIB 28442 40 0 0.00 PBL HIV IIIB 0.00 MRCS uninfected (100%) 29158 40 0.17 0.34 MRC5 uninfected (100%) HSV strain F 29178 30.15 93.76 187.52 MRC5 HSV strain 551.53

F

*W12 cells 29179 40 0 0.00 W12 cells Keratinocytes 29180 35.72 3.44 6.88 Keratinocytes B-actin control 26.57 788.4 genomic 25.69 1326.94 1.00E+05 18.72 100000 1.00E+05 18.74 100000 1.00E+04 22.11 10000 1.00E+04 22.15 10000 1.00E+03 25.57 1000 1.00E+03 25.54 1000 1.00E+02 31.37 100 1.00E+02 29.65 100 1.00E+01 40 0 1.00E+01 40 0 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 Gene Name sbg100545UDPGT Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.71 colon tumor 0.00 colon tumor 0.00 colon tumor -20.94 i lung tumor 0.00 lung tumor -2.30 lung tumor 0.00 lung tumor 10.32 breast tumor 3.55 breast tumor 14.29 breast tumor 3.34 breast tumor -17.74 brain stage 5 ALZ -4.88 brain stage 5 ALZ -5.37 brain stage 5 ALZ -1.02 brain stage 5 ALZ -5.37 lung 24 -1.35 lung 28 -1.35 lung 23 -1.35 asthmatic lung -1.70 asthmatic lung 4.10 asthmatic lung -1.35 asthmatic lung -1.35 endo VEGF 0.00 endo bFGF 0.00 heart T-1 1.42 heart T-14 0.00 heart T-3399 0.00 BM stim 8.87 osteo undif 0.00 Cartilage (pool) -8.02 PBL HIV IIIB 0.00 HSV strain F 551.53 Gene Name sbgl002620Tia Moderate overall expression. Highest normal expression in the whole brain, endometrium, myometrium, placenta, and rectum. Highest disease expression in the one of the colon normal/tumor pairs, the normal lung samples, one of the asthmatic lung samples, the neutrophils, the eosinophils, and one of the RA synovium samples. Expressed at high levels in all of the samples representative of the GI tract indicating a potential role for this gene in IBS, IBD, and Crohn's disease. Downregulation in 1 of 3 COPD lung samples suggests involvement in chronic obstructive pulmonary disease. Upregulation in 1 of 4 asthmatic lung samples implies a role in asthma. High expression in the OA synovium and bone samples as well as in the RA synovium samples. Also high expression in the chondrocytes. Variable expression in the immune cells with highest expression in the neutrophils and eosinophils and lowest expression in the dendritic cells.

Corroborating high expression in B and T cells as well as OA samples implicates this gene in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Average 18S 50 copies of sbg1002620TIa 1 and 2) GOI GOI GOI rRNA ng/18 mRNA copies copies Copies (ng) S detected/ (sample (sample rRNA 50 ng 1) 2) (ng) total

RNA

Subcutaneous 35.04, 34.4 201.66 274.43 1238.05 3.06 16.34 3889.62 Adipocytes Zenbia Subcutaneous Adipose 38.03, 38.45 48.67 39.85 44.26 0.96 52.36 2317.28 Zenbio Adrenal Gland Clontech 38.71, 38.14 35.25 46.23 40.74 0.61 81.97 3339.34 Whole Brain Clontech 29.27,29.32 3152.23 3071.49 3111.86 7.24 6.91 21490.75 Fetal Brain Clontech 40, 37.57 0 60.7 130.35 0.48 103.95 3154.89 Cerebellum Clontech 39.37, 39.14 25.78 28.75 27.27 2.17 23.04 628.23 Cervix 34.05, 34.32 323.57 285.02 304.30 2.42 20.66 6287.09 Colon 32.64, 32.98 633.12 537.54 585.33 2.71 18.45 110799.45 Endometrium 34.44,33.84 269.09 357.16 313.13 0.73 68.21 21359.14 Esophagus 35.48, 35.21 163.52 186.15 1174.84 1.37 36.50 6380.84 Heart Clontech 38.67, 39.08 35.94 29.52 132.73 1.32 37.88 1239.77 Hypothalamus 40, 40 0 0 0.00 0.32 155.28 0.00 Ileum 33.07, 32.9 516.19 559.94 538.07 2.58 19.38 110427.62 Jejunum 30.58, 30.66 1688.39 1625.61 1657.00 6.60 7.58 112553.03 Kidney 34.9, 33.68 216.07 385.19 300.63 12.12 23.58 17090.33 Liver 37.17,36.49 73.4 101.31 87.36 1.50 33.33 12911.83 Fetal Liver Clontech 33.99, 34.79 332.15 227.82 279.99 10.40 4.81 11346.08 Lung 34.67, 34.06 240.47 321.54 281.01 2.57 19.46 5467.02 Mammary Gland 29.3, 29.19 3098.36 3272.39 3185.38 13.00 3.85 12251.44 Clontech Myometrium 32.45, 31.79 692.54 946.75 819.65 2.34 21.37 17513.78 Omentum 32.88, 33.43 563.23 434.44 498.84 3.94 12.69 16330.39 Ovary 33.02, 32.92 528.43 553.26 540.85 4.34 11.52 16230.93 Pancreas 37.31, 39.81 68.49 20.84 44.67 0.81 61.80 12760.5 1.

Head of Pancreas 38.5, 39.16 38.99 28.45 33.72 1.57 31.85 11073.89 Parotid Gland 34.48, 34.22 263.15 298.49 280.82 5.48 9.12 12562.23 Placenta Clontech 31.16, 30.91 1280.82 1442.99 1361.91 5.26 9.51 112945.87 Prostate 33.5,33.11 420.13 506.76 463.45 13.00 16.67 17724.08 Rectum 34.48, 33.88 263.61 350.22 306.92 1.23 40.65 112476.22 Salivary Gland 34.48, 34.32 263.4 284.18 273.79 7.31 6.84 11872.71 Skeletal Muscle 40, 39.37 0 25.73 12.87 1.26 39.68 1510.52 Clontech Skin 35.52, 35.13 160.58 193.62 177.10 1.21 41.32 17318.18 Small Intestine 36.79, 36.59 87.74 96.5 92.12 0.98 51.07. 14704.80 Spleen 34.45, 34.51 267.45 260 263.73 4.92 10.16 12680.13 Stomach 35. -16, 33.89 191.03 348.48 1269.76 2.73 18.32 14940.57 Testis Clontech 38.19, 37.07 45.22 76.91 61.07 0.57 87.87 15365.99 Thymus Clontech 33.74, 33.57 374.59 406.79. 390.69 9.89 5.06 1975.18 Thyroid 34.18, 33.46 304.38 427.57 365. 98 2.77 18.05 6606.05 Trachea Clontech 32.67, 31.27 623.94 1213.65 918.80 9.71 5.15 4731.18 Urinary Bladder 32.07, 31.34 830.04 1176.15 1003.10 5.47 9.14 9169.06 Uterus 31.75, 31.37 968.5 1157.09 1062.80 15.34 9.36 9951.26 genomic 31.33 1181.44 b-actin 28.56 14411.32 1.OOE+05 122.12 1100000 22.12 100000 1.00E+04 26.72 10000 1.00E+04 26.91 10000 1.OOE+03 31.28 1000 1.00E+03 31.5 1000 1.OOE+02 36.35 100 1.00E+02 37.09 100 1.00E+01 40 L.OOE+01 40 1.00E-00 40 1 L.OOE-00 40 0 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies of Sample Fold sbg1O02620TIa number GOI mRNA Change (GSK copies detected/ in identifie 50 ng Disease r) total Populati _RNA on colon normal GW98-167 21941 24.54 22693.01 45386.02 colon normal colon tumor GW98-166 21940 24.18 26862.61 53725.22 colon tumor 1.18 colon normal GW98-178 22080 27.08 6895.34 13790.68 colon normal colon tumor GW98-177 22060 28.41 3692.19 7384.38 colon tumor -1.87 colon normal GW98-561 23514 26.58 8698.68 17397.36 colon normal colon tumor GW98-560 23513 27.85 4799.22 9598.44 colon tumor -1.81 colon normal GW98-894 24691 25.9 11972.57 23945.14 colon normal colon tumor GW98-893 24690 28.04 4396.4 8792.80 colon tumor -2.72 lung normal GW98-3 20742 24.25 26016.9 52033.80 lung normal lung tumor GW98-2 20741 27.64 5300.37 10600.74 lung tumor -4.91 lung normal GW97-179 20677 25.1 17476.66 34953.32 lung normal lung tumor GW97-178 20676 25.53 14274.54 28549.08 lung tumor -1.22 lung normal GW98-165 21922 24.62 21917.37 43834.74 lung normal lung tumor GW98-164 21921 25.64 13526.49 27052.98 lung tumor -1.62 lung normal GW98-282 22584 27.08 6884.03 13768.06 lung normal lung tumor GW98-281 22583 25.37 15385.8 30771.60 lung tumor 2.23 breast normal GWOO- 28750 26.07 11065.25 11065.25 breast normal 392 breast tumor GWOO-391 28746 26.87 7611.48 15222.96 breast tumor 1.38 breast normal GWOO- 28798 28.65 3294.68 3294.68 breast normal 413 breast tumor GWOO-412 28797 28.52 3496.94 6993.88 breast tumor 2.12 breast normal GWOO- 27592- 29.47 2243.69 2243.69 breast normal 235:238 breast tumor GWOO- 27588- 25.83 12385.23 12385.23 breast tumor 5.52 231:234 91 breast normal GW98- 23656 26.05 11188.07 22376.14 breast normal 621 breast tumor GW98-620 23655 26.03 11303.95 22607.90 breast tumor 1.01 brain normal BB99-542 25507 27.68 5198.79 10397.58 brain normal brain normal BB99-406 25509 29.81 1909.01 3818.02 brain normal brain normal BB99-904 25546 31.84 735.25 1470.50 brain normal brain stage 5 ALZ 25502 28.43 3650.66 7301.32 brain stage 5 ALZ 1.40 BB99-874 brain stage 5 ALZ 25503 29.01 2785.56 5571.12 brain stage 5 ALZ 1.07 BB99-887 brain stage 5 ALZ 25504 29.65 2059.62 4119.24 brain stage 5 ALZ -1.27 brain stage 5 ALZ 25542 30.01 1742.3 3484.60 brain stage 5 ALZ -1.50 CT lung KC normal 25.49 14553.17 29106.34 CT lung____ lung 26 KC normal 31.8 749.93 749.93 lung lung 27 KC normal 33.35 362.66 362.66 lung 27 lung 24 KC COPD 30.67 1275.68 1275.68 lung 24 -6.03 lung 28 KC COPD 29.25 2490.39 2490.39 lung 28 -3.09 lung 23 KC COPD 30.11 1661.24 1661.24 lung 23 -4.63 lung 25 KC normal. 32.45 553.75 553.75 lung asthmatic lung 29321 27.3 6215.19 6215.19 asthmatic lung -1.24 OD03112_______ asthmatic lung 29323 26.66 8407.3 16814.60 asthmatic lung 2.19 asthmatic lung 29322 24.06 28466.73 56933.46 asthmatic lung 7.40 OD03397 asthmatic lung 29325 26.22 10313.71 20627.42 asthmatic lung 2.68 endo cells KC control 40 0 0.00 endo cells endo VEGF KC 40 0 0.00 endo VEGF 0.00 endo bFGF KC 40 0 0.00 endo bFGF 0.00 heart Clontech normal 27.58 5449.78 10899.56 heart____ heart (T-1 ischemic 29417 28.42 3670.86 7341.72 heart T-1 -1.48 heart(T-14) non- 29422 27.18 6570.11 13140.22 heart T-14 1.21 obstructive DCM heart (T-3399) DCM 29426 26.23 10277.2 20554.40 heart T-3399 1.89 adenoid GW99-269 26162 31.98 688.86 1377.72 adenoid tonsil GW98-280 22582. 29.31 2421.67 4843.34 tonsil T cells PC00314 28453 29.53 2178.21 4356.42 T cells PBMNC 33.23 383.88 383.88 PBMNC monocyte 31.07 1057.9 2115.80 monocyte B cells PC00665 28455 35.97 106.01 212.02 B cells____ dendritic cells 28441 33.56 328.62 657.24 dendritic cells neutrophils 28440 22.32 64510.36 64510.36 neutrophils eosinophils 28446 24.18 26910.17 53820.34 eosinophils BM unstim 30.35 1480.07 1480.07 BM unstim BMstim 31.71 782.56 782.56 BMstim -1.89 osteo dif 31.42 895.71 895.71 osteo dif 2.03 osteo undif 32.93 440.66 440.66 osteo undif chondrocytes 28.98 2820.8 7052.00 chondrocytes OA Synovium IP12/01 29462 25.37 15383.84 15383.84 OA Synovium OA Synovium NP10/01 29461 27.12 6763.44 13526.88 OA Synovium OA Synovium NP57/00 28464 26.48 9130.81 18261.62 OA Synovium RA Synovium NP03/01 28466 27.78 4967.23 9934.46 RA Synovium RA Synovium NP71/00 28467 24.72 20923.66 41847.32 RA Synovium RA Synovium NP45/00 28475 26.15 10658.82 21317.64 RA Synovium OA bone (biobank) 29217 28.68 3248.19 3248.19 OA bone (biobank) OA bone Sample 1 J. Emory 27.19 6545.82 13091.64 OAbone OA bone Sample 2 J. Emory 27.24 6384.92 12769.84 OA bone Cartilage (pool) Normal 26.28 10016.65 20033.30 Cartilage (pool) Cartilage (pool) OA 26.67 8342.92 16685.84 Cartilage (pool) -1.20 PBL unifected 28441 31.05 1069.84 2139.68 PBL unifected PBL HIV B 28442 31.7 788.06 1576.12 PBL HIV IIB -1.36 uninfected 29158 26.37 9631.13 19262.26 MRC5 uninfected (100%) (100%) HSV strain F 29178 28.38 3747.38 7494.76 MRC5 HSV -2.57 strain F W12 cells 29179 35.15 155.25 310.50 W12 cells Keratinocytes 29180 34.93 172.87 345.74 Keratinocytes B-actin control 28.06 4342.74 genomic 30.54 1356.79 1.00E+05 21.39 100000 1.00E+05 21.64 100000 1.00E+04 26.21 10000 1.00E+04 26.24 10000 1.00E+03 30.9 1000 1.00E+03 30.97 1000 1.00E+02 36.34 100 1.00E+02 36.22 100 1.OOE+O 1 40 1.00E+01 40 0 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 Gene Name sbg1002620TIa Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.18 colon tumor -1.87 colon tumor -1.81 colon tumor -2.72 lung tumor -4.91 lung tumor -1.22 lung tumor -1.62 lung tumor 2.23 breast tumor 1.38 breast tumor 2.12 breast tumor 5.52 breast tumor 1.01 brain stage 5 ALZ 1.40 brain stage 5 ALZ 1.07 brain stage 5 ALZ -1.27 brain stage 5 ALZ -1.50 lung 24 -6.03 lung 28 -3.09 lung 23 -4.63 asthmatic lung -1.24 asthmatic lung 2.19 asthmatic lung 7.40 asthmatic lung 2.68 endo VEGF 0.00 endo bFGF 0.00 heart T-1 -1.48 heart T-14 1.21 heart T-3399 1.89 BM stim -1.89 osteo dif 2.03 Cartilage (pool) -1.20 PBL HIV IIB -1.36 HSV strain F -2.57 Gene Name sbgl002620TIb Moderate to high overall expression. Highest normal expression in whole brain, endometrium, jejunum, placenta, thymus, and urinary bladder. Highest disease expression in one of the colon normal/tumor pairs, one of the normal lung samples, one of the asthmatic lung samples, the neutrophils, and the eosinophils. Strong expression in all of the GI tract samples implicates this gene in IBS, IBD, and Crohn's disease. Downregulation in 1 of 4 lung tumor samples is sufficient to make a disease claim in cancer of the lung. Downregulation in 3 of 3 COPD lung samples suggests involvement in chronic obstructive pulmonary disease. Upregulation in 1 of 4 asthmatic lung samples implies a role in asthma. Upregulation in 2 of 3 heart samples suggests this gene may play a role in non-obstructive and obstructive dilated cardiac myopathy. High expression in the RA and OA synovium samples as well as high expression in the chondrocytes and T cells implicates this gene in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Averag 18S 50 copies of sbg1002620TIb 1 and 2) GOI GOI e GOI rRNA ng/18S mRNA copies copies Copies (ng) rRNA detected (sample (sample (ng) /50 ng 1) 2) total

RNA

Subcutaneous 31.35, 31.44 58.54 55.11 56.83 3.06 16.34 928.51 Adipocytes Zenbio Subcutaneous Adipose 35.12, 34.21 5 9.05 7.03 0.96 52.36 367.80 Zenbio Adrenal Gland Clontech 40, 34.29 0 8.61 4.31 0.61 81.97 352.87 Whole Brain Clontech 26.02, 26.06 1897.9 1849.19 1873.55 7.24 6.91 12938.85 Fetal Brain Clontech 40,36.43 0 2.13 1.07 0.48 103.95 110.71 Cerebellum Clontech 40, 36.05 0 2.74 1.37 2.17 23.04 31.57 Cervix 32.23, 33.04 33.11 19.47 26.29 2.42 20.66 543.18 Colon 30.44, 30.45 105.93 105.29 105.61 2.71 18.45 1948.52 Endometrium 30.86, 30.56 80.75 97.92 89.34 0.73 68.21 6093.79 Esophagus 33.03, 32.34 19.62 30.66 25.14 1.37 36.50 917.52 Heart Clontech 40, 35.05 0 5.26 2.63 1.32 37.88 99.62 Hypothalamus 40, 36.17 0 2.53 1.27 0.32 155.28 196.43 Ileum 31.25, 30.31 62.52 115.58 89.05 2.58 19.38 1725.78 Jejunum 27.75, 27.93 612.01 543.46 577.74 6.60 7.58 4376.78 Kidney 32.59, 31.86 26.03 42.14 34.09 2.12 23.58 803.89 Liver 34.66, 34.5 6.77 7.52 7.15 1.50 33.33 238.17 Fetal Liver Clontech 29.08, 28.58 256.83 356.67 306.75 10.40 4.81 1474.76 Lung 30.74, 30.68 87.44 90.91 89.18 2.57 19.46 1734.92 Mammary Gland 27.49, 26.81 725.02 1132.42 928.72 13.00 3.85 3572.00 Clontech Myometrium 31.2, 30.29 64.54 117.26 90.90 2.34 21.37 1942.31 Omentum 31.19, 30.12 65.05 130.86 97.96 3.94 12.69 1243.08 Ovary 30.24, 30.54 120.95 99.3 110.13 4.34 11.52 1268.72 Pancreas 36.01, 36.55 2.81 1.97 2.39 0.81 61.80 147.71 Head of Pancreas 33.95, 35.73 10.72 3.36 7.04 1.57 31.85 224.20 Parotid Gland 32.16, 33.16 34.51 18.05 26.28 5.48 9.12 239.78 Placenta Clontech 28.42, 28.02 395.01 512.77 453.89 5.26 9.51 4314.54 Prostate 30.61, 31.28 95.23 61.5 78.37 3.00 16.67 1306.08 Rectum 30.5, 30.93 101.73 76.9 89.32 1.23 40.65 3630.69 Salivary Gland 31.17, 31.07 65.95 70.23 68.09 7.31 6.84 465.73 Clontech Skeletal Muscle 40, 40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 34.37, 33.12 8.18 18.53 13.36 1.21 41.32 551.86 Small Intestine 36.71, 34.96 1.78 5.55 3.67 0.98 51.07 187.18 Clontech Spleen 30.54, 31.29 99.47 60.88 80.18 4.92 10.16 814.79 Stomach 32.4,31.53 29.49 52 40.75 2.73 18.32 746.25 Testis Clontech 34.4, 35.19 8.03 4.79 6.41 0.57 87.87 563.27 Thymus Clontech 27.18, 27.12 888.84 924.29 906.57 9.89 5.06 4583.24 Thyroid 32.17, 30.89 34.36 79.27 56.82 2.77 18.05 1025.54 Trachea Clontech 30.01, 29.25 140.31 230.28 185.30 9.71 5.15 954.15 Urinary Bladder 28.33, 27.87 420.47 565.71 493.09 5.47 9.14 4507.22 Uterus 29.09, 28.81 255.27 308 281.64 5.34 9.36 2637.03 genomic 27.16 900.78 b-actin 27.4 769.87 1.00E+05 19.87 100000 1.00E+05 19.95 100000 1.00E+04 23.4 10000 1.00E+04 23.39 100(0 1.OOE+03 26.94 1000 1.00E+03 26.95 1000 1.00E+02 31.02 100 1.00E+02 30.96 100 1.0012+01 33.46 10 l.OOE+01 40 0 1.OOE-00 40 0 1.OOE-00 40 NTC 40 NTC 40 0 Sample Reg Ct Mean copies of Sample Fold sbglO0262OTIb number GOI mRNA Chang (GSK copies detected e in identifier /50 ng Diseas )total e RNA Popula colon normal GW98-167 21941 22.85 18631.2 37262.40 colon normal colon tumor GW98-166 21940 22.51 23090.96 46181.92 colon tumor 1.24 colon normal GW98-178 22080 25.49 3620.45 7240.90 colon normal colon tumor GW98- 177 22060 26.88 1527.3 3054.60 1colon tumor -2.37 colon normal GW98-561 23514 25.37 3901.36 7802.72 colon normal colon tumor GW98-560 23513 26.08 2512.21 5024.42 colon tumor -1.55 colon normal GW98-894 24691 23.78 10441.49 20882.98 colon normal colon tumor GW98-893 24690 25.54 3515.48 7030.96 colon tumor -2.97 lung normal GW98-3 20742 22.6 21810.56 43621.12 lung normal lung tumor GW98-2 20741 26.19 2349.32 4698.64 lung tumor -9.28 lung normal GW97- 179 20677 23.38 13423.28 26846.56 lung normal lung tumor GW97- 178 20676 24.51 6653.03 13306.06 lung tumor -2.02 lung normal GW98-165 21922 23.68 11120.91 22241.82 lung normal lung tumor GW98-164 21921 24.37 7242.32 14484.64 lung tumor -1.54 lung normal GW98-282 22584 25.05 4745.83 9491.66 lung normal lung tumor GW98-28 1 22583 23.57 11943.28 23886.56 lung tumor 12.52 breast normal GWOO- 28750 24.84 5415.88 5415.88 breast normal 392 breast tumor GWOO-391 28746 24.98 4973.9 9947.80 breast tumor 1.84 breast normal GWOO- 28798 24.69 5954.77 5954.77 breast normal 413 breast tumor GWOO-412 28797 26.38 2081.99 4163.98 breast tumor -1.43 breast normal GWOO- 27592-95 25.04 4792.18 4792.18 ,breast normal 235:238 breast tumor GWOO- -27588-91 23.63 11520.86 11520.86 breast tumor 2.40 231:234 breast normal GW98- 23656 23.22 14836.24 129672.48 breast normal 621 breast tumor GW98-620 23655 24.24 7879 115758.00 1breast tumor -1.88 brain normal BB99-542 25507 25.16 4447.15 18894.30 1brain normal brain normal BB99-406 25509 27.05 1377.71 12755.42 1brain normal brain normal BB99-904 25546 29.35 330.53 661.06 brain normal brain stage 5 ALZ 25502 27.64 956.16 1912.32 brain stage 5 -2.15 BB99-874

ALZ

brain stage 5 ALZ 25503 127.02 1400.04 2800.08 brain stage 1.47 BB99-887 I ALZ brain stage 5 ALZ 25504 27.4 1105.21 2210.42 brain stage 5 -1.86 BB99-862

ALZ

brain stage 5 ALZ 25542 27.1 1336.02 2672.04 brain stage 5 -1.54 BB99-927

ALZ

CT lung KC normal 23.52 12295.29 24590.58 CT lung lung 26 KC normal 31.42 91.19 91.19 lung 26 lung 27 KC normal 32.34 51.71 51.71 lung 27 lung 24 KC COPD 31.27 100.29 100.29 lung 24 -61.80 lung 28 KC COPD 28.64 511.37 511.37 lung 28 -12.12 lung 23 KC COPD 30.52 159.17 159.17 lung 23 -38.94 lung 25 KC normal 32.15 57.91 57.91 lung asthmatic lung 29321 23.19 15086.65 15086.65 asthmatic lung 2.43 OD03112 asthmatic lung 29323 24.76 5706.9 11413.80 asthmatic lung 1.84 OD03433 asthmatic lung 29322 21.71 37760.01 75520.02 asthmatic lung 12.18 OD03397 asthmatic lung 29325 24.16 8255.16 16510.32 asthmatic lung 2.66 OD04928 endo cells KC control 37.31 2.36 2.36 endo cells endo VEGF KC 40 0 0.00 endo VEGF -2.36 endo bFGF KC 35.67 6.54 6.54 endo bFGF 2.77 heart Clontech normal 26.32 2170.24 4340.48 heart heart T-1 ischemic 29417 25.87 2863.04 5726.08 heart T-1 1.32 heart (T-14) non- 29422 24.62 6200.03 12400.06 heart T-14 2.86 obstructive DCM heart (T-3399) DCM 29426 24.06 8775.18 17550.36 heart T-3399 4.04 adenoid GW99-269 26162 29.2 362.88 725.76 adenoid tonsil GW98-280 22582 27.24 1222.33 2444.66 tonsil T cells PC00314 28453 28.09 723.06 1446.12 T cells PBMNC 30.67 145.75 145.75 PBMNC monocyte 28.42 587.16 1174.32 monocyte B cells PC00665 28455 34.17 16.57 33.14 B cells dendritic cells 28441 31.78 72.95 145.90 dendritic cells neutrophils 28440 21.46 44297.23 44297.23 neutrophils eosinophils 28446 22.79 19332.21 38664.42 eosinophils BM unstim 29.22 358.53 358.53 BM unstim BM stim 31.27 100.39 100.39 BM stim -3.57 osteo dif 30.14 202.25 202.25 osteo dif 4.97 osteo undif 32.72 40.67 40.67 osteo undif chondrocytes 27.3 1178.3 2945.75 chondrocytes OA Synovium IP12101 29462 23.33 13860.23 13860.23 OA Synovium OA Synovium NP10/01 29461 25.3 4080.49 8160.98 OA Synovium OA Synovium NP57/00 28464 25.23 4253.8 8507.60 OA Synovium RA Synovium NP03/01 28466 25.46 3686.62 7373.24 RA Synovium RA Synovium NP71/00 28467 23.31 14036.44 28072.88 RA Synovium RA Synovium NP45/00 28475 24.28 7658.52 15317.04 RA Synovium OA bone (biobank) 29217 26.48 1958.1 1958.10 OA bone (biobank) OA bone Sample 1 J. Emory 25.28 4131.76 8263.52 OA bone OA bone Sample 2 J. Emory 25.23 4242.9 8485.80 OA bone Cartilage (pool) Normal 24.05 8829.67 17659.34 Cartilage (pool) Cartilage (pool) OA 24.28 7685.44 15370.88 Cartilage (pool) -1.15 PBL unifected 28441 29.33 334.71 669.42 PBL unifected PBL HIV IIIB 28442 29.59 283.96 567.92 PBL IV IIIB -1.18 uninfected 29158 23.92 9595.12 19190.24 (100%) uninfected (100%) HSV strain F 29178 25.2 4341.36 8682.72 MRC5 HSV -2.21 strain F W12 cells 29179 30.43 168.9 337.80 W12 cells Keratinocytes 29180 29.66 272.9 545.80 Keratinocytes B-actin control 27.64 956.41 genomic 27.35 1143.39 1.00E+05 20.14 100000 1.OOE+05 20.26 100000 1.00E+04 23.6 10000 1.00E+04 24.02 10000 1.00E+03 27.49 1000 1.00E+03 27.5 1000 1.00E+02 31.66 100 1.00E+02 '1.01 100 1.00E+01 40 0 1.00E+01 40 0 1.00E-00 40 0 1.OOE-00 40 0 NTC 40 0 Gene Name sbgl002620TIb Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.24 colon tumor -2.37 colon tumor -1.55 colon tumor -2.97 lung tumor -9.28 lung tumor -2.02 lung tumor -1.54 lung tumor 2.52 breast tumor 1.84 breast tumor -1.43 breast tumor 2.40 breast tumor -1.88 brain stage 5 ALZ -2.15 brain stage 5 ALZ -1.47 brain stage 5 ALZ -1.86 brain stage 5 ALZ -1.54 lung 24 -61.80 lung 28 -12.12

I

lung 23 -38.94 asthmatic lung 2.43 asthmatic lung 1.84 asthmatic lung 12.18 asthmatic lung 2.66 endo VEGF -2.36 endo bFGF 2.77 heart T-1 1.32 heart T-14 2.86 heart T-3399 4.04 BM stim -3.57 osteo dif 4.97 Cartilage (pool) -1.15 PBL HIV IIIB -1.18 HSV strain F -2.21 Gene Name sbg102200MCTa Moderate to low overall expression. Highest normal expression in the subcutaneous adipose tissue, whole brain, fetal brain, cerebellum, and fetal liver. Highest disease expression in 2 of 4 lung tumor samples, one of the normal lung samples, one of the normal breast samples, and the CT lung sample.

Downregulation in 1 of 4 breast cancer samples implicates this gene in cancer of the breast.

Downregulation in 3 of 3 COPD lung samples suggests involvement in chronic obstructive pulmonary disease. Moderate expression in the OA and RA synovium as well as the PBLs, adenoid, tonsil, T cells, B cells, and the chondrocytes indicates involvement in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg102200MCTa 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 36.01, 34.76 3.83 8.04 5.94 3.06 16.34 96.98 Adipocytes Zenbio Subcutaneous Adipose 34.85, 33.96 7.63 12.94 10.29 0.96 52.36 538.48 Zenbio Adrenal Gland Clontech 40, 40 0 0 0.00 0.61 81.97 0.00 Whole Brain Clontech 26.05, 26.18 1434.25 1331.2 1382.73 7.24 6.91 9549.21 Fetal Brain Clontech 40, 34.46 0 9.63 4.82 0.48 103.95 500.52 Cerebellum Clontech 31.7,32.73 49.65 26.9 38.28 2.17 23.04 881.91 Cervix 40, 40 0 0 0.00 2.42 20.66 0.00 Colon 38.55, 38.57 0.84 0.83 0.84 2.71 18.45 15.41 Endometrium 40, 40 0 0 0.00 0.73 68.21 0.00 Esophagus 35.23, 40 6.09 0 3.05 1.37 36.50 111.13 Heart Clontech 40, 40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 39.8,40 0.4 0 0.20 0.32 155.28 31.06 Ileum 34.16, 40 11.53 0 5.77 2.58 19.38 111.72 Jejunum 32.82, 33.18 25.46 20.6 23.03 6.60 7.58 174.47 Kidney 34.23,34.1 11.02 11.9 11.46 2.12 23.58 270.28 Liver 35.35, 37.28 5.65 1.79 3.72 1.50 33.33 124.00 Fetal Liver Clontech 29.45, 28.98 189.89 250.96 220.43 10.40 4.81 1059.74 Lung 34.99, 33.43 7.04 17.81 112.43 2.57 19.46 241.73 Mammary Gland 31.76, 31.05 48.02 73.18 60.60 13.00 3.85 233.08 Clontech Myometrium 34.46, 35.22 9.64 6.12 7.88 2.34 21.37 168.38 Omentum 37.94, 34.13 1.21 11.71 6.46 3.94 12.69 81.98 Ovary 34.03, 33.43 12.44 17.77 15.11 4.34 11.52 174.02 Pancreas 40,40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40, 40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 32.56, 31.81 29.88 46.65 38.27 5.48 9.12 349.13 Placenta Clontech 40, 40 0 0 0.00 5.26 9.51 0.00 Prostate 40,36.21 0 3.39 1.70 3.00 16.67 28.25 Rectum 40,39.37 0 0.52 0.26 1.23 40.65 10.57 Salivary Gland 30.6,31.77 95.89 47.76 71.83 7.31 6.84 491.28 Clontech Skeletal Muscle 40,40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 34.47, 35.32 9.58 5.75 7.67 1.21 41.32 316.74 Small Intestine 40, 40 0 0 0.00 0.98 51.07 0.00 Clontech Spleen 34.1,36.49 11.93 2.87 7.40 4.92 10.16 75.20 Stomach 35.17, 36.07 6.3 3.68 4.99 2.73 18.32 91.39 Testis Clontech 37.98,40 1.19 0 0.60 0.57 87.87 52.28 Thymus Clontech 31.28,30.4 63.69 108.05 85.87 9.89 5.06 434.13 Thyroid 33.08, 32.96 21.88 23.47 22.68 2.77 18.05 409.30 TracheaClontech 32.54,31.34 30.14 61.71 45.93 9.71 5.15 236.48 Urinary Bladder 33.91, 40 13.32 0 6.66 5.47 9.14 60.88 Uterus 33.71, 32.43 15.04 32.13 23.59 5.34 9.36 220.83 genomic 26.3 1237.42 b-actin 27.49 610.72 1.00E+05 19.18 100000 1.00E+05 19.45 100000 1.00E+04 22.6 10000 1.00E+04 22.53 10000 1.00E+03 26.17 1.00E+03 26.19 1.00E+02 30.61 100 1.00E+02 30.53 100 1.00E+01 40 1.00E+01 34.91 1.00E-00 40 0 1.00E-00 40 0 NTC 40 NTC 40 0 |0 ~ng n total colon normal GW98-167 21941 28.58 519.72 1039.44 colon normal colon tumor GW98-166 21940 30.18 202.86 1405.72 colon tumor -2.56 colon normal GW98-178 22080 31.39 100.15 1200.30 colon normal colon tumor GW98-177 22060 29.62 282.42 1564.84 colon tumor 2.82 colon normal GW98-561 23514 30.36 183.13 366.26 colon normal colon tumor GW98-560 23513 30.45 173.87 347.74 colon tumor -1.05 colon normal GW98-894 24691 30.23 196.98 393.96 colon normal colon tumor GW98-893 24690 30.35 183.76 367.52 colon tumor -1.07 lung normal GW98-3 20742 26.68 1575.72 13151.44 lung normal lung tumor GW98-2 20741 28.8 456.47 912.94 lung tumor -3.45 lung normal GW97- 179 20677 27.94 754.47 1508.94 lung normal lung tumor GW97- 178 20676 26.27 2002.28 4004.56 lung tumor 2.65 lung normal GW98-165 21922 26.87 1411.09 2822.18 lung normal lung tumor GW98-164 21921 29.38 325.51 1651.02 lung tumor -4.34 lung normal GW98-282 22584 30 225.32 450.64 lung normal lung tumor GW98-281 22583 28.64 502.02 1004.04 lung tumor 2.23 breast normal GWOO-392 .28750 28.32 602.59 602.59 breast normal breast tumor GWOO-391 28746 28.05 709.37 1418.74 breast tumor 2.35 breast normal GWOO-4 13 28798 29.56 292.43 1292.43 breast normal breast tumor GWOO-412 28797 30.05 218.89 437.78 breast tumor 1.50 breast normal GWOO.. 27592-95 30.96 128.91 128.91 breast normal 235:23 8 breast tumor GW00- 27588-91 30.57 161.3 161.30 breast tumor 1.25 231:234 breast normal GW98-621 23656 27.04 1275.81 2551.62 breast normal breast tumor GW98-620 23655 31.35 102.26 204.52 breast tumor -12.48 brain normal BB99-542 25507 28.44 564.32 1128.64 brain normal brain normal BB99-406 25509 29.01 402.37 804.74 brain normal brain normal BB99-904 25546 29.67 274.03 1548.06 brain normal brain stage 5 ALZ BB99- 25502 29.6 284.82 1569.64 brain stage 5 ALZ -1.45 874 brain stage 5 ALZ BB99- 25503 27.92 765.16 11530.32 brain stageS5 ALZ 1.85 887 brain stage 5 ALZ BB99- 25504 28.74 472.27 1944.54 brain stage 5 ALZ 1.14 brain stage 5 ALZ BB99- 25542 29.3 340.25 680.50 brain stage 5 ALZ -1.22 CT lung KC normal 26.69 1569.87 3139.74 CT lung lung 26 KC normal 31.07 120.9 120.90 lung 26 lung 27 KC normal 31.17 113.69 113.69 lung lung 24 KG COPD 31.8 78.78 78.78 lung 24 -10.98 lung 28 KC CQPD 32.79 44.02 44.02 lung 28 -19.65 lung 23 KC COPD 31.35 102.33 102.33 lung 23 -8.45 lung 25 KG normal 31.66 85.57 185.57 lung asthimatic lungr OD03112 29321 28.76 467.45 467.45 asthmatic lung -1.85 asthmatic lung 0D03433 29323 27.73 851.21 1702.42 asthmatic lung 1.97 asthmatic lung 0D03397 29322 27.81 812.68 1625.36 asthmatic lung 1.88

I

asthmatic lung OD04928 29325 29.42 317.12 634.24 asthmatic lung -1.36 endo cells KC control 33.06 37.57 37.57 endo cells endo VEGF KC 33.9 22.97 22.97 endo VEGF -1.64 endo bFGF KC 33.13 36.03 36.03 endo bFGF -1.04 heart Clontech normal 31.1 118.18 236.36 heart heart (T-1 ischemic 29417 31.16 114.67 229.34 heart T-1 -1.03 heart (T-14) non- 29422 30.52 166.47 332.94 heart T-14 1.41 obstructive DCM heart (T-3399) DCM 29426 30.14 208.3 416.60 heart T-3399 1.76 adenoid GW99-269 26162 29.07 388.9 777.80 adenoid tonsil GW98-280 22582 28.29 614.82 1229.64 tonsil T cells PC00314 28453 29.78 256.1 512.20 T cells PBMNC 33.73 25.44 25.44 PBMNC monocyte 33.52 28.71 57.42 monocyte B cells PC00665 28455 28.66 495.36 990.72 B cells dendritic cells 28441 30.81 140.17 280.34 dendritic cells neutrophils 28440 30.17 204.92 204.92 neutrophils eosinophils 28446 34.19 19.39 38.78 eosinophils BM unstim 35.9 7.11 7.11 BM unstim BM stim 35.77 7.7 7.70 BM stim 1.08 osteo dif 34.98 12.18 12.18 osteo dif 2.55 osteo undif 36.59 4.77 4.77 osteo undif chondrocytes 32.91 41.03 102.58 chondrocytes OA Synovium IP12/01 29462 29.16 370.33 370.33 OA Synovium OA Synovium NP10/01 29461 30.69 151.13 302.26 OA Synovium OA Synovium NP57/00 28464 29.51 301.55 603.10 OA Synovium RA Synovium NP03/01 28466 30.36 183.35 366.70 RA Synovium RA Synovium NP71/00 28467 29.27 346.61 693.22 RA Synovium RA Synovium NP45/00 28475 29.13 376.88 753.76 RA Synovium OA bone (biobank) 29217 30.47 171.6 171.60 OA bone (biobank) OA bone Sample 1 J. Emory 30.05 219.19 438.38 OA bone OA bone Sample 2 J. Emory 31.13 116.62 233.24 OA bone Cartilage (pool) Normal 30.65 154.56 309.12 Cartilage (pool) Cartilage (pool) OA 32.01 69.39 138.78 Cartilage (pool) -2.23 PBL unifected 28441 27.91 769.91 1539.82 PBL unifected PBLHIV IIB 28442 28.14 672.12 1344.24 PBLHIVIIIB -1.15 MRCS uninfected 29158 31.66 85.38 170.76 MRC5 uninfected (100%) (100%) HSV strain F 29178 30.08 214.88 429.76 MRC5 HSV strain 2.52

F

W12 cells 29179 33.33 32.15 64.30 W12 cells Keratinocytes 29180 30.64 155.16 310.32 Keratinocytes B-actin control 27.55 946.64 genomic 26.82 1451.22 1.00E+05 19.71 100000 1.00E+05 19.95 100000 1.00E+04 23.43 10000 1.00E+04 23.38 10000 l.00E+03 26.88 100 1.OOE+03 26.8 1000 1.OOE+02 31.99 100 1.OOE-s02 32.15 100 1.00E+01 34.99 10 l.00E+O1 40 0 1.OOE-00 40 0 1.OQE-00 0b___ NTC 1___40 0 Gene Name sbglO2200MCra Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -2.56 colon tumor 2.82 colon tumor -1.05 colon tumor -1.07 lung tumor -3.45 lung tumor 2.65 lung tumor -4.34 lung tumor 2.23 breast tumor 2.35 breast tumor 1.50 breast tumor .1.25 breast tumor 12.48 brain stage 5 ALZ -1.45 brain stage 5ALZ 1.85 brain stage 5 ALZ 1.14 brain stage 5 ALZ -1.22 lung 24 -10.98 lung 28 -19.65 lung 23 -8.45 asthmatic lung -1.85 asthmatic lung 1.97 asthmatic lung 1.88 asthmatic lung -1.36 endoVEGF-1.64 -1.04 heartT- 1-1.03 heart 1.41 heart T-3399 1.76 BM Stim1.08 osteo dif 2.55 Cartilage (pool) -2.23 PBL FfV IIB -1.15 HSV strain F 2.52 Gene Name sbglO2200MCTh High to moderate overall expression. Highest normal expression in the whole brain, liver, fetal liver, and thymus. Highest disease expression in one of the colon normal/tumor pairs, one of the lung normal/tumor pairs, one of the asthmatic lung samples, the dendritic cells, and the uninfected and HIV-infected PBL cells. Upregulation in 2 of 4 breast tumor samples is sufficient to make a disease claim in cancer of the breast. Upregulation in 1 of 4 AD brain samples indicates a potential role in Alzheimer's disease. Downregulation in 3 of 3 COPD lung samples suggests involvement in chronic obstructive pulmonary disease. Upregulation in I of 4 asthmatic lung samples indicates a potential role for this gene in lung cancer. High expression in all of the immune cells. Also high to moderate expression in the OA and RA synovium samples, the OA bone samples, and in the chondrocytes suggests an involvement in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg102200MCTh 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 35.66, 34.05 3.76 10.2 6.98 3.06 16.34 114.05 Adipocytes Zenbio Subcutaneous Adipose 40, 36 0.17 3.07 1.62 0.96 52.36 84.82 Zenbio Adrenal Gland Clontech 40, 40 0 0 0.00 0.61 81.97 0.00 Whole Brain Clontech 26.32, 26.41 1192.66 1124.69 1158.68 7.24 6.91 8001.90 Fetal Brain Clontech 40, 35.84 0 3.38 1.69 0.48 103.95 175.68 Cerebellum Clontech 34.51, 34.28 7.68 8.8 8.24 2.17 23.04 189.86 Cervix 40, 34.34 3.17 8.5 5.84 2.42 20.66 120.56 Colon 33.67, 35.6 12.86 3.91 8.39 2.71 18.45 154.70 Endometrium 35.32,34.43 4.66 8.05 6.36 0.73 68.21 433.49 Esophagus 34.27,35.14 8.86 5.19 7.03 1.37 36.50 256.39 Heart Clontech 40,35.05 0 5.5 2.75 1.32 37.88 104.17 Hypothalamus 40,40 0 0 0.00 0.32 155.28 0.00 Ileum 35.29, 33.68 4.74 12.8 8.77 2.58 19.38 169.96 Jejunum 31.23, 30.98 57.65 67.22 62.44 6.60 7.58 472.99 Kidney 34.67, 34.21 6.95 9.2 8.08 2.12 23.58 190.45 Liver 30.76, 30.65 77.12 82.56 79.84 1.50 33.33 2661.33 Fetal Liver Clontech 26.8, 27.1 885.14 734.31 809.73 10.40 4.81 3892.91 Lung 40, 40 0 0.17 0.09 2.57 19.46 1.65 Mammary Gland 31.28, 31.37 56.1 52.95 54.53 13.00 3.85 209.71 Clontech Myometrium 34.16, 36.28 9.48 2.57 6.03 2.34 21.37 128.74 Omentum 34.18, 33.42 9.38 15 12.19 3.94 12.69 154.70 Ovary 34.21, 34.18 9.24 9.39 9.32 4.34 11.52 107.32 Pancreas 40, 40 0 0.14 0.07 0.81 61.80 4.33 Head of Pancreas 40,35.02 0 5.59 2.80 1.57 31.85 89.01 Parotid Gland 31.23, 31.9 57.68 38.33 48.01 5.48 9.12 438.00 Placenta Clontech 31.77, 33.13 41.33 17.94 29.64 5.26 9.51 281.70 Prostate 39.72, 35.03 0.31 5.56 2.94 3.00 16.67 48.92 Rectum 35.36, 34.34 4.53 8.5 6.52 1.23 40.65 264.84 Salivary Gland 30.52, 30.54 89.5 88.43 88.97 7.31 6.84 608.52 Clontech I Skeletal Muscle 40, 40 0 0 0.00 1.26 39.68 0.00 Clontech Skin 40, 40 0 0 0.00 1.21 41.32 0.00 Small Intestine 40, 39.27 0 0.41 0.21 0.98 51.07 10.47 Clontech Spleen 34.21, 33.54 9.2 13.91 11.56 4.92 10.16 117.43 Stomach 35.05, 33.62 5.51 13.22 9.37 2.73 18.32 171.52 Testis Clontech 40, 40 0 0 0.00 0.57 87.87 0.00 Thymus Clontech 28.56, 28.44 299.45 322.02 310.74 9.89 5.06 1570.96 Thyroid 31.65, 32.3 44.76 29.81 37.29 2.77 18.05 673.01 Trachea Clontech 32.3, 31.9 29.9 38.28 34.09 9.71 5.15 175.54 Urinary Bladder 34.34, 35.02 8.49 5.59 7.04 5.47 9.14 64.35 Uterus 33.07, 34.56 18.62 7.45 13.04 5.34 9.36 122.05 genomic 25.84 1597.08 b-actin 27.32 643.56 1.00E+05 19.22 100000 1.00E+05 19.33 100000 1.00E+04 22.48 10000 1.00E+04 22.95 10000 1.OOE+03 26.19 1000 1.00E+03 26.37 1000 1.00E+02 31.23 100 1.OOE+02 30.48 100 1.OOE+01 32.76 1.00E+01 35.02 1.OOE-00 40 0 1.OOE-00 40 0 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies of Sample Fold sbglO2200MCTh number GOI mRNA Change (GSK copies detected in identifie 150 ng Disease r) total Populati RNA on colon normal GW98-167 21941 26.48 1723.59 3447.18 colon normal colon tumor GW98-166 21940 26.06 2195.04 4390.08 colon tumor 1.27 colon normal GW98-178 22080 29.03 389.88 779.76 colon normal colon tumor GW98-177 22060 27.39 1015.65 2031.30 colon tumor 2.61 colon normal GW98-561 23514 26.74 1478.76 2957.52 colon normal colon tumor GW98-560 23513 q26.37 1831.8 3663.60 colon tumor 1.24 colon normal GW98-894 24691 25.58 2918.02 5836.04 colon normal colon tumor GW98-893 24690 25 4089.75 8179.50 colon tumor 1.40 lung normal GW98-3 20742 24.59 5183.31 10366.62 lung normal lung tumor GW98-2 20741 24.94 4232.23 8464.46 lung tumor -1.22 lung normal GW97-179 20677 25.73 2672.73 5345.46 lung normal lung tumor GW97-178 20676 25.36 3307.37 6614.74 lung tumor 1.24 lung normal GW98-165 21922 26.13 2109.28 4218.56 lung normal lung tumor GW98-164 21921 25.54 2973.82 5947.64 lung tumor 1.41 lung normal GW98-282 22584 27.08 1212.64 2425.28 lung normal lung tumor GW98-281 22583 27.45 979.82 1959.64 lung tumor -1.24 breast normal GWOO-392 28750 26.68 1536.57 1536.57 breast normal breast tumor GWOO-391 28746 26.58 1626.58 3253.16 breast tumor 2.12 breast normal GWOO-413 28798 31.71 81.9 81.90 breast normal breast tumor GWOO-412 28797 26.57 1632 3264.00 breast tumor 39.85 breast normal GWO0- 27592- 32.52 51.1 51.10 breast normal 235:238 breast tumor GWOO- 27588- 29.67 268.7 268.70 breast tumor 5.26 231:234 91 breast normal GW98-621 23656 26.48 1727.44 3454.88 breast normal breast tumor GW98-620 23655 25.65 2793.6 5587.20 breast tumor 1.62 brain normal BB99-542 25507 28.62 494 988.00 brain normal brain normal BB9-Q406 25509 29.45 304.68 609.36 brain normal brain normal BB 904 25546 30.08 211.25 422.50 brain normal brain stage 5 ALZ BB99- 25502 28.75 458.64 917.28 brain stage 5 ALZ 1.36 874 brain stage 5 ALZ BB99- 25503 26.86 1383.71 2767.42 brain stage 5 ALZ 4.11 887 brain stage 5 ALZ BB99- 25504 28.02 702.59 1405.18 brain stage 5 ALZ 2.09 862 brain stage5 ALZ BB99- 25542 29.57 284.31 568.62 brain stage 5 ALZ -1.18 927 1 CT lung KC normal 26.58 1624.29 3248.58 CT lung lung 26 KC normal 34.19 19.27 19.27 lung 26 lung 27 KC normal 32.45 53.23 53.23 lung 27 lung 24 KC COPD 33 38.6 38.60 lung 24 -21.75 lung 28 KC COPD 32.24 59.95 59.95 lung 28 -14.01 lung 23 KC COPD 32.87 41.63 41.63 lung 23 -20.17 lung 25 KC normal 33.04 37.52 37.52 lung asthmatic lung OD03112 29321 30.13 205.46 205.46 asthmatic lung -4.09 asthmatic lung OD03433 29323 27.82 788.82 1577.64 asthmatic lung 1.88 asthmatic lung OD03397 29322 25.17 3695.43 7390.86 asthmatic lung 8.80 asthmatic lung OD04928 29325 27.6 894.3 1788.60 asthmatic lung 2.13 endo cells KC control 28.2 633.43 633.43 endo cells endo VEGF KC 28.86 429.51 429.51 endo VEGF -1.47 endo bFGF KC 28.97 403.08 403.08 endo bFGF -1.57 heart Clontech normal 28.83 437.62 875.24 heart heart T- 1 ischemic 29417 28.42 557.54 1115.08 heart T- 1 1.27 heart (T-14) non- 29422 27.72 835.11 1670.22 heartT-14 1.91 obstructive

DCM

heart (T-3399) DCM 29426 28.63 493.01 986.02 heart T-3399 1.13 adenoid GW99-269 26162 27 1269.75 2539.50 adenoid tonsil GW98-280 22582 26.33 1876.29 3752.58 tonsil T cells PC00314 28453 29.15 363,35 726.70 T cells PBMNC 33.05 37.41 37.41 PBMNC monocyte 31.49 92.84 185.68 monocyte B cells PC00665 28455 26.5 1700.87 3401.74 B cells dendritic cells 28441 124.2 6511.17 13022.34 dendritic cells neutrophils 28440 27.01 1262.74 1262.74 neutrophils eosinophils 28446 29.23 347.08 694.16 eosinophils BM unstim 30.85 135.01 135.01 BM unstim BM stim 28.68 478.5 478.50 BM stim 3.54 osteo dif 31.03 121.2. 121.20 osteo dif 3.93 osteo undif 33.38 30.85 30.85 osteo undif chondrocytes 26.63 1579.73 3949.33 chondrocytes OA Synovium 1P12/01 29462 29.11 371.98 371.98 OA Synovium OA Synovium NP10/01 29461 29.45 304.55 609.10 OA Synovium OA Synovium NP57/00 28464 27.83 784.87 1569.74 OA Synovium RA Synovium NP03/01 28466 27.31 1063.77 2127.54 RA Synovium RA Synovium NP71/00 28467 27.08 1217.21 2434.42 RA Synovium RA Synovium NP45/00 28475 26.6 1606.41 3212.82 RA Synovium OA bone (biobank) 29217 28.65 485.63 485.63 OA bone (biobank) OA bone Sample 1 J. Emory 28.78 451.74 903.48 OA bone OA bone Sample 2 J. Emory 28.27 607.15 1214.30 OA bone Cartilage (pool) Normal 29.42 310.76 621.52 Cartilage (pool) Cartilage (pool) OA 30.09 209.7 419.40 Cartilage (pool) -1.48 PBL unifected 28441 23.85 7997.03 15994.06 PBL unifected PBL HIV IIIB 28442 24.85 4447.34 8894.68 PBL HIV IIIB -1.80 uninfected (100%) 29158 27.02 1258.46 2516.92 MRCS uninfected (100%) HSV strain F 29178 29.6 278.84 557.68 MRC5 HSV strain F -4.51 W12 cells 29179 27.21 1122.77 2245.54 W12cells Keratinocytes 29180 25.64 2815.12 5630.24 Keratinocytes B-actin control 27.78 807.72 genomic 27.04 1246.22 1.00E+05 19.69 100000 1.00E+05 20.01 100000 1.00E+04 23.15 10000 1.00E+04 23.2 10000 1.00E+03 27.02 1000 1.00E+03 26.76 1000 1.00E+02 31.45 100 1.00E+02 32.39 100 1.00E+01 35.72 1.00E+01 34.74 1.00E-00 40 0 1.00E-00 40 0 NTC 40 0 Gene Name sbgO102200MCTb Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 1.27 colon tumor 2.61 colon tumor 1.24 colon tumor 1.40 lung tumor -1.22 lung tumor 1.24 lung tumor 1.41 lung tumor -1.24 breast tumor 2.12 breast tumor 39.85 breast tumor 5.26 breast tumor 1.62 brain stage 5 ALZ 1.36 brain stage 5 ALZ 4.11 brain stage 5 ALZ 2.09 brain stage 5 ALZ -1.18 lung 24 -21.75 lung 28 -14.01 lung 23 -20.17 asthmatic lung -4.09 asthmatic lung 1.88 asthmatic lung 8.80 asthmatic lung 2.13 endo VEGF -1.47 endo bFGF -1.57 heart T-l1 1.27 heart T-14 1.91 heart T-3399 1.13 BM stim 3.54 osteo dif 3.93 Cartilage (pool) -1.48 PBL HIV IIIB -1.80 HSV strain F -4.51 Gene Name sbgl020380LYG Failed Gene Name sbgl007026SGLT Good to moderate overall expression. The highest normal expression is seen in the whole brain, cerebellum, hypothalamus, jejunum, fetal liver, rectum, and uterus. This gene shows system specific expression in samples representing the central nervous system, the female reproductive organs, and the GI tract. The expression seen in the disease samples confirms that seen in the normal samples with the highest levels of expression seen in the normal and Alzheimer's brain samples.

Upregulation in 1 of 4 colon tumor samples and 2 of 4 breast tumor samples as well as downregulation in 1 of 4 lung tumors poses a potential role for this gene in cancers of the colon and breast Downregulation in 2 of 4 Alzheimer's brain samples implies involvement in Alzheimer's disease. Downregulation in 3 of 3 COPD samples and upregulation in 2 of 4 asthmatic lung samples suggests a potential role for this gene in chronic obstructive pulmonary disorder. Upregulation in the VEGF-treated endothelial cell line implicates a possible role for this gene in angiogenesis.

Downregulated in the stimulated bone marrow sample. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in the T cells, B cells, neutrophils, and eosinophils implicates this gene in osteoarthritis and rheumatoid arthritis.

Sample sbg1007026SGLT Ct (sample Mean Mean Average 18S 50 copies of land 2) [GOI IGOI GOI rRNA ng/18 mRNA copies copies Copies (ng) S detected/ (sample (sample rRNA 50 ng 1) 2) (ng) total

RNA

Subcutaneous 40, 40 0 0 0.00 3.06 16.34 0.00 Adipocytes Zenbio II Subcutaneous Adipose 40, 40 0 0.1 0.05 0.96 52.36 2.62 Zenbio I Adrenal Gland Clontech 40, 38.76 0 0.31 0.16 0.61 81.97 12.70 Whole Brain Clontech 23.01, 22.63 3438.45 4301.69 3870.07 7.24 6.91 26727.00 Fetal Brain Clontech 35.91, 39.16 1.66 0.24 0.95 0.48 103.95 98.75 Cerebellum Clontech 34.55, 32.7 3.71 11.08 7.40 2.17 23.04 170.39 Cervix 34.21, 34.61 4.54 3.58 4.06 2.42 20.66 83.88 Colon 33.44, 33.7 7.16 6.14 6.65 2.71 18.45 122.69 Endometrium 34.88, 40 3.05 0.1 1.58 0.73 68.21 107.44 Esophagus 40, 40 0 0.1 0.05 1.37 36.50 1.82 Heart Clontech 39.63, 39.53 0.18 0.19 0.19 1.32 37.88 7.01 Hypothalamus 40, 35.34 0 2.33 1.17 0.32 155.28 180.90 Ileum 40, 40 0 0 0.00 2.58 19.38 0.00 Jejunum 30.1, 30.34 51.59 44.92 48.26 6.60 7.58 365.57 Kidney 33.49, 40 6.96 0 3.48 2.12 23.58 82.08 Liver 40, 33.7 0 6.15 3.08 1.50 33.33 102.50 Fetal Liver Clontech 29.58, 29.41 70.26 77.58 73.92 10.40 4.81 355.38 Lung 35.61, 37.83 1.98 0.53 1.26 2.57 19.46 24.42 Mammary Gland 33.05, 34.04 9.02 5.03 7.03 13.00 3.85 27.02 Clontech Myometriumn 33.63, 34.13 6.38 4.77 5.58 2.34 21.37 119.12 Omentum 40, 40 0 0 0.00 3.94 12.69 0.00 Ovary 35.38, 37.6 2.27 0.61 1.44 4.34 11.52 16.59 Pancreas 40, 37.1 0 0.82 0.41 0.81 61.80 25.34 Head of Pancreas 35.45, 36.72 2.18 1.03 1.61 1.57 31.85 51.11 Parotid Gland 36.88, 40 0.94 0 0.47 5.48 9.12 14.29 Placenta Clontech 33.84, 38.46 5.66 0.37 3.02 5.26 9.51 28.66 Prostate 38.76, 37.12 0.31 0.81 0.56 3.00 16.67 9.33 Rectum 36.18, 33.82 1.42 5.7 3.56 1.23 40.65 144.72 Salivary Gland Clontech 38.36, 39.93 0.39 0.12 0.26 7.31 6.84 1.74 Skeletal Muscle 35.69, 36.23 1.9 1.38 1.64 1.26 39.68 65.08 Clontech Skin 39.51, 40 0.2 0.09 0.15 1.21. 41.32 5.99 Small Intestine Clontech 40, 36.04 0.1 1.53 0.82 0.98 51.07 41.62 Spleen 33.51, 38.51 6.87 0.36 3.62 4.92 10.16 36.74 Stomach 34.14, 34.19 4.73 4.59 4.66 2.73 18.32 85.35 Testis Clontech 35.81, 40 1.76 0.11 0.94 0.57 87.87 82.16 Thymus Clontech 33.26, 32.49 7.96 12.55 10.26 9.89 5.06 51.85 Thyroid 40, 39.9 0.08 0.16 0.12 2.77 18.05 2.17 Trachea Clontech 34.25, 33.8 4.42 5.77 5.10 9.71 5.15 26.24 Urinary Bladder 39.95, 36.54 0.1 1.14 0.62 5.47 9.14 5.67 Uterus 33, 31.23 9.3 26.52 17.91 5.34 9.36 167.70 genomic 24.72 1251.19 1 1 kn

NO

b-actin 25.89 625.04 1.OOE+05 17.54 10000 1.00E+05 17.65 100000 1.OOE+04 21.03 10000 1.OOE+04 20.92 10000 1.00E+03 24.87 1000 1.OOE+03 24.96 1000 1.00E+02 29.1 100 l.OOE+02 29.04 100 l.OOE+01 32.05 1.00E+01 33.51 1.OOE-00 36.41 1 1.OOE-00 37.41 1 NTC 40 0 NTC 40 -1 Sample Reg Ct Mean copies of Sample Fold sbg1OO7026SGLT number GOI mRNA Change (GSK copies detected/ in identifier 50 ng Disease total Populati RNA on colon normal GW98-167 21941 29.22 127.1 254.20 colon normal colon tumor GW98-166 21940 31.07 44.11 88.22 colon tumor -2.88 colon normal GW98-178 22080 38.41 0.65 1.30 colon normal colon tumor GW98-177 22060 31.17 41.5 83.00 colon tumor 63.85 colon normal GW98-561 23514 31.21 40.69 81.38 colon normal colon tumor GW98-560 23513 33.06 14.04 28.08 colon tumor -2.90 colon normal GW98-894 24691 29.63 100.41 200.82 colon normal colon tumor GW98-893 24690 32.22 22.7 45.40 colon tumor -4.42 lung normal GW98-3 20742 29.8 91.46 182.92 lung normal lung tumor GW98-2 20741 34.26 7.02 14.04 lung tumor -13.03 lung normal GW97-179 20677 29.59 103.13 206.26 lung normal lung tumor GW97-178 20676 29.84 89.09 178.18 lung tumor -1.16 lung normal GW98-165 21922 29.6 102.46 204.92 lung normal lung tumor GW98-164 21921 30.8 51.53 103.06 lung tumor -1.99 lung normal GW98-282 22584 32.53 18.97 37.94 lung normal lung tumor GW98-281 22583 32.29 21.8 43.60 lung tumor 1.15 breast normal GWOO-392 28750 28.77 164.85 164.85 breast normal breast tumor GWOO-391 28746 30.64 56.21 112.42 breast tumor -1.47 breast normal GWOO-413 28798 34.49 6.17 6.17 breast normal breast tumor GWOO-412 28797 30.37 65.97 131.94 breast tumor 21.38 breast normal GWOO- 27592-95 32.87 15.66 15.66 breast normal 235:238 1 breast tumor GW00 27588-91 29.8 91.07 91.07 breast tumor 5.82 231:234 breast normal GW98-621 23656 28.95 149.19 298.38 breast normal breast tumor GW98-620 23655 29.62 101.25 202.50 breast tumor -1.47 brain normal BB99-542 25507 124.5 1917.28 3834.56 brain normal brain normal BB99-406 25509 21.35 11736.92 23473.84 brain normal brain normal BB99-904 25546 25.25 1248.68 2497.36 brain normal brain stage 5 ALZ BB99- 25502 27.29 386.81 773.62 brain stage 5 ALZ -12.84 874 brain stage 5 ALZ BB99- 25503 23.61 3196.37 6392.74 brain stage 5 ALZ -1.55 887 brain stage 5 ALZ BB99- 25504 25.56 1045.09 2090.18 brain stage 5 ALZ -4.75 862 brain stage 5 ALZ BB99- 25542 24.45 1976.24 3952.48 brain stage 5 ALZ -2.51 927 CT lung normal 31.07 44.03 88.06 CT lung Nml lung 26 normal 24.93 1496.87 lung 26 Nml lung 27 normal 34.06 7.92 7.92 lung 27 Nml lung 24 COPD 34.58 5.87 5.87 lung 24 COPD -5.45 lung 28 COPD 40 0 0.00 lung 28 COPD -31.99 lung 23 COPD 40 0 0.00 lung 23 COPD -31.99 lung 25 normal 40 0 0.00 lung 25 Nml asthmatic lung OD03112 29321 33.19 13.04 13.04 asthmatic lung -2.45 asthmatic lung OD03433 29323 30.61 57.38 114.76 asthmatic lung 3.59 asthmatic lung OD03397 29322 29.2 129.16 258.32 asthmatic lung 8.07 asthmatic lung OD04928 29325 30.32 67.67 135.34 asthmatic lung 4.23 endo cells control 35.09 4.37 4.37 endo cells endo VEGF 32.22 22.7 22.70 endo VEGF 5.19 endo bFGF 33.23 12.7 12.70 endo bFGF 2.91 heart Clontech normal 33.53 10.71 21.42 heart heart T-1 ischemic 29417 33.43 11.37 22.74 heart T-1) 1.06 ischemic heart (T-14) non- 29422 34.45 6.32 12.64 heart (T-14) non- -1.69 obstructive DCM obstructive DCM heart (T-3399) DCM 29426 31.98 26.02 52.04 heart (T-3399) 2.43

DCM

adenoid GW99-269 26162 29.56 104.93 209.86 adenoid tonsil GW98-280 22582 29 144.55 289.10 tonsil T cells PC00314 28453 32.03 25.34 50.68 T cells PBMNC 37.71 0.97 0.97 PBMNC monocyte 37.49 1.1 2.20 monocyte B cells PC00665 28455 27.18 410.49 820.98 B cells dendritic cells 28441 33.7 9.73 19.46 dendritic cells neutrophils 28440 32.48 19.6 19.60 neutrophils eosinophils 28446 32.44 20.08 40.16 eosinophils BM unstim 33.8 9.17 9.17 BM unstim BM stim treated 38.89 0.49 0.49 BM stim -18.71 osteo dif treated 37.26 1.26 1.26 osteo dif 1.26 osteo undif 40 0 0.00 osteo undif chondrocytes 32.07 24.82 62.05 chondrocytes OA Synovium IP12/01 29462 30.31 68.26 68.26 OA Synovium OA Synovium NP10/01 29461 30.74 53.26 106.52 OA Synovium OA Synovium NP57/00 28464 31.3 38.48 76.96 OA Synovium RA Synovium NP03/01 28466 31.08 43.89 87.78 RA Synovium RA Synovium NP71/00 28467 31.35 37.58 75.16 RA Synovium RA Synovium NP45/00 28475 30.74 53.21 106.42 RA Synovium OA bone (biobank) 29217 30.47 61.99 61.99 OA bone (biobank) OA bone Sample 1 J. Emory 29.92 85.09 170.18 OA bone OA bone Sample 2 J. Emory 30.91 48.27 96.54 OA bone Cartilage (pool) Normal 31.34 37.68 75.36 Nml Cartilage (pool) Cartilage (pool) OA 31.72 30.35 60.70 OA Cartilage -1.24 (pool) PBL unifected 28441 30.8 51.54 103.08 PBL unifected PBL HIV IIIB 28442 32.03 25.38 50.76 PBL HIV IIIB -2.03 uninfected 29158 32.29 21.85 43.70 MRC5 uninfected (100%) (100%) HSV strain F 29178 31.21 40.73 81.46 MRC5 HSV 1.86 strain F W12 cells 29179 33.12 13.52 27.04 W12 cells Keratinocytes 29180 32.35 21.06 42.12 Keratinocytes B-actin control 25.63 1002.01 genomic 25.19 1290.48 1.00E+05 17.86 100000 1.00E+05 17.85 100000 1.00E+04 21.44 10000 1.OOE+04 21.51 10000 1.OOE+03 25.33 1000 1.00E+03 25.26 1000 1.00E+02 29.62 100 1.OOE+02 30.55 100 1.00E+01 32.93 1.00E+01 33.46 1.00E-00 38.18 1_ 1.00E-00 40 0 NTC 38.28 -1 *lung 26 Normal has been omitted due to multiple amplification failures from that sample Gene Name sbgl007026SGLT Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -2.88 colon tumor 63.85 colon tumor -2.90 colon tumor -4.42 lung tumor -13.03 lung tumor -1.16 lung tumor -1.99 lung tumor 1.15 breast tumor -1.47 breast tumor 21.38 breast tumor 5.82 breast tumor -1.47 brain stage 5 ALZ -12.84 brain stage 5 ALZ -1.55 brain stage 5 ALZ -4.75 brain stage 5 ALZ -2.51 lung 24 -5.45 lung 28 -31.99 lung 23 -31.99 asthmatic lung -2.45 asthmatic lung 3.59 asthmatic lung 8.07 asthmatic lung 4.23 endo VEGF 5.19 endo bFGF 2.91 heart T-1 1.06 heart T-14 -1.69 heart T-3399 2.43 BM stim -18.71 osteo dif 1.26 Cartilage (pool) -1.24 PBL HIV IIIB -2.03 HSV strain F 1.86 Gene Name sbg1012732GLUT High to moderate overall expression. This gene is expressed fairly ubiquitously in all normal samples analyzed with highest levels of expression seen in the whole brain, fetal brain cerebellum, kidney, fetal liver, and the placenta. This gene is also expressed fairly ubiquitously in the disease samples. Downregulation in 3 of 3 COPD samples suggests a potential role for this gene in chronic obstructive pulmonary disorder. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Downregulation in the HSV-infected MRC5 cells suggests that this gene may play a role in HSV. Upregulated in the differentiated osteoblasts. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in the T cells, B cells, dendritic cells, neutrophils, and eosinophils implicates this gene in osteoarthritis and rheumatoid arthritis.

Sample Ct (sample Mean Mean Average 18S 50 copies of sbg1012732GLUT 1 and 2) GOI GOI GOI rRNA ng/18S mRNA copies copies Copies (ng) rRNA detected/ (sample (sample (ng) 50 ng 1) 2) total

RNA

Subcutaneous 30.84, 30.49 46.76 57.63 52.20 3.06 16.34 852.86 Adipocytes Zenbio Subcutaneous Adipose 34.89, 35.19 4.31 3.62 3.97 0.96 52.36 207.59 Zenbio Adrenal Gland Clontech 33.79, 32.74 8.27 15.31 11.79 0.61 81.97 966.39 Whole Brain Clontech 22.02, 21.91 8374.61 8944.05 8659.33 7.24 6.91 59802.00 Fetal Brain Clontech 32.03, 32.85 23.23 14.34 18.79 0.48 103.95 1952.70 Cerebellum Clontech 28.2,28.26 221.12 213.07 217.10 2.17 23.04 5002.19 Cervix 32.91, 34.54 13.81 5.31 9.56 2.42 20.66 197.52 Colon 30.88, 32.48 45.58 17.87 31.73 2.71 18.45 585.33 Endometrium 36.13, 32.5 2.08 17.6 9.84 0.73 68.21 671.21 Esophagus 32.19,33.5 21.15 9.77 15.46 1.37 36.50 564.23 Heart Clontech 31.93, 31.73 24.67 27.76 26.22 1.32 37.88 992.99 Hypothalamus 40, 32.77 0 15.04 7.52 0.32 155.28 1167.70 Ileum 30.94, 30.52 44.17 56.37 50.27 2.58 19.38 974.22 Jejunum 30.04, 29.34 75.03 113.25 94.14 6.60 7.58 713.18 Kidney 29.72,29.18 90.58 124.19 107.39 2.12 23.58 2532.67 Liver 34.81,32.2 4.52 21.05 12.79 1.50 33.33 426.17 Fetal Liver Clontech 26.6, 26.85 567.46 488.36 527.91 10.40 4.81 2538.03 Lung 31.61, 30.52 29.69 56.54 43.12 2.57 19.46 838.81 Mammary Gland 28.06,27.59 239.58 316.2 277.89 13.00 3.85 1068.81 ClontechI Myometrium 30.44,29.88 59.31 82.52 70.92 2.34 21.37 1515.28 Omentum 31.7,30.82 28.2 47.35 37.78 3.94 12.69 479.38 Ovary 30.92,31.56 44.74 30.55 37.65 4.34 11.52 433.70 Pancreas 33.08, 32.66 12.54 16.03 14.29 0.81 61.80 882.88 Head of Pancreas 33.98,34.1 7.36 6.89 7.13 1.57 31.85 226.91 Parotid Gland 29.5, 30.55 102.86 55.41 79.14 5.48 9.12 722.03 Placenta Clontech 25.63, 25.87 1002.18 869.55 935.87 5.26 9.51 8896.06 Prostate 30.23, 31.17 67.04 38.48 52.76 3.00 16.67 879.33 Rectum 31.29, 31.15 35.89 38.94 37.42 1.23 40.65 1520.93 Salivary Gland Clontech 28.82, 28.83 153.9 152.53 153.22 7.31 6.84 1047.98 Skeletal Muscle 33.23, 32.66 11.48 16.02 13.75 1.26 39.68 545.63 Clontech Skin 32.62, 32.57 16.46 16.96 16.71 1.21 41.32 690.50 Small Intestine Clontech 34.63,32.82 5.03 14.62 9.83 0.98 51.07 501.79 Spleen 31.45, 32.71 32.66 15.56 24.11 4.92 10.16 245.02 Stomach 32.38, 32.43 18.93 18.41 18.67 2.73 18.32 341.94 Testis Clontech 32.32, 32.27 19.58 20.17 19.88 0.57 87.87 1746.49 Thymus Clontech 27.24, 26.75 388.32 518.55 453.44 9.89 5.06 2292.39 Thyroid 30.48,29.44 57.86 106.5 82.18 2.77 18.05 1483.39 Trachea Clontech 29.96, 30.29 78.48 64.81 71.65 9.71 5.15 368.92 Urinary Bladder 30.59, 30.1 54.25 72.45 63.35 5.47 9.14 579.07 Uterus 30.62,29.73 53.18 89.72 71.45 5.34 9.36 669.01 genomic 25.15 1330.24 b-actin 26.01 800.58 1.00E+05 18.01 100000 1.OOE+05 18.19 100000 1.OOE+04 21.35 10000 1.00E+04 21.3 10000 1.00E+03 25.59 1000 1.00E+03 25.51 1000 1.00E+02 29.95 100 1.OOE+02 29.37 100 1.OOE+01 34.05 1.00E+01 33.22 1.00E-00 37.19 I 1.OOE-00 40 0 NTC 40 0 NTC 140 Sample Reg Ct Mean copies of Sample Fold sbgTO12732GLUT number GOT niRNA Change (GSK copies detected/ in identifier 50 ug Disease )total Populati RNA colon normal GW98-167 21941 25.38 1695.47 3390.94 colon normal colon tumor GW98- 166 21940 25.51 1576.91 3153.82 colon tumor -1.08 colon normal GW98-178 22080 26.8 765.5 1531.00 colon normal colon tumor GW98- 177 22060 25.86 1297.34 2594.68 colon tumor A1.69 colon normal GW98-561 23514 26.12 1120.6412241.28 colon normal colon tumor GW98-560 23513 26.12 1121.8912243.78 colon tumor 1.00 colon normal GW98-894 24691 .24.85 2283.5614567.12 colon normal colon tumor GW98-893 24690 24.37 2989.5 5979.00 colon tumor 1.31 lung normal GW98-3 20742 24.37 2984.11 5968.22 lung normal lung tumor GW98-2 20741 25.38 1691.06 3382.12 lung tumor -1.76 lung normal GW97-179 20677 25.07 12020.52 4041.04 lung normal lung tumor GW97- 178 20676 24.61 2607.03 5214.06 lung tumor 1.29 lung normal GW98- 165 21922 24.92 2195.85 4391.70 lung normal lung tumor GW98-164 21921 25.36 1712.62 3425.24 lung tumor -1.28 lung normal GW98-282 22584 26.24 1049.97 2099.94 lung normal lung tumor GW98-281 22583 25.94 11241.8 2483.60 lung tumor 1.18 breast normal GWOO-392 28750 25.26 1813.7 1813.70 breast normal breast tumor GWOO-391 28746 24.87 2259.54 4519.08 breast tumor 2.49 breast normal GW00-413 28798 25.4 1672.46 1672.46 breast normal breast tumor GWOO-412 28797 25.21 1864.18,3728.36 breast tumor 2.23 breast normal GWOO- 27592-95 25.68 1435.2 1435.20 breast normal 235:238 1 i__ breast tumor GWOO- 27588-91 24.08 3510.7813510.78 breast tumor 2.45 231:234 breast normal GW98-621 23656 24.16 3363.2616726.52 breast normal breast tumor GW98-620 23655 24.19 3300.23 16600.46 breast tumor -1.02 brain normal BB99-542 25507 22.64 7880.57 15761.14 brain normal brain normal BB99-406 25509 23.32 5357.05 10714.10 brain normal brain normal BB99-904 25546 23.66 4436.27 8872.54 brain normal brain stage 5 ALZ BB99- 25502 24.7 2474.23 4948.46 brain stage 5 ALZ -2.38 874 brain stage 5 ALZ BB99- 25503 23.22 5674.88 11349.76 brain stage 5 ALZ -1.04 887 brain stage 5 ALZ BB99- 2554 23.5 4868.6 9737.20 brain stage 5 ALZ -1.21 862 brain stage 5 AIZ BB99- 25542 23.17 5843.2 11686.40 brain stage 5 ALZ -1.01 927 CT lung normal 25.61 1486.99 2973.98 CT lung Nml lung 26 normal 26.55 879.91 26 Nm lung 27 normal 129.44 174.3 174.30 lung 27 Nmld

I

lung 24 COPD 29.99 128.5 128.50 lung 24 COPD -8.67 lung 28 COPD 29.56 163.34 163.34 lung 28 COPD -6.82 lung 23 COPD 29.59 160.67 160.67 lung 23 COPD -6.94 lung 25 normal 29.24 194.83 194.83 lung 25 Nml asthmatic lung OD03112 29321 27.22 604.38 604.38 asthmatic lung -1.84 asthmatic lung OD03433 29323 26.46 923.43 1846.86 asthmatic lung 1.66 asthmatic lung OD03397 29322 26.16 1094.36 2188.72 asthmatic lung 1.96 asthmatic lung OD04928 29325 25.51 1576.72 3153.44 asthmatic lung 2.83 endo cells control 29.09 211.78 211.78 endo cells endo VEGF 30.07 122.67 122.67 endo VEGF -1.73 endo bFGF 29.93 132.63 132.63 endo bFGF -1.60 heart Clontech normal 27.35 561.26 1122.52 heart heart( T-1) ischemic 29417 23.82 4053.65 8107.30 heart 7.22 Sischemic heart (T-14) non- 29422 23.96 3746.25 7492.50 heart (T-14) non- 6.67 obstructive DCM obstructive DCM heart (T-3399) DCM 29426 23.35 5282.35 10564.70 heart (T-3399) 9.41

DCM

adenoid GW99-269 26162 25.71 1405.41 2810.82 adenoid tonsil GW98-280 22582 23.97 3725.77 7451.54 tonsil T cells PC00314 28453 25.03 2062.68 4125.36 T cells PBMNC 30.16 116.69 116.69 PBMNC monocyte 30.15 117.05 234.10 monocyte B cells PC00665 28455 23.22 5673.63 11347.26 B cells dendritic cells 28441 25.74 1385.65 2771.30 dendritic cells neutrophils 28440 27.14 631.86 631.86 neutrophils eosinophils 28446 28.27 335.66 671.32 eosinophils BM unstim 30.08 122.25 122.25 BM unstim BM stim treated 29.57 162.71 162.71 BM stim 1.33 osteo dif treated 29.07 214.84 214.84 osteo dif 2.91 osteo undif 30.98 73.85 73.85 osteo undif chondrocytes 25.41 1667.28 4168.20 chondrocytes OA Synovium IP12/01 29462 24.65 2554.39 2554.39 OA Synovium OA Synovium NP10/01 29461 25.72 1399 2798.00 OA Synovium OA Synovium NP57/00 28464 25.24 1828.2 3656.40 OA Synovium RA Synovium NP03/01 28466 25.69 1422.61 2845.22 RA Synovium RA Synovium NP71/00 28467 25.25 1818.15 3636.30 RA Synovium RA Synovium NP45/00 28475 25.22 1857.13 3714.26 RA Synovium OA bone (biobank) 29217 26.19 1074.74 1074.74 OA bone (biobank) OA bone Sample 1 J. Emory 26.71 805.65 1611.30 OA bone OA bone Sample 2 J. Emory 26.96 700.88 1401.76 OA bone Cartilage (pool) Normal 26.38 968.45 1936.90 Nml Cartilage Cartilage (pool) OA 28.07 376.23 752.46 OA Cartilage -2.57 __(pool) PBL unifected 28441 25.09 1997.75 3995.50 PBL unifected PBL HIV IIB 28442 25.36 1710.81 3421.62 PBL HIV IB -1.17 uninfected 29158 25.28 1788.71 3577.42 MRC5 uninfected (100%) HSV strain F 29178 30.17 116.17 232.34 MRC5 HSV strain -15.40

F

W12 cells 29179 27.6 489.01 978.02 W12 cells Keratinocytes 29180 26.4 959.61 1919.22 Keratinocytes B-actin control 25.62 1482.86 genomic 25.42 1657.68 1.OOE+05 18.49 100000 1.00E+05 18.49 100000 1.00E+04 21.94 10000 1.00E+04 21.98 10000 1.00E+03 25.34 1000 1.00E+03 25.39 1000 1.00E+02 30.59 100 1.00E+02 30.9 100 1.00E+01 32.51 1.00E+01 39.12 1.OOE-00 39.07 1 1.OOE-00 36.71 1 NTC 39.63 -1 *lung 26 Normal has been omitted due to multiple amplification failures from that sample Gene Name sbgl012732GLUT Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -1.08 colon tumor 1.69 colon tumor 1.00 colon tumor 1.31 lung tumor -1.76 lung tumor 1.29 lung tumor -1.28 lung tumor 1.18 breast tumor 2.49 breast tumor 2.23 breast tumor 2.45 breast tumor -1.02 brain stage 5 ALZ -2.38 brain stage 5 ALZ -1.04 brain stage 5 ALZ -1.21 brain stage 5 ALZ -1.01 lung 24 -8.67 lung 28 -6.82 lung 23 -6.94 asthmatic lung -1.84 asthmatic lung 1.66 asthmatic lung 1.96 asthmatic lung 2.83 endo VEGF -1.73 endo bFGF -1.60 heart T-1 7.22 heart T-14 6.67 heart T-3399 9.41 BM stim 1.33 osteo dif 2.91 Cartilage (pool) -2.57 PBL HIV IlB -1.17 HSV strain F -15.40 Gene Name sbgl012732GLUTb The same as sbg1012732GLUT.

Gene Name sbgl018172CSP Moderate to low overall expression. Highest normal expression is seen in the whole brain, kidney, thyroid, and uterus. This gene is expressed in all of the samples representing the female reproductive system. Highest disease expression is seen in many of the normal/tumor lung samples and the asthmatic lung samples. Downregulation in 2 of 4 lung tumor samples and upregulation in 2 of 4 breast tumor samples suggests an involvement in cancers of the lung and breast.

Downregulation in 3 of 3 COPD samples suggests a potential role for this gene in chronic obstructive pulmonary disorder. Upregulation in 2 of 4 asthmatic lung samples implies an involvement in asthma. Upregulation in 1 of 3 disease heart samples implies an involvement in cardiovascular disease such as obstructive DCM. Downregulation in the OA cartilage pool with corroborating low expression in the immune cells (T and B cells in particular) implicates this gene in osteoarthritis and rheumatoid arthritis. Upregulation in the HSV-infected MRCS cells suggests that this gene may be a host factor in HSV.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg1018172CSP 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 35.54, 34.87 7.65 11.21 9.43 3.06 16.34 154.08 Adipocytes Zenbio Subcutaneous Adipose 40,40 0.4 0 0.20 0.96 52.36 10.47 Zenbio Adrenal Gland Clontech 40,40 0 0 0.00 0.61 81.97 0.00 Whole Brain Clontech 25.71,25.78 1950.98 1867.58 1909.28 7.24 6.91 13185.6 4 Fetal Brain Clontech 40,40 0 0 0.00 0.48 103.95 0.00 Cerebellum Clontech 36.32, 35.16 4.95 9.48 7.22 2.17 23.04 166.24 Cervix 36.76, 36.16 3.85 5.42 4.64 2.42 20.66 95.76 Colon 36.52, 36.41 4.41 4.7 4.56 2.71 18.45 84.04 Endometrium 36.4,35.92 4.73 6.19 5.46 0.73 68.21 372.44 Esophagus 40, 40 0 0 0.00 1.37 36.50 0.00 Heart Clontech 40, 40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40,40 0 0 0.00 0.32 155.28 0.00 Ileum 40, 40 0 0 0.00 2.58 19.38 0.00 Jejunum 36.53, 33.22 4.38 28.28 16.33 6.60 7.58 123.71 Kidney 32.81, 32.45 35.74 43.67 39.71 2.12 23.58 936.44 Liver 35.92,36.2 6.19 5.29 5.74 1.50 33.33 191.33 Fetal Liver Clontech 31.57,30.46 71.69 134.34 103.02 10.40 4.81 495.26 Lung 33.35, 36.86 26.32 3.65 14.99 2.57 19.46 291.54 Mammary Gland 32.99, 32.17 32.23 51.27 41.75 13.00 3.85 160.58 Clontech

I

Myometrium 34.99,40 10.44 0 5.22 2.34 21.37 111.54 Omenturnm 35.61,40 7.37 0 3.69 3.94 12.69 46.76 Ovary 35.83, 35.54 6.53 7.67 7.10 4.34 11.52 81.80 Pancreas 35.86,40 6.39 0 3.20 0.81 61.80 197.47 Head of Pancreas 40,40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 34.26,34.03 15.73 17.96 16.85 5.48 9.12 153.70 Placenta Clontech 32.64,33.16 39.34 29.26 34.30 5.26 9.51 326.05 Prostate 35.71,40 6.95 0 3.48 3.00 16.67 57.92 Rectum 33.84, 34.42 19.99 14.41 17.20 1.23 40.65 699.19 Salivary Gland 40,40 0 0 0.00 7.31 6.84 0.00 Clontech Skeletal Muscle 34.2,40 16.33 0 8.17 1.26 39.68 324.01 Clontech Skin 35.02, 40 10.31 0.48 5.40 1.21 41.32 222.93 Small Intestine 40,40 0 0 0.29 0.98 51.07 14.81 Clontech____ Spleen 40,35.31 0 8.71 4.36 4.92 10.16 44.26 Stomach 40,35.4 0 8.3 4.15 2.73 18.32 76.01 Testis Clontech 40,37.31 0 2.82 1.41 0.57 87.87 123.90 Thymus Clontech 30.9, 31.1 104.45 93.52 98.99 9.89 5.06 500.43 Thyroid 31.62,31.57 69.89 71.93 70.91 2.77 18.05 1279.96 Trachea Clontech 34.19, 34.08 16.41 17.49 16.95 9.71 5.15' 87.28 Urinary Bladder 40, 34.4 0 14.55 7.28 5.47 9.14 66.50 Uterus 30.63,30.6 122.13 123.57 122.85 5.34 9.36 1150.28 genomic 26.58 1190.6 b-actin 27.38 758.43 1.00E+05 19.07 100000 1.00E+05 19.35 100000 1.00E+04 22.57 10000 1.00E+04 22.59 10000 1.00E+03 26.24 1000 1.00E+03 26.31 1000 1.00E+02 30.18 100 1.00E+02 31.64 100 l.OOE+01 35.9 l.OOE+01 40 0 1.00oE-00 40 0 1.00E-00 40 0 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies of Sample Fold isbglO18172CSP nmber I GOI mRNA I Change (GSK copies detected/ in identifier 50 ng Disease )total Populati ___RNA colon normal GW98-167 21941 27.29 1064.89 2129.78 colon normal colon tumor GW98-166 21940 26.18 2023.11 4046.22 colon tumor 1.90 colon normal GW98-178 22080 30.45 168.68 337.36 colon normal colon tumor GW98-177 22060 29.33 324.49 648.98 colon tumor 1.92 colon normal GW98-561 23514 30.36 177.62 355.24 colon normal colon tumor GW98-560 23513 32.27 58.7 1117.40 colon tumor -3.03 colon normal GW98-894 24691 30.71 145.57 291.14 colon normal colon tumor GW98-893 24690 32.3 57.43 114.86 colon tumor -2.53 lung normal GW98-3 20742 24.82 4478.67 8957.34 lung normal lung tumor GW98-2 20741 33.61 26.86 53.72 lung tumor -166.74 lung normal GW97- 179 20677 26.31 1874.25 3748.50 lung normal lung tumor GW97-178 20676 24.52 15311.72 10623.44 lung tumor 2.83 lung normal GW98- 165 21922 24.99 14042.28 8084.56 lung normal lung tumor GW98-164 21921 27.19 1127.26 2254.52 lung tumor 1-3.59 lung normal GW98-282 22584 25.51 2990.53 5981.06 lung normal lung tumor GW98-281 22583 26.67 1522.51 3045.02 lung tumor -1.96 breast normal GWOO-392 28750 32.25 59.17 59.17 breast normal breast tumor GWOO-391 28746 30.48 165.82 331.64 breast tumor 5.60 breast normal GWOO-413 28798 34.58 15.31 15.31 breast normal breast tumor GWOO-412 28797 30.05 213.4 426.80 breast tumor 27.88 breast normal GWOO- 27592-95 34.41 16.85 16.85 breast normal 235:238 breast tumor GWOO- 27588-91 33.52 28.31 28.31 breast tumor 1.68 231:2-34 breast normal GW98-621 23656 28.22 618.19' 1236.38 breast normal breast tumor GW98-620 23655 32.02 67.94 135.88 breast tumor -9.10 brain normal BB99-542 2550Y7 29.11 367.88 735.76 brain normal brain normal BB99-406 25509 28.05 682.39 1364.78 brain normal brain normal BB99-904 25546 29.06 379.07 1758.14 brain normal brain stage 5 ALZ BB99- 25502 30.06 211.81 1423.62 brain stage 5 ALZ -2.25I 874 brain stage 5 ALZ BB99- 25503 26.97 1280.13 12560.26 brain stage 5 ALZ 2.69 887 brain stage 5 ALZ BB99- 25504 29.85 239.03 478.06 brain stage 5 ALZ -1.99 862 brain stage 5 ALZ BB99- 25542 '28.13 652.56 1305.12 brain stage 5 ALZ 1.37 927 CT lung normal 26.97 1280.81 2561.62 CT lung Nml lung 26 normal 32.21 60.75 26 Nml lung 27 normal 34 21.39 21.39 lung 27 Nml lung 24 COPD 32.11 64.11 64.11 lung 24 COPD -1 3.87 lung 28 COPD 33.01 38.18 38.18 lung 28 CQPD -23.29 lung 23 COPD 32.84 42.15 142.15 lung 23 COPDI -21.10 lung 25 normal 31.63 84.78 84.78 lung 25 Nml asthmatic lung 0D031 12129321 29.4 310.75 310.75 asthmatic lung 1-2.86 ashai lug104329323 27.02 11242.79 2485.58 1asthmnatic lung 12.80 asthmatic lung OD03397 29322 25.97 2289.74 4579.48 asthmatic lung 5.15 asthmatic lung OD04928 29325 26.84 1380.5 2761.00 asthmatic lung 3.10 endo cells control 40 0 0.00 endo cells endo VEGF 40 0 0.00 endo VEGF 0.00 endo bFGF 40 1.01 1.01 endo bFGF 1.01 heart Clontech normal 33.02 37.93 75.86 heart heart( T- ischemic 29417 34.34 17.51 35.02 heart -2.17 ischemic heart (T-14) non- 29422 34.85 13.07 26.14 heart (T-14) non- -2.90 obstructive DCM obstructive DCM heart (T-3399) DCM 29426 29.74 254.69 509.38 heart (T-3399) 6.71

DCM

adenoid GW99-269 26162 35.07 11.5 23.00 adenoid tonsil GW98-280 22582 40 0 0.00 tonsil Tcells PC00314 28453 36.12 6.22 12.44 T cells PBMNC 40 0 0.00 PBMNC monocyte 40 0 0.00 monocyte B cells PC00665 28455 40 0 0.00 B cells dendritic cells 28441 40 0 0.00 dendritic cells neutrophils 28440 35.43 9.3 9.30 neutrophils eosinophils 28446 40 1.32 2.64 eosinophils BM unstim 40 0 0.00 BM unstim BM stim treated 40 0 0.00 BM stim 0.00 osteo dif treated 40 0 0.00 osteo dif 0.00 osteo undif 40 0 0.00 osteo undif chondrocytes 33.23 33.49 83.73 chondrocytes OA Synovium IP12/01 29462 34.9 12.68 12.68 OA Synovium OA Synovium NP10/01 29461 28.55 510.63 1021.26 OA Synovium OA Synovium NP57/00 28464 34 21.41 42.82 OA Synovium RA Synovium NP03/01 28466 40 0 0.00 RA Synovium RA Synovium NP71/00 28467 36.2 5.96 11.92 RA Synovium RA Synovium NP45/00 28475 36.38 5.34 10.68 RA Synovium OA bone (biobank) 29217 35.58 8.52 8.52 OA bone 33.5 (biobank) OA bone Sample 1 J. Emory 33.54 27.91 55.82 OA bone OA bone Sample 2 J. Emory 34.92 12.54 25.08 OA bone Cartilage (pool) Normal 33.88 22.98 45.96 Nml Cartilage (pool) Cartilage (pool) OA 40 0 0.00 OA Cartilage -45.96 (pool) PBL unifected 28441 30.74 142.65 285.30 PBL unifected PBL HIV IIIB 28442 32.47 52.13 104.26 PBL HIV IIB -2.74 uninfected 29158 40 0 0.00 MRC5 uninfected (100%) (100%) HSV strain F 29178 30.06 211.88 423.76 MRC5 HSV 423.76 strain F W12 cells 29179 39.65 0.8 1.60 W12 cells Keratinocytes 29180 33.76 24.58 49.16 Keratinocytes B-actin control 27.17 1140.82 genomic 26.81 1405.46 1.OOE+05 19.68 1O00 1.OOE+05 19.63 100000 1.OOE+04 23.15 10000 1.OOE+04 23.27 10000 1.00E+03 27.1 11000 1.OOE+03 27.33 1000 1.OOE+02 31.34 100 1.OOE+02 100 1.OOE+01 10 1.OOE+01 40 110 40 10 1.00E-00 40 10 NTC 40 0 *lung 26 Normal has been omaitted due to multiple amplification failures from that sample Gene Name sbglOl 8172CSP Disease tissues Fold Change in Disease Population Relative to Normal colon rumor 1.90 colon tumor 1.92 colon tumor -3.03 colon tumor -2.53 lung tumor -166.74 lung tumor' 2.83 lung tumor -3.59 -lung tumor -1.96 -breast tumor 5.60 -breast tumor 27.88 breast tumor 1.68 breast tumor -9.10 brain stage 5 ALZ -2.25 brain stage 5 ATLZ 2.69 brain stage 5ALZ -1.99 brain stage 5 ATZ 1.37 lung 24 13.87 lung 28 -32 lung 23 -11 asthmatic lung-28 asthmatic lung 29 asthmatic lung 51 asthmatic lung 31 endo VEGF.00 endo bPGF 1.01 heart T-1 -2.17 heart T- 14 -2.90 heart T-3399 6.71 BM stim, 0.00 osteo dif 0.00 Cartilage (ool) -45.96 I PBL HIV MUB 1 -2.74 HSV strain F 423.76 Gene Name sbg1004570ERGIC Moderate to low overall expression. This gene is expressed fairly ubiquitously in all normal samples analyzed with highest levels of expression seen in the whole brain, hypothalamus, pancreas, and head of pancreas. This pattern of expression suggests that this gene may be involved in diabetes or other metabolic diseases. Highest disease expression is seen in the colon, breast, and lung normal/tumor pairs as well as the Alzheimer's brain samples and the T cells, B cells, dendritic cells, and eosinophils. Upregulation in 2 of 4 breast tumor samples suggests a role for this gene in breast cancer. Upregulation in 2 of 4 Alzheimer's brain samples implies an involvement in Alzheimer's disease. Downregulation in 3 of 3 COPD samples and 4 of 4 asthmatic lung samples suggests a potential role for this gene in chronic obstructive pulmonary disorder and asthma.

Upregulated in the stimulated bone marrow sample.

Sample Ct (sample Mean Mean Average 18S 50 copies sbg1004570ERGIC 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total

RNA

Subcutaneous 40, 40 0 0 0.00 3.06 16.34 0.00 Adipocytes Zenbio Subcutaneous Adipose 39.46, 35.22 0.08 1.37 0.73 0.96 52.36 37.96 Zenbio Adrenal Gland Clontech 36.91, 36.21 0.43 0.7 0.57 0.61 81.97 46.31 Whole Brain Clontech 26.46, 30.31 547.02 39.49 293.26 7.24 6.91 2025.24 Fetal Brain Clontech 36.04, 36.66 0.78 0.51 0.65 0.48 103.95 67.05 Cerebellum Clontech 35.46,34.63 1.16 2.06 1.61 2.17 23.04 37.10 Cervix 35.63, 36.28 1.04 0.67 0.86 2.42 20.66 17.67 Colon 35.38, 34.57 1.23 2.13 1.68 2.71 18.45 31.00 Endometrium 40, 35.24 0.06 1.35 0.71 0.73 68.21 48.09 Esophagus 35.02, 36.31 1.57 0.65 1.11 1.37 36.50 40.51 Heart Clontech 37.16, 35.48 0.36 1.15 0.76 1.32 37.88 28.60 Hypothalamus 35.15, 36.01 1.44 0.8 1.12 0.32 155.28 173.91 Ileum 35.04, 35.5 1.55 1.13 1.34 2.58 19.38 25.97 Jejunum 35.14, 34.88 1.45 1.73 1.59 6.60 7.58 12.05 Kidney 35.81, 37.16 0.91 0.36 0.64 2.12 23.58 14.98 Liver 36.19, 34.39 0.71 2.42 1.57 1.50 33.33 52.17 Fetal Liver Clontech 32.94, 33.1 6.51 5.85 6.18 10.40 4.81 29.71 Lung 34.54, 35.16 2.18 1.43 1.81 2.57 19.46 35.12 Mammary Gland 34.45, 34.76 2.33 1.88 2.11 13.00 3.85 8.10 Clontech I Myometrium 34.08, 34.61 2.98 2.09 2.54 2.34 21.37 54.17 Omentum 35.22, 36.18 1.37 0.71 1.04 3.94 12.69 13.20 Ovary 34.52, 34.83 2.21 1.78 2.00 4.34 11.52 22.98 Pancreas 34.45, 33.99 2.32 3.18 2.75 0.81 61.80 169.96 Head of Pancreas 33.24, 33.63 5.32 4.06 4.69 1.57 31.85 149.36 Parotid Gland 33.22, 33.08 5.38 5.9 5.64 5.48 9.12 51.46 Placenta Clontech 36.02,35.39 0.79 1.22 1.01 5.26 9.51 19.55 Prostate 35.98,35.07 0.81 1.51 1.16 3.00 16.67 19.33 Rectum 36.71, 37.13 0.49 0.37 0.43 1.23 40.65 17.48 Salivary Gland Clontech 33.51, 34.22 4.41 2.71 3.56 7.31 6.84 24.35 Skeletal Muscle Clontech 35.53, 34.52 1.11 2.21 1.66 1.26 39.68 65.87 Skin 36.02,36.07 0.79 0.77 0.78 1.21 41.32 32.23 Small Intestine Clontech 35.02, 37.21 1.57 0.35 0.96 0.98 51.07 49.03 Spleen 35.64,35.27 1.03 1.33 1.18 4.92 10.16 11.99 Stomach 35.08, 35.41 1.51 1.2 1.36 2.73 18.32 24.82 Testis Clontech 35.48, 38.1 1.15 0.19 0.67 0.57 87.87 58.88 Thymus Clontech 32.15, 31.72 11.16 14.98 13.07 9.89 5.06 66.08 Thyroid 35.61, 35.09 1.05 1.49 1.27 2.77 18.05 22.92 Trachea Clontech 35.04, 34.75 1.55 1.89 1.72 9.71 5.15 8.86 Urinary Bladder 36.11, 36.24 0.74 0.68 0.71 5.47 9.14 6.49 Uterus 35.59, 35.68 1.06 1 1.03 5.34 9.36 9.64 genomic 24.29 b-actin 26.09 706.6 1.OOE+05 20.09 100000 1.00E+05 19.53 1.00E+04 21.72 10000 1.00E+04 21.68 10000 1.00E+03 24.13 1.00E+03 24.18 1000____ 1.00E+02 29.13 1.00E+02 30.16 1.00E+01 31.7 10 1.00E+01 33.16 1.OOE-00 36.93 1 1.00E-00 34.75 NTC 36 -1 NTC_ j___35.85 Sample Reg Ct Mean copies Sample Fold sbg1004570ERGIC number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populati total on colon normal GW98-167 21941 30.51 38.25 76.50 colon normal colon tumor GW98-166 21940 31.28 23.13 46.26 colon tumor -1.65 colon normal GW98-178 22080 31.79 16.57 33.14 colon normal colon tumor GW98-177 22060 31.3 22.86 45.72 colon tumor 1.38 colon normal GW98-561 23514 30.71 33.5 67.00 colon normal colon tumor GW98-560 23513 31.18 24.73 49.46 colon tumor -1.35 colon normal GW98-894 24691 30.16 48.2 96.40 colon normal colon tumor GW98-893 24690 29.96 55 110.00 colon tumor 1.14 lung normal GW98-3 20742 30.1 50.19 100.38 lung normal lung tumor GW98-2 20741 32.86 8.15 16.30 lung tumor -6.16

IND

0 kn

IN

lung normal GW97-179 20677 31.65 18.14 36.28 lung normal lung tumor GW97-178 20676 31.05 26.89 53.78 lung tumor 1.48 lung normal GW98-165 21922 30.44 40.16 80.32 lung normal lung tumor GW98-164 21921 30.72 33.36 66.72 lungtumor -1.20 lung normal GW98-282 22584 31.83 16.13 32.26 lung normal lungtumorGW98-281 22583 32.09 13.61 27.22 lungtumor -1.19 breast normal GWOO-392 28750 32.76 8.73 8.73 breast normal breast tumor GWOO-391 28746 30.68 34.38 68.76 breast tumor 7.88 breast normal GW0O-413 28798 37.11 0.5 0.50 breast normal breast tumor GWOO-412 28797 30.8 31.72 63.44 breast tumor 126.88 breast normal GWOO- 27592-95 38.8 0.17 0.17 breast normal 235:238 1 breast tumor GWOO- 27588-91 37.36 0.43 0.43 breast tumor 2.53 231:234 breast normal GW98-621 23656 31.67 17.86 35.72 breast normal breast tumor GW98-620 23655 32.59 9.8 19.60 breast tumor -1.82 brain normal BB99-542 25507 33.66 4.83 9.66 brain normal brain normal BB99-406 25509 33.24 6.37 12.74 brain normal brain normal BB99-904 25546 33.2 6.54 13.08 brain normal brain stage 5 ALZ BB99- 25502 33.1 6.97 13.94 brain stage 5 ALZ 1.18 874 1 brain stage 5 ALZ BB99- 25503 30.93 29.17 58.34 brain stage 5 ALZ 4.93 887 brain stage 5 ALZ BB99- 25504 31.44 20.73 41.46 brain stage 5 ALZ 3.51 862 brain stage 5 ALZ BB99- 25542 32.93 7.83 15.66 brain stage 5 ALZ 1.32 927 CT lung normal 32.62 9.6 19.20 CT lung NmI lung 26 normal lung 26 Nml lung 27 normal 40 0 0.00 lung 27 Nml lung 24 COPD 39.15 0.13 0.13 lung 24 COPD -49.46 lung 28 COPD 40 0.08 0.08 lung 28 COPD -80.38 lung 23 COPD 38.59 0.19 0.19 lung 23 COPD -33.84 lung 25 normal 40 0.09 0.09 lung 25 Nml asthmatic lung OD03112 29321 40 0 0.00 asthmatic lung -6.43 asthmatic lung 0D03433 29323 38.47 0.2 0.40 asthmatic lung -16.08 asthmatic lung OD03397 29322 38.01 0.28 0.56 asthmatic lung -11.48 asthmatic lung OD04928 29325 38.13 0.26 0.52 asthmatic lung -12.37 endo cells control 36.24 0.89 0.89 endo cells endo VEGF 39.8 0.09 0.09 endo VEGF -9.89 endo bFGF _37.19 0.47 0.47 endo bFGF -1.89 heart Clontech normal 35.52 1.43 2.86 heart heart T-I ischemic 29417 33.79 4.43 8.86 heart( T- 3.10 I_ ischemic heart (T-14) non- 29422 34.81 2.27 4.54 heart (T-14) non- 1.59 obstructive DCM obstructive DCM heart (T-3399) DCM 29426 34.11 3.59 7.18 heart (T-3399) 2.51

DCM

adenoid GW99-269 26162 34.97 2.05 4.10 adenoid tonsil GW98-280 22582 33.05 7.23 14.46 tonsil T cells PC00314 28453 31.09 26.2 52.40 T cells PBMNC 38.01 0.28 0.28 PBMNC monocyte 36.29 0.86 1.72 monocyte B cells PC00665 28455 32.13 13.23 26.46 B cells dendritic cells 28441 31.94 14.96 29.92 dendritic cells neutrophils 28440 34.08 3.66 3.66 neutrophils eosinophils 28446 32.23 12.37 24.74 eosinophils BM unstim 39.73 0.09 0.09 BM unstim BM stim treated 37.03 0.53 0.53 BM stim 5.89 osteo dif treated 36.8 0.61 0.61 osteo dif 0.61 osteo undif 40 0 0.00 osteo undif chondrocytes 31.85 15.9 39.75 chondrocytes OA Synovium IP12/01 29462 38.61 0.19 0.19 OA Synovium OA Synovium NP10/01 29461 33.11 6.96 13.92 OA Synovium OA Synovium NP57/00 28464 33.81 4.39 8.78 OA Synovium RA Synovium NPO3/01 28466 33.11 6.96 13.92 RA Synovium RA Synovium NP71/00 28467 32.03 14.14 28.28 RA Synovium RA Synovium NP45/00 28475 32.47 10.55 21.10 RA Synovium OA bone (biobank) 29217 35.25 1.7 1.70 OA bone (biobank) OA bone Sample 1 J. Emory 34.54 2.72 5.44 OA bone OA bone Sample 2 J. Emory 36.28 0.87 1.74 OA bone Cartilage (pool) Normal 35.24 1.71 3.42 Nml Cartilage (pool) Cartilage (pool) OA 34.45 2.87 5.74 OA Cartilage 1.68 (pool) PBL unifected 28441 32.53 10.19 20.38 PBL unifected PBL HIV IIIB 28442 31.77 16.79 33.58 PBL HIV IIIB 1.65 MRCS uninfected 29158 33.12 6.87 13.74 MRCS uninfected (100%) (100%) MRCS HSV strain F 29178 33.76 4.54 9.08 MRC5 HSV strain -1.51

F

W12 cells 29179 33.1 6.96 13.92 W12 cells Keratinocytes 29180 32.67 9.29 18.58 Keratinocytes B-actin control 26.03 726.55 genomic 24.63 1825.58 1.00E+05 19.96 100000 1.00E+05 19.27 100000 1.00E+04 21.83 10000 1.00E+04 21.45 10000 1.00E+03 23.86 1000 1.00E+03 23.84 1000 1.00E+02 28.42 100 1.00E+02 29.35 100 1.00E+01 33.3 1.00E+01 35.09 1.00E-00 35.16 1 1.00E-00 36.05 1 NTC 38.24 -1 *lung 26 Normal has been omitted due to multiple amplification failures from that sample Gene Name sbg1004570ERGIC Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -1.65 colon tumor 1.38 colon tumor -1.35 colon tumor 1.14 lung tumor -6.16 lung tumor 1.48 lung tumor -1.20 lung tumor -1.19 breast tumor 7.88 breast tumor 126.88 breast tumor 2.53 breast tumor -1.82 brain stage 5 ALZ 1.18 brain stage 5 ALZ 4.93 brain stage 5 ALZ 3.51 brain stage 5 ALZ 1.32 lung 24 -49.46 lung 28 -80.38 lung 23 -33.84 asthmatic lung -6.43 asthmatic lung -16.08 asthmatic lung -11.48 asthmatic lung -12.37 endo VEGF -9.89 endo bFGF -1.89 heart T-1 3.10 heart T-14 1.59 heart T-3399 2.51 BM stim 5.89 osteo dif 0.61 Cartilage (pool) 1.68 PBL HIV IIIB 1.65 HSV strain F -1.51 Gene Name sbgl016995IGBrecpt Moderate to low overall expression. Highest normal expression is seen in the whole brain in lung with slightly lower levels of expression in the endometrium, ileum, rectum, and skin. High level of expression in the skin may suggest a possible role for this gene in psoriasis and Lupus. The patterns of expression in the samples on the disease plate indicate that this gene is highly specific to the adenoid and tonsil. Downregulation in 2 of 4 lung tumor samples and upregulation in 2 of 4 breast tumor samples suggests an involvement in cancers of the lung and breast Downregulation in 3 of 3 COPD samples suggests a potential role for this gene in chronic obstructive pulmonary disorder. Upregulated in the stimulated bone marrow sample.

Downregulated in the differentiated osteoblast Upregulated in the HIV-infected PBL cells suggests that this gene may be a host factor in HIV.

ISample I Ct (sample Mean IMean Average 18S 150 I copies of I sbgO1699SIGBrecpt I and 2) GOI GOI GOI rRNA ng/18S mRNA copies copies Copies (ng) rRNA detected/ (sample (sample (ng) 50 ng 1) 2) total

RNA

Subcutaneous 40, 40 0.61 0.61 0.61 3.06 16.34 9.97 Adipocytes Zenbio Subcutaneous Adipose 40, 40 0.59 0.56 0.58 0.96 52.36 30.10 Zenbio Adrenal Gland 39.89, 39.79 0.54 0.57 0.56 0.61 81.97 45.49 Clontech I I Whole Brain Clontech 30.69, 30.76 108.67 104.35 106.51 7.24 6.91 735.57 Fetal Brain Clontech 39.41, 40 0.71 0.62 0.67 0.48 103.95 69.13 Cerebellum Clontech 39.33, 37.82 0.74 1.78 1.26 2.17 23.04 29.03 Cervix 36.12, 36.58 4.73 3.62 4.18 2.42 20.66 86.26 Colon 35.23, 38.35 7.9 1.31 4.61 2.71 18.45 84.96 Endometrium 35.51, 40 6.73 0 3.37 0.73 68.21 229.54 Esophagus 37.22, 38.18 2.5 1.45 1.98 1.37 36.50 72.08 Heart Clontech 40, 40 0 0 0.00 1.32 37.88 10.00 Hypothalamus 40, 40 0 0 0.00 0.32 155.28 0.00 Ileum 34.65, 34.11 11.04 15.09 13.07 2.58 19.38 253.20 Jejunum 34.84, 34.04 9.91 15.72 12.82 6.60 7.58 97.08 Kidney 38.2, 39.11 1.43 0.84 1.14 2.12 23.58 26.77 Liver 34.47, 38.59 12.26 1.14 6.70 1.50 33.33 223.33 Fetal Liver Clontech 33.51, 33.07 21.26 27.43 24.35 10.40 4.81 117.04 Lung 27.32, 37.11 755.31 2.68 379.00 2.57 19.46 7373.44 Mammary Gland 36.31, 36.4 4.24 4.03 4.14 13.00 3.85 15.90 Clontech Myometrium 40, 38.7 0.7 1.07 0.89 2.34 21.37 18.91 Omentum 35.44, 36.14 6.98 4.68 5.83 3.94 12.69 73.98 Ovary 38.76, 35.49 1.03 6.82 3.93 4.34 11.52 45.22 Pancreas 40, 38.56 0.48 1.16 0.82 0.81 61.80 50.68 Head of Pancreas 40,40 0 0 0.00 1.57 31.85 0.00 Parotid Gland 36.8, 35.45 3.2 6.98 5.09 5.48 9.12 46.44 Placenta Clontech 35.63, 35.11 6.27 8.47 7.37 5.26. 9.51 70.06 Prostate 37.4, 37.5 2.26 2.14 2.20 3.00 16.67 36.67 Rectum 35.45, 35.25 6.94 7.81 7.38 1.23 40.65 299.80 Salivary Gland 37.3, 37.06 2.4 2.75 2.58 7.31 6.84 17.61 Clontech Skeletal Muscle 40, 39.34 0 0.74 0.37 1.26 39.68 14.68 Clontech Skin 38.84,34.56 0.98 11.63 6.31 1.21 41.32 260.54 Small Intestine 40, 40 0 0.63 0.32 0.98 51.07 16.09 Clontech Spleen 34.37,34.89 13 9.6 11.30 4.92 10.16 114.84 Stomach 39.73, 35.52 0.59 6.67 3.63 2.73 18.32 66.48 Testis Clontech 38.91,40 0.94 0 0.47 0.57 87.87 41.30 Thymus Clontech 31.96, 32.96 52.16 29.2 40.68 9.89 5.06 205.66 Thyroid 35.53, 40 6.66 0 3.33 2.77 18.05 60.11 Trachea Clontech 37.99,37.69 1.61 1.91 1.76 9.71 5.15 9.06 Urinary Bladder 39.69, 39.02 0.6 0.89 0.75 5.47 9.14 6.81 Uterus 34.41, 33.56 12.67 20.75 16.71 5.34 9.36 156.46 genomic 26.31 1359.1 b-actin 27.2 812.88 l.00E+05 19.24 100000 1.00E+05 19.38 100000 L.OOE04 22.67 10000 1.OOE+04 22.67 10000 1.OOE+03 26.31 1000 1.00E+03 26.28 1000 1.OOE+02 30.17 100 1.OOE+02 31.02 100 1.OOE+01 36.17 1.OOE+01 34.46 1.OOE-00 40 0 1.OOE-00 40 1 NTC 40 -1 NTC 40 -1 Sample Reg Ct Mean copies Sample Fold sbgO1l6995IGBrecpt number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populati total on

RNA

colon normal GW98-167 21941 29.45 174.86 349.72 colon normal colon tumor GW98-166 21940 32.1 33.44 66.88 colon tumor -5.23 colon normal GW98-178 22080 31.77 41.07 82.14 colon normal colon tumor GW98-177 22060 32.66 23.5 47.00 colon tumor -1.75 colon normal GW98-561 23514 29.15 211.24 422.48 colon normal colon tumor GW98-560 23513 31.25 56.95 113.90 colon tumor -3.71 colon normal GW98-894 24691 30.68 81.3 162.60 colon normal colon tumor GW98-893 24690 31.33 54.12 108.24 colon tumor -1.50 lung normal GW98-3 20742 31.86 38.92 77.84 lung normal lung tumor GW98-2 20741 34.55 7.25 14.50 lung tumor -5.37 lung normal GW97-179 20677 28.38 342.07 684.14 lung normal lung tumor GW97-178 20676 32.1 33.52 67.04 lung tumor -10.20 lung normal GW98-165 21922 32.2 31.46 62.92 lung normal lung tumor GW98-164 21921 30.5 90.8 181.60 lung tumor 2.89 lung normal GW98-282 22584 29.82 138.8 277.60 lung normal lung tumor GW98-281 22583 32.72 22.64 45.28 lung tumor -6.13 breast normal GWOO-392 28750 31.5 48.65 148.65 breast normal breast tumor GWOO-391 28746 31.9 37.84 75.68 breast tumor 1.56 breast normal GWOO-413 28798 34.37 8.07 8.07 breast normal breast tumor GWO0-412 28797 29.97 126.73 253.46 breast tumor 31.41 breast normal GW0O 27592-95 35.08 5.2 5.20 breast normal breast tumor GWOO- 27588-91 32.3 29.54 29.54 breast tumor 5.68 breast normal GW98-621 23656 31.11 61.96 123.92 breast normal breast tumor GW98-620 23655 31.27 56.22 112.44 breast tumor -1.10 brain normal BB99-542 25507 33.3 15.82 31.64 brain normal brain normal BB99-406 25509 33.02 18.83 37.66 brain normal brain normal BB99-904 25546 33.93 10.62 21.24 brain normal brain stage 5 ALZ BB99- 25502 32.36 28.38 56.76 brain stage 5 ALZ 1.88 brain stage 5 ALZ BB99- 25503 31.79 40.66 81.32 brain stage 5 ALZ 2.69 brain stage 5 ALZ BB99- 25504 32.04 34.76 69.52 brain stage 5 ALZ 2.30 862 brain stage 5 ALZ BB99- 25542 31.79 40.51 81.02 brain stage 5 ALZ 2.68 927 CT lung normal 33.32 15.63 31.26 CT lung Nml lung 26 normal 29.8 140.4 lung 26 Nml lung 27 normal 38.71 0.54 0.54 lung 27 Nml lung 24 COPD 39.31 0.37 0.37 lung 24 COPD -29.00 lung 28 COPD 37.09 1.48 1.48 lung 28 COPD -7.25 lung 23 COPD 38.02 0.83 0.83 lung 23 COPD -12.93 lung 25 normal 39.22 0.39 0.39 lung 25 Nml asthmatic lung OD03112 29321 37.96 0.86 0.86 asthmatic lung -12.48 asthmatic lung OD03433 29323 31.15 60.54 121.08 asthmatic lung 11.28 asthmatic lung OD03397 29322 33.74 12.01 24.02 asthmatic lung 2.24 asthmatic lung OD04928 29325 31.59 46.09 92.18 asthmatic lung 8.59 endo cells control 36.98 1.58 1.58 endo cells____ endo VEGF 39.28 0.38 0.38 endo VEGF -4.16 endo bFGF 37.3 1.3 1.30 endo bFGF -1.22 heart Clontech normal 35.73 3.45 6.90 heart heart (T-1 )ischemic 29417 34.7 6.58 13.16 heart T-l) 1.91 ischemic heart (T-14) non- 29422 37.5 1.15 2.30 heart (T-14) non- -3.00 obstructive DCM ____obstructive DCM heart (T-3399) DCM 29426 35.15 4.96 9.92 heart (T-3399) 1.44 adenoid GW99-269 26162 25.98 1528.07 3056.14 adenoid tonsil GW98-280 22582 24.6 3626.43 7252.86 tonsil T cells PC00314 28453 34.49 7.5 15.00 T cells PBMNC 37.58 1.09 1.09 PBMNC monocyte 37.4 1.22 2.44 monocyte B cells PC00665 28455 31.68 43.59 87.18 B cells dendritic cells 28441 35.05 5.28 10.56 dendritic cells neutrophils 28440 35.68 3.57 3.57 neutrophils eosinophils 28446 35.07 5.23 10.46 eosinophils BM unstim 38.19 0.75 0.75 BM unstim BM stim treated 34.27 8.61 8.61 BM stim 11.48 osteo dif treated 40 0.09 0.09 osteo dif -5.78 osteo undif 40 0.52 0.52 osteo undif chondrocytes 32.86 20.79 51.98 chondrocytes OA Synovium P12/01 29462 31.85 38.99 38.99 OA Synovium OA Synovium NP10/01 29461 34.76 6.33 12.66 OA Synovium OA Synovium NP57/00 28464 31.39 51.96 103.92 OA Synovium RA Synovium NP03/01 28466 31.1 62.3 124.60 RA Synovium RA Synovium NP71/00 28467 31.95 36.76 73.52 RA Synovium RA Synovium NP45/00 28475 32.43 27.14 54.28 RA Synovium OA bone (biobank) 29217 35.84 3.22 3.22 OA bone (biobank) OA bone Sample 1 J. Emory 35.43 4.18 8.36 OA bone OA bone Sample 2 J. Emory 34.86 5.95 11.90 OA bone Cartilage (pool) Normal 34.79 6.21 12.42 Nml Cartilage (pool) Cartilage (pool) OA 36.55 2.07 4.14 OA Cartilage -3.00 (pool) PBL unifected 28441 30.02 122.76 245.52 PBL unifected PBL HIV IB 28442 28.17 388.59 777.18 PBL HIV IIIB 3.17 uninfected 29158 34.6 7.01 14.02 MRC5 uninfected (100%) (100%) HSV strain F 29178 33.27 16.13 32.26 MRCS HSV strain 2.30

F

W12 cells 29179 34.43 7.8 15.60 W12 cells Keratinocytes 29180 35.04 5.31 10.62 Keratinocytes B-actin control 27 808.77 genomic 26.18 1353.11 1.00E+05 19.37 100000 1.00E+05 19.59 100000 .OOE+04 22.75 10000 1.00E+04 22.8 10000 1.00E+03 26.43 1000 1.00E+03 26.17 1000 1.00E+02 30.09 100 1.00E+02 30.21 100 1.00E+01 35.27 1.00E+01 35.55 1.00E-00 39.31 I 1.00E-00 34.53 1 NTC 40 -1 *lung 26 Normal has been omitted due to multiple amplification failures from that sample Gene Name sbgl016995IGBrecpt Disease tissues Fold Change in Disease Population Relative to Normal colon tumor -5.23 colon tumor -1.75 colon tumor -3.71 colon tumor -1.50

IND

N

k,

O

In \o

C,

In o", ot

(N

lung tumor -5.37 lung tumor -10.20 lung tumor 2.89 lung tumor -6.13 breast tumor 1.56 breast tumor 31.41 breast tumor 5.68 breast tumor -1.10 brain stage 5 ALZ 1.88 brain stage 5 ALZ 2.69 brain stage 5 ALZ 2.30 brain stage 5 ALZ 2.68 lung 24 -29.00 lung 28 -7.25 lung 23 -12.93 asthmatic lung -12.48 asthmatic lung 11.28 asthmatic lung 2.24 asthmatic lung 8.59 endo VEGF -4.16 endo bFGF -1.22 heart T-1 1.91 heart T-14 -3.00 heart T-3399 1.44 BM stim 11.48 osteo dif -5.78 Cartilage (pool) -3.00 PBL HIV IB 3.17 HSV strain F 2.30 Gene Name sbg 15 1bSREC Highest overall expression in normal and disease samples. Fairly ubiquitously expressed but highest normal expression in adipocytes, adipose, whole brain, fetal brain, and endometrium.

Highest disease expression in one of the colon tumor samples, one of the normal lung samples, chondrocytes, and the uninfected MRC5. There are no significant changes in brains from patients with Alzheimer's disease. Downregulation in 1 of 4 lung tumors suggests possible implication in lung cancer. Upregulation in 1 of 4 breast tumor samples is sufficient to claim a role in cancer of the breast. Upregulation in 1 of 4 asthma lungs implies a role in asthma. Downregulation in HSV implicates involvement in herpes simplex virus as a potential host factor. High expression in immune cells. High expression in cartilage and bone samples from patients with OA as well as high expression in chondrocytes possible involvement in osteoarthritis and rheumatoid arthritis.

Additionally, the corroborating expression in immune cells (particularly B and T cells) provides additional evidence for a role in RA/OA.

Sample Ct (sample Mean Mean Average 18S 50 copies of 1 and 2) GOI GOI GOI rRNA ng/18S mRNA copies copies Copies (ng) rRNA detected (sample (sample (ng) /50 ng 1) 2) total

RNA

Subcutaneous 28.31, 28.35 477.04 466.02 471.53 3.06 16.34 7704.74 Adipocytes Zenbio Subcutaneous Adipose 30.79,30.22 122.3 166.95 144.63 0.96 52.36 7571.99 Zenbio Adrenal Gland Clontech 33.96, 33.47 21.39 27.97 24.68 0.61 81.97 2022.95 Whole Brain Clontech 24.07, 23.98 4889.28 5123.8 5006.54 7.24 6.91 34575.55 Fetal Brain Clontech 31.1,32.29 103.16 53.55 78.36 0.48 103.95 18145.01 Cerebellum Clontech 31.03, 31.99 107.02 63.18 85.10 2.17 23.04 1960.83 Cervix 31.22, 30.06 96.6 182.64 139.62 2.42 20.66 2884.71 Colon 30.68, 30.53 129.52 140.99 135.26 2.71 18.45 2495.48 Endometrium 30.59, 30.44 136.06 147.8 141.93 0.73 68.21 9681.45 Esophagus 33.11, 32.17 34.08 57.32 45.70 1.37 36.50 1667.88 Heart Clontech 33.19, 32.41 32.68 50.11 41.40 1.32 37.88 1567.99 Hypothalamus 34.34, 40 17.4 0 8.70 0.32 155.28 1350.93 Ileum 31.29, 30.13 92.84 174.99 133.92 2.58 19.38 2595.25 Jejunum 29.7,29.48 221.9 251.05 236.48 6.60 7.58 1791.48 Kidney 31.03, 30.17 107.15 171.45 139.30 2.12 23.58 3285.38 Liver 32.89, 33.16 38.61 33.17 35.89 1.50 33.33 1196.33 Fetal Liver Clontech 28.05, 28.15 550.64 518.95 534.80 10.40 4.81 2571.13 Lung 29.39, 28.63 263.85 398.99 331,42 2.57 19.46 6447.86 Mammary Gland 27.56, 27.39 717.67 789.94 753.81 13.00 3.85 2899.25 Clontech Myometrium 29.08, 28.93 312.86 339.46 326.16 2.34 21.37 6969.23 Omentum 30.72, 29.32 126.7 273.04 199.87 3.94 12.69 2536.42 Ovary 28.89, 28.68 346.91 388.02 367.47 4.34 11.52 4233.47 Pancreas 35.24, 35.75 10.59 8.02 9.31 0.81 61.80 575.09 Head of Pancreas 35.25, 33.21 10.57 32.34 21.46 1.57 31.85 683.28 Parotid Gland 28.46, 27.84 438.62 615.36 526.99 5.48 9.12 4808.30 Placenta Clontech 28.67, 28.66 391.9 393.15 392.53 5.26 9.51 3731.23 Prostate 30.55, 31.46 139.05 84.64 111.85 3.00 16.67 1864.08 Rectum 31.28, 31.43 93.33 85.92 89.63 1.23 40.65 3643.29 Salivary Gland 31.13, 30.57 101.46 138.16 119.81 7.31 6.84 819.49 Clontech

I

Skeletal Muscle 34.05, 35.24 20.38 10.59 15.49 1.26 39.68 614.48 Clontech Skin 31.53, 31.2 81.49 97.36 89.43 1.21 41.32 3695.25 Small Intestine 34.81, 33.82 13.41 23.18 18.30 0.98 51.07 934.37 Clontech Spleen 31.01, 30.44 108.41 147.9 128.16 4.92 10.16 1302.39 Stomach 32.01, 31.1 62.6 102.97 82.79 2.73 18.32 1516.21 Testis Clontech 31.74, 32.29 72.49 53.45 62.97 0.57 87.87 5533.39 Thymus Clontech 28.84, 28.53 356.64 421.44 389.04 9.89 5.06 1966.84 Thyroid 30.12, 30.04 176.76 184.5 180.63 2.77 18.05 3260.47 Trachea Clontech 28.48, 28.38 434.3 459.42 446.86 9.71 5.15 2301.03 Urinary Bladder 29.63, 29.55 230.25 241.15 235.70 5.47 9.14 2154.48 Uterus 28.69, 28.37 387.47 461.07 424.27 5.34 9.36 3972.57 genomic 26.24 1487.44 b-actin 27.28 839.2 1.00E+05 18.96 100000 1.OOE+05 19.34 100000 1.00E+04 22.64 10000 1.00E+04 22.84 10000 1.00E+03 26.22 1000 1.00E+03 26.04 1000 1.00E+02 31.04 100 1.00E+02 30.1 100 1.OOE+01 33.33 1.OOE+01 39.08 1.OOE-00 40 0 L.OOE-00 40 1 NTC 40 0 NTC 40 0 Sample Reg Ct Mean copies of Sample Fold sbg115lbSREC number GOI mRNA Change (GSK copies detected in Disease identifie /50 ng Populatio r) total n

RNA

colon normal GW98-167 21941 24.55 5357.25 10714.50 colon normal colon tumor GW98-166 21940 22.61 19769.94 39539.88 colon tumor 3.69 colon normal GW98-178 22080 26.71 1252.3 2504.60 colon normal colon tumor GW98-177 22060 26.13 1854.49 3708.98 colon tumor 1.48 colon normal GW99-561 23514 26.82 1165.06 2330.12 colon normal colon tumor GW98-560 23513 25.75 2390.26 4780.52 colon tumor 2.05 colon normal GW98-894 24691 26.06 1948.57 3897.14 colon normal colon tumor GW98-893 24690 26.59 1362.55 2725.10 colon tumor -1.43 lung normal GW98-3 20742 22.77 17753 35506.00 lung normal lung tumor GW98-2 20741 26.17 1803.8 3607.60 lung tumor -9.84 lung normal GW97-179 20677 25.24 3370.88 6741.76 lung normal lung tumor GW97-178 20676 24.14 7057.92 14115.84 lung tumor 2.09 lung normal GW98-165 21922 23.87 8442.49 16884.98 lung normal lung tumor GW98-164 21921 24.08 7339.83 14679.66 lung tumor -1.15 lung normal GW98-282 22584 25.51 2804.42 5608.84 lung normal lung tumor GW98-281 22583 24.2 6787.31 13574.62 lung tumor 2.42 breast normal GWOO-392 28750 25.7 2480.5 2480.50 breast normal breast tumor GWOO-391 28746 25.77 2364.2 4728.40 breast tumor 1.91 breast normal GWOO-413 28798 26.06 1948.1 1948.10 breast normal breast tumor GWOO-412 28797 27.21 894.11 1788.22 breast tumor -1.09 breast normal GWOO- 27592-95 26.64 1317.83 1317.83 breast normal 235:238 breast tumor GWOO- 27588-91 23.91 8225.11 8225.11 breast tumor 6.24 231:234 breast normal GW98-621 23656 24.46 5693.73 11387.46 breast normal breast tumor GW98-620 23655 23.91 8218.73 16437.46 breast tumor 1.44 brain normal BB99-542 25507 26.39 1553.13 3106.26 brain normal brain normal BB99-406 25509 26.63 1325.63 2651.26 brain normal brain normal BB99-904 25546 27.05 1001.6 2003.20 brain normal brain stage 5 ALZ BB99- 25502 26.97 1052.15 2104.30 brain stage 5 ALZ -1.23 874 brain stage 5 ALZ BB99- 25503 25.28 3289.99 6579.98 brain stage 5 ALZ 2.54 887 brain stage 5 ALZ BB99- 25504 26.24 1725.06 3450.12 brain stage 5 ALZ 1.33 862 r brain stage5 ALZBB99- 25542 26.12 1864.26 3728.52 brain stage 5 ALZ 1.44 927 CT lung KC normal 24.74 4711.99 9423.98 CT lung lung 26 KC normal 27.78 611.36 611.36 lung 26 lung 27 KC normal 28.27 439.19 439.19 lung 27 lung24 KC COPD 26.92 1091.11 1091.11 lung24 -2.56 lung 28 KC COPD 26.93 1085.65 1085.65 lung 28 -2.57 lung 23 KC COPD 27.19 909.68 909.68 lung 23 -3.07 lung 25 KC normal 27.62 678.79 678.79 lung asthmatic lung OD03112 29321 25.33 3173.52 3173.52 asthmatic lung 1.14 asthmatic lung OD03433 29323 25.36 3106.89 6213.78 asthmatic lung 2.23 asthmatic lung OD03397 29322 23.81 8809.42 17618.84 asthmatic lung 6.32 asthmatic lung OD04928 29325 24.76 4649.98 9299.96 asthmatic lung 3.34 endo cells KC control 26 2021.13 2021.13 endo cells endo VEGF KC 25.78 2343.21 2343.21 endo VEGF 1.16 endo bFGF KC 26.7 1264.03 1264.03 endo bFGF -1.60 heart Clontech normal 26.62 1330.64 2661.28 heart heart (T-1 ischemic 29417 27.07 984.33 1968.66 heart T-1 -1.35 heart (T-14) non- 29422 26.11 1877.75 3755.50 heart T-14 1.41 obstructive DCM heart (T-3399) DCM 29426 26.34 1608.79 3217.58 heart T-3399 1.21 adenoid GW99-269 26162 27.64 670.25 1340.50 adenoid tonsil GW98-280 22582 27.61 684.15 1368.30 tonsil T cells PC00314 28453 25.95 2098.64 4197.28 T cells PBMNC 31.16 63.19 63.19 PBMNC monocyte 31.32 56.63 113.26 monocyte B cells PC00665 28455 26.34 1609.52 3219.04 B cells dendritic cells 28441 28.25 444.68 889.36 dendritic cells neutrophils 28440 26.11 1874.13 1874.13 neutrophils eosinophils 28446 26.39 1553.82 3107.64 eosinophils BM unstim 31.45 51.76 51.76 BM unstim BMstim 31.28 58.37 58.37 BM stim 1.13 osteo dif 24.62 5118.74 5118.74 osteo dif 1.70 osteo undif 25.41 3015.6 3015.60 osteo undif chondrocytes 22.12 27351.89 68379.73 chondrocytes OA Synovium IP12/01 29462 24.5 5551.61 5551.61 OA Synovium OA Synovium NP10/01 29461 25.1 3711.29 7422.58 OA Synovium OA Synovium NP57/00 28464 24.5 5537.1 11074.20 OA Synovium RA Synovium NPO3/01 28466 26.45 1492.95 2985.90 RA Synovium RA Synovium NP71/00 28467 24.44 5783.96 11567.92 RA Synovium RA Synovium NP45/00 28475 25.94 2112.54 4225.08 RA Synovium OA bone (biobank) 29217 26.16 1811.72 1811.72 OA bone (biobank) OA bone Sample 1 J. Emory 24.54 5399.31 10798.62 OA bone OA bone Sample 2 J. Emory 26.07 1931.94 3863.88 OA bone Cartilage (pool) Normal 25.09 3730.42 7460.84 Cartilage (pool) Cartilage (pool) OA 25.79 2328.66 4657.32 Cartilage (pool) -1.60 PBL unifected 28441 26.95 1068.16 2136.32 PBL unifected PBL HIV IIIB 28442 28.41 401.86 803.72 PBL HIV I[B -2.66 uninfected 29158 22.28 24694.87 49389.74 MRC5 uninfected (100%) HSV strain F 29178 29.07 256.64 513.28 MRC5 HSV strain -96.22

F

W12 cells 29179 28.37 410.68 821.36 W12 cells Keratinocytes 29180 29.12 249.25 498.50 Keratinocytes B-actin control 27.53 721.15 genomic 26.92 1091.74 1.OOE+05 19.96 100000 1.00E+05 20.19 100000 1.00E+04 23.43 10000 1.00E+04 23.34 10000 1.00E+03 26.64 1000 1.00E+03 26.8 1000 1.00E+02 31.34 100 1.00E+02 31.48 100 1.00E+01 34.9 1OOE+01 34.19 1.00E-00 40 0 1.00E-00 35.53 1 NTC 40 0 Gene Name sbgl 151bSREC Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 3.69 colon tumor 1.48 colon tumor 2.05 colon tumor -1.43 lung tumor -9.84 lung tumor 2.09 lung tumor -1.15 lung tumor 2.42 breast tumor 1.91 breast tumor -1.09 breast tumor 6.24 breast tumor 1.44 brain stage 5 ALZ -1.23 brain stage 5 ALZ 2.54 brain stage 5 ALZ 1.33 brain stage 5 ALZ 1.44 lung 24 -2.56 lung 28 -2.57 lung 23 -3.07 asthmatic lung 1.14 asthmatic lung 2.23 asthmatic lung 6.32 asthmatic lung 3.34 endo VEGF 1.16 endo bFGF -1.60 heart T-1 -1.35 heart T-14 .1.41 heart T-3399 1.21 BM stim 1.13 osteo dif 1.70 Cartilage (pool) -1.60_ PBL HIV flB -2.66 HSV strain F -96.22 Gene Name sbg1399854ANK Low overall expression. Highest normal expression is seen in the whole brain, fetal brain, and liver.

Good levels of expression are seen in all of the samples representing the female reproductive system. Highest disease expression is seen in the normal and Alzheimer's brain samples as well as in the dendritic cells. Upregulation in 2 of 4 colon tumor samples and in 2 of 4 breast tumor samples as well as downregulation in 2 of 4 lung tumor samples implicates this gene in cancers of the colon, breast, and lung. Downregulation in 3 of 3 COPD samples and in 2 of 4 asthmatic lung samples suggests a potential role for this gene in chronic obstructive pulmonary disorder and asthma. Downregulation in the OA cartilage sample as well as corroborating low expression in the normal chondrocytes and many of the immune cells suggests involvement in osteoarthritis.

Upregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV.

Sample Ct (sample Mean Mean Average 18S 50 copies sbgl399854ANK 1 and 2) GOI GOI GOI rRNA ng/18S of copies copies Copies (ng) rRNA mRNA (sample (sample (ng) detecte 1) 2) d/50 ng total Subcutaneous 40,40 0 0 0.00 3.06 16.34 0.00 Adipocytes Zenbio____ Subcutaneous Adipose 40,40 1.83 1.77 1.80 0.96 52.36 94.24 Zenbio Adrenal Gland Clontech 40,40 1.75 0 0.88 0.61 81.97 71.72 Whole Brain Clontech 28.57,28.35 944.29 1058.09 1001.19 7.24 6.91 6914.30 Fetal Brain Clontech 36.57, 34.65 14.38 39.28 26.83 0.48 103.95 2788.98 Cerebellum Clontech 37.21, 36.71 10.3 13.37 11.84 2.17 23.04 272.70 Cervix 36.3,40 16.52 0 8.26 2.42 20.66 170.66 Colon 36.17,35.71 17.73 22.5 20.12 2.71 18.45 371.13 Endometrium 40, 36.1 0 18.41 9.21 0.73 68.21 627.90 Esophagus 40,40 0 1.58 0.79 1.37 36.50 28.83 Heart Clontech 40, 40 0 0 0.00 1.32 37.88 0.00 Hypothalamus 40, 40 0 0 0.00 0.32 155.28 0.00 Ileum 40, 40 0 0 0.00 2.58 19.38 0.00 Jejunum 34.07,34.37 53.18 45.33 49.26 6.60 7.58 373.14 Kidney 37.55, 40 8.58 0 4.29 2.12 23.58 101.18 Liver 36.53,35.62 14.69 23.59 19.14 1.50 33.33 638.00 Fetal Liver Clontech 34.56, 34.61 41.04 40.04 40.54 10.40 4.81 194.90 Lung 40,40 0 0 0.00 2.57 19.46 0.00 Mammary Gland 39.07, 39.45 3.89 3.18 3.54 13.00 3.85 13.60 Clontech____ Myometrium 39.5,35.37 3.1 26.93 15.02 2.34 21.37 320.83 Omentum 40,36.18 0 17.61 8.81 3.94 12.69 111.74 Ovary 35.87,34.34 20.75 46.22 33.49 4.34 11.52 385.77 Pancreas 40,40 0 0 0.00 0.81 61.80 0.00 Head of Pancreas 40,39.79 0 2.66 1.33 1.57 31.85 42.36 Parotid Gland 35.2,38.6 29.46 4.97 17.22 5.48 9.12 157.07 Placenta Clontech 40,38.14 0 6.32 3.16 5.26 9.51 30.04 Prostate 40,40 0 0 0.00 3.00 16.67 0.00 Rectum 40,39.2 0 3.63 1.82 1.23 40.65 73.78 Salivary Gland 40,39.19 2.19 3.64 2.92 7.31 6.84 19.94 Skeletal Muscle 40,39.37 0 3.32 1.66 1.26 39.68 65.87 Clontech Skin 40,40 0 2.09 1.05 1.21 41.32 43.18 Small Intestine 40, 40 1.44 0 0.72 0.98 51.07 36.77 Clontech____ Spleen 35.36,40 27.05 1.84 14.45 4.92 10.16 146.80 Stomach 40,37.03 1.93 11.29 6.61 2.73 18.32 121.06 Testis Clontech 40, 37.99 0 6.82 3.41 0.57 87.87 299.65 Thymus Clontech 38.47, 35.55 5.32 24.52 14.92 9.89 5.06 75.43 Thyroid 40,40 0 2.15 1.08 2.77 18.05 19.40 Trachea Clontech 35.37, 36.67 26.97 13.66 20.32 9.71 5.15 104.61 Urinary Bladder 39.07, 40 3.89 1.42 2.66 5.47 9.14 24.27 Uterus 36.01, 33.41 19.29 75.06 47.18 5.34 9.36 441.71 genomic 29.57 558.84 b-actin 27.57 1.00E+05 19.91 100000____ 1.00E+05 20.08 100000____ 1.00E+04 23.79 10000 1.00E+04 24.06 10000 1.00E+03 27.72 1.00E+03 28.29 1.00E+02 31.95 1.00E+02 33.62 100____ 1.00E+01 39.75 1.00E+01 35.41 1.00E-00 40 1.00E-00 40 NTC 40 -1 NTC 40 Sample Reg Ct Mean copies Sample Fold sbg1399854ANK number GOI of Change (GSK copies mRNA in identifier detecte Disease d/50 ng Populati total on colon normal GW98-167 21941 35.32 22.34 44.68 colon normal colon tumor GW98-166 21940 34.14 47.5 95.00 colon tumor 2.13 colon normal GW98-178 22080 36.16 13.07 26.14 colon normal colon tumor GW98-177 22060 35.58 18.93 37.86 colon tumor 1.45 colon normal GW98-561 23514 36.58 10.03 20.06 colon normal colon tumor GW98-560 23513 32.61 126.48 252.96 colon tumor 12.61 colon normal GW98-894 24691 35.61 18.62 37.24 colon normal colon tumor GW98-893 24690 33.24 84.75 169.50 colon tumor 4.55 lung normal GW98-3 20742 34.77 31.8 63.60 lung normal lung tumor GW98-2 20741 33.63 66.03 132.06 lung tumor 2.08 lung normal GW97-179 20677 34.76 32.04 64.08 lung normal lung tumor GW97-178 20676 34.44 39.23 78.46 lung tumor 1.22 lung normal GW98-165 21922 35.18 24.44 48.88 lung normal lung tumor GW98-164 21921 37.99 4.06 8.12 lung tumor -6.02 lung normal GW98-282 22584 33.64 65.37 130.74 lung normal lung tumor GW98-281 22583 37.3 6.34 12.68 lung tumor -10.31 breast normal GWOO-392 28750 36.29 12.08 12.08 breast normal breast tumor GWOO-391 28746 36.14 13.29 26.58 breast tumor 2.20 breast normal GWOO-413 28798 37.08 7.29 7.29 breast normal breast tumor GWOO-412 28797 33.26 83.58 167.16 breast tumor 22.93 breast normal GWOO- 27592-95 38.93 2.24 2.24 breast normal 235:238 breast tumor GWOO- 27588-91 36.57 10.08 10.08 breast tumor 4.50 231:234 breast normal GW98-621 23656 34.9 29.32 58.64 breast normal breast tumor GW98-620 23655 36.11 13.51 27.02 breast tumor -2.17 brain normal BB99-542 25507 29.6 866.9 1733.80 brain normal brain normal BB99-406 25509 31.93 194.87 389.74 brain normal brain normal BB99-904 25546 30.38 526.58 1053.16 brain normal brain stage 5 ALZ BB99- 25502 32.7 119.57 239.14 brain stage 5 ALZ -4.43.

874 brain stage 5 ALZ BB99- 25503 30.08 634.97 1269.94 brain stage 5 ALZ 1.20 887 brain stage 5 ALZ BB99- 25504 29.7 809.22 1618.44 brain stage 5 ALZ 1.53 862 brain stage 5 ALZ BB99- 25542 29.93 700.82 1401.64 brain stage 5 ALZ 1.32 927 CT lung normal 35.1 25.82 51.64 CT lung Nml lung 26 normal 36.74 9.07 lung 26 Nml lung 27 normal 40 0 10.00 lung 27 Nml lung 24 COPD 40 2.5 2.50 lung 24 COPD -7.11 lung 28 COPD 40 0 0.00 lung 28 COPD -17.77 lung 23 COPD 40 0 0.00 lung 23 COPD -17.77 lung 25 normal 39.39 1.67 1.67 lung 25 Nml asthmatic lung OD03112 29321 40 0 0.00 asthmatic lung -17.77 asthmatic lung OD03433 29323 37 7.68 15.36 asthmatic lung -1.16 asthmatic lung OD03397 29322 36.08 13.8 27.60 asthmatic lung 1.55 asthmatic lung OD04928 29325 40 0 0.00 asthmatic lung -17.77 endo cells control 40 0 0.00 endo cells endo VEGF 40 0 0.00 endo VEGF 0.00 endo bFGF 35.68 17.77 17.77 endo bFGF 17.77 heart Clontech normal 35.03 26.95 53.90 heart heart (T-1 ischemic 29417 36.36 11.53 23.06 heart T- -2.34 I ischemic heart (T-14) non- 29422 34.57 36.11 72.22 heart (T-14) non- 1.34 obstructive DCM obstructive DCM heart (T-3399) DCM 29426 36.25 12.37 24.74 heart (T-3399) -2.18

DCM

adenoid GW99-269 26162 38.51 2.92 5.84 adenoid tonsil GW98-280 22582 35.05 26.54 53.08 tonsil T cells PC00314 28453 35.5 19.98 39.96 T cells PBMNC 40 0 0.00 PBMNC monocyte 40 0 0.00 monocyte B cells PC00665 28455 33.78 59.82 119.64 B cells dendritic cells 28441 29.33 1026.14 2052.28 dendritic cells neutrophils 28440 31.3 292.56 292.56 neutrophils eosinophils 28446 35.97 14.79 29.58 eosinophils BM unstim 35.56 19.16 19.16 BM unstim BM stim treated 34.79 31.48 31.48 BM stim 1.64 osteo dif treated 40 2.59 2.59 osteo dif 2.59 osteo undif 40 0 0.00 osteo undif chondrocytes 37.11 7.15 17.88 chondrocytes OA Synovium 1P12/01 29462 35.95 14.93 14.93 OA Synovium OA Synovium NP10/01 29461 35.74 17.17 34.34 OA Synovium OA Synovium NP57/00 28464 39.09 2.02 4.04 OA Synovium RA Synovium NPO3/01 28466 38.03 3.97 7.94 RA Synovium RA Synovium NP71/00 28467 35.08 26.03 52.06 RA Synovium RA Synovium NP45/00 28475 37.11 7.13 14.26 RA Synovium OA bone (biobank) 29217 33.76 60.54 60.54 OA bone (biobank) OA bone Sample 1 J. Emory 33.35 78.68 157.36 OA bone OA bone Sample 2 J. Emory 34.15 47.2 94.40 OA bone Cartilage (pool) Normal 35.05 26.63 53.26 Nml Cartilage Cartilage (pool) OA 37.42 5.87 11.74 OA Cartilage -4.54 1 (pool) PBL unifected 28441 33.95 53.63 107.26 PBL unifected PBL HIV IIIB 28442 33.3 81.2 162.40 PBL HV IIB 1.51 uninfected 29158 39.41 1.64 3.28 MRC5 uninfected (100%) (100%) HSV strain F 29178 35.73 17.22 34.44 MRC5 HSV strain 10.50

F

W12 cells 29179 35.08 26.08 52.16 W12 cells Keratinocytes 29180 36.69 9.33 18.66 Keratinocytes B-actin control 28.13 2213.67 genomic 29.03 1240.79 1.00E+05 22.03 100000 1.00E+05 22.36 100000 1.00E+04 25.68 10000 1.00E+04 25.78 10000 1.00E+03 29.01 1000 1.00E+03 28.67 1000 1.00E+02 33.46 100 1.00E+02 140 100 1.00E+0l 38.75 10 l.00E+01 40 10 1.OOE-00 40 0 1.00E-00 1 NTC 0 *luncy 26 Normal has been omitted due to multiple amplification failures from that sample Gene Name sbgl399854ANX Disease tissues Fold Change in Disease Population Relative to Normal colon tumor 2.13 colon tumor 1.45 colon tumor 12.61 colon tumor 4.55 lung tumor 2.08 lung tumor 1.22 lung tumor -6.02 lung tumor -10.31 breast tumor 2.20 breast tumor 22.93 breast tumor 4.50 breast tumor -2.17 brain stage 5 ALZ -4.43 brain stage 5 ALZ 1.20 brain stage 5ALZ 1.53 brain stage 5 ALZ 1.32 lung 24 7.11 lung 28 17.77 lung 23 -17.77 asthmatic lung -17.77 asthmatic lung -1.16 asthmatic lung 1.55 asthmatic lung -17.77 endo VEGF 0.00 endo bFGF 17.77 heart T- 1 -2.34 heart T- 14 1.34 heart T-3399 -2.18 BM stim 1.64 osteo dif 2.59 Cartilage (pool) -4.54 PBL HVIIIB 1.51 HSV strain F 10.50 Table V. Additional diseases based on mRNA expression in specific tissues Tissue Additional Diseases Expression Brain Neurological and psychiatric diseases, including Alzheimers, parasupranuclear palsey, Huntington's disease, myotonic dystrophy, anorexia, depression, schizophrenia, headache, amnesias, anxiety disorders, sleep disorders, multiple sclerosis Heart Cardiovascular diseases, including congestive heart failure, dilated cardiomyopathy, cardiac arrhythmias, Hodgson's Disease, myocardial infarction, cardiac arrhythmias Lung Respiratory diseases, including asthma, Chronic Obstructive Pulmonary Disease, cystic fibrosis, acute bronchitis, adult respiratory distress syndrome Liver Dyslipidemia, hypercholesterolemia, hypertriglyceridemia, cirrhosis, hepatic encephalopathy, fatty hepatocirrhosis, viral and nonviral hepatitis, Type II Diabetes Mellitis, impaired glucose tolerance Kidney Renal diseases, including acute and chronic renal failure, acute tubular necrosis, cystinuria, Fanconi's Syndrome, glomerulonephritis, renal cell carcinoma, renovascular hypertension Skeletal Eulenburg's Disease, hypoglycemia, obesity, tendinitis, periodic paralyses, muscle malignant hyperthermia, paramyotonia congenita, myotonia congenita Intestine Gastrointestinal diseases, including Myotonia congenita, Ileus, Intestinal Obstruction, Tropical Sprue, Pseudomembranous Enterocolitis Spleen/lymph Lymphangiectasia, hypersplenism, angiomas, ankylosing spondylitis, Hodgkin's Disease, macroglobulinemia, malignant lymphomas, rheumatoid arthritis Placenta Choriocarcinoma, hydatidiform mole, placenta previa Testis Testicular cancer, male reproductive diseases, including low testosterone and male infertility Pancreas Diabetic ketoacidosis, Type 1 2 diabetes, obesity, impaired glucose tolerance

Claims (5)

1. 3. An expression vector comprising a polynucleotide capable of producing a polypeptide of claim 1 when said expression vector is present in a compatible host cell.
2. 4. A process for producing a recombinant host cell which comprises the step of introducing an expression vector comprising a polynucleotide capable of producing a polypeptide of claim 1 into a cell such that the host cell, under appropriate culture conditions, produces said polypeptide. A recombinant host cell produced by the process of claim 4.
3. 6. A membrane of a recombinant host cell of claim 5 expressing said polypeptide.
4. 7. A process for producing a polypeptide which comprises culturing a host cell of claim under conditions sufficient for the production of said polypeptide and recovering said polypeptide from the culture. O O 7. A process for producing a polypeptide which comprises culturing a host cell of claim 0 under conditions sufficient for the production of said polypeptide and recovering said polypeptide from the culture. tn DATED this 26th day of October 2005. In 0 Glaxo Group Limited 0 C SmithKline Beecham p.l.c. SmithKline Beecham Corporation by their Patent Attorneys DAVIES COLLISON CAVE SEQUENCE LISTING <2.10> SMITHKLINE BEECHAM CORPORATION SMITHKLINE BEECHAM p.1. c. GLAXO GROUP, LIMITED <120> NOVEL COMPOUNDS <1120> GP50034 <140> TO BE ASSIGNED <141> 2001-09-13 <150> 60/232,463 <151> 2000-09-13 <150> 60/232,455 <151> 2000-09-13 <150> 60/237,293 <151> 2000-10-02 <150> 60/246,269 <151> 2000-11-07 <150> 60/252,049 <151> 2000-11-20 <160>*88 <170> FastSEQ for Windows Version <210> <211> <212> <213> 1 1707 DNA H-omo sapiens <400> 1 atgaaggaag tccctgcacc aggctcgttc ctctttgtag caagccgtaa caccactttg gagaattcca aattcgcagc gtaaaaggag tccctggagg gctttaactt ctccacgtgc agagccaatg tcccagaccc ttaagaggtc atggtcacag caggtattca aatggtcata gcttcagcct gagatccaga caggagcaga cagagatgga cccaagaggt aggctacccc tgggtaagcc ttctgggaga gcagggaggc gtgcctgggt tccaggtgct t tc taaagga gaaccaatgc tccagacgct taagcagagg ctgagatcca aggcctttat atttggaaag ccc agac cca agtcagagat tgaaaaatgc taacttccca ggttaagagg gtcgcctgaa cggtgaggca ggactctgtg ggcatttatg cccagttcaa caacattact agaaatgcga agtagaaatc cggtgatcat tgccac taca tgagatccag gaatttctta cttagaaaat gggactaaag aaaaagcagt agctggtga~t aaaagcaaat ggaaaatgtg cagcagagag gacccagatg ggatctagag gaccctccat gtccgcttct gcaatggctc gctgtgacct cagcagacaa gggcatttac gagcttatcc cagatgttga ctgggaaaca ttgagtttgc aggctcaagg aaaagcagtt gcaaactctg gaaaatt tgc tt tgacaaca gaaattcacg ggccgtctgg aataccttaa atacaga ccc ttagacagca aacaccaaag gtggtcatta 1179 gcacagataa ctgcagcccc tggtcttctc gacctgttcc cttttgaacc agacatttaa agtgcagagt ccaatgctga agacacagat aagacc ttga tagaaaacac aaattcagat agaacacaaa ctagtgctga tgt taaaaag accagacaga atgcccagat taaaacaagg atctgcagaa ctctaaccat cttcacagga ccagtgtgtc caagataccg tcttgtgact gaagcctgtg caacaatcat aggccacatg ggacaatgtc catccagatg gttaaggagt aaaggcagat cagcattgag gttgaatgcc tgctttaaac gatccagttc ggatttgaaa tactcagatt tcaggtctta aatgaagaat ggccagtgcc ggaaatccag acagctacaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 agaacccaaa ttatattatt cagggagccc acaagtaaag tggacagatg tgggaaaaga caaattcag~c aagcccatgg gtcagcttc.t. ccagatggtc tttctagtgt caagaagtct atctggcatc tgtggcctcc tgtactactg gatcggtctc ggacaccatt caacgccgcc atcagtctga caactggcgg agaagtggaa tgacatgacc gccagggtgt ggcctga ctgcaaggct tggcatgagg aaggaggagc actgacaggg cagaacaaag cacaagaatg tgtgac ac cc ggaagttcaa ctgagcagtt aggcatttct gcacagaggg cccctgttgt ggcagactga cctatcagtg tggtggaagc ctgcgtgtcc ggtagagttc ctcctggcgc cttcgggttt agactgtgtc ggtgtgcaag 1320 1380 1440 1500 1560 1620 1680 1707 <210> 2 <211> 1095 <212> DNA <213> Homo sapiens <400> 2 atgtcgagac ttgccaaagg aatgttgtag gattttccaa caagttccta aaatcctttt aaggaaaatt acgataacac agcaagttct aaatacacca caggggaagt ggactcgcat ctcagaatgt gttcctttcc catctggaag gtgatactgt gagaaaaaca tttcgtgtgt atgaaaacat gtggatacat ccctatcaac atggagtttc aataacatga ttacctgtat actgcatatt gtgggcCCCC tcagtatatc ctccagggtc ggctctgtaa ctgtaacatg ccatgtgtgg tatctgaaga. gatggaaaac tctatgcaaa aaagcgatga tatcatcacc cctatatgtg aatga <210> 3 <211> 984 <212> DNA <213> Homo sapiens attttctgct tcctagcacc aaaggatagt tggatttctg tttctattac aacatgcaca ttttgtgaaa acaaat tatt agaacggggc acctgaactc agtcgaggtg taatggaata tccatctatt aacagtgacg cagaaataaa aaacatgaac aacaggggat accatttcga. tttggagtgg attgcggatg tttgtgttat tatgatgaag tcctgtgaat gaagaaggat aatggtcatt tgcaacacag tggtccactc gagtacggtt aattgcagaa tggacagagc aacaatggag taccgttgc cagtggtcag aaaaataaca gctgttgaat gcaatctgtc gttgttgtgt tgcacaatgg ttttcccagg aagat tataa. ataattttgt ggtcaccaac c tgaatct tc gatacagcct ctcccatatg atgttcagcc atgaatatgc ttcctatgtg ataccacctc agtccttcta aaccaccaag tacagttaaa tccagtgtaa aggaagggaa aacggcaggc ttatacgatg aacactttgt ccctttttcc gtctccttca accgaagtgt aggactaata tcaaaacaat cagcttcact gtctgtccct aatgattgga, tgttgagtct attcccatta taaactccag, atgcc tagat atggagaaac attcccacat atttgaatat 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1095 <400> 3 atgttgctct acactttgtg cctttttccc tctccttcaa ccgaagtgtc ggactaatac caaaacaatg agcttcacta tctgtccctC atgattggaa gttgagtcta ttcccattat aaactccagg tgcc tagatc ttcccacata tattcagtgt attttccaaa. aagttcctac aatccttttg tcagaatgtg atctggaagg agaaaaacat tgaaaacatg cctatcaaca ataacatgat ctgcatattg cagtatatcc gctctgtaac catgtgtggt atggaaaact aagcgatgat aatcctaatc aatacaccat aggggaagtt gactcgcata. ttcctttcct tgatactgta ttcgtgtgta tggatacata, tggagtttca tacctgtatt tgggccccct tccagggtca tgtaacatgc atc tgaagaa. ctatgcaaaa atcatcacca. tcatgggtat ggatttctgt ttctattact acatgcacag tttgtgaaaa caaattattt gaacggggc t cctgaactcg gtcgaggtga aatggaatat ccatctatta. acagtgacgt agaaataaac aacatgaaca acaggggatg ccatttcgag ccactgt tgg atgatgaaga cctgtgaata aagaaggatg atggtcattc. gcaacacagg ggtccactcc agtacggtta attgcagaaa. ggacagagct acaatggaga accgttgcca agtggtcaga aaaataacat ctgttgaatt caatctgtca gggagaagga agattataac taattttgtg gtcacca'aca tgaatcttca atacagcctt tcccatatgc tgttcagccg tgaatatgca. tcctatgtgt taccacctca. gtccttctat accaccaaga. acagttaaaa. ccagtgtaaa ggaagggaaa. 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 984 tttgaatatc ctatatgtga. atga 2f79 <210> 4 <211> 465 <212> DNA <213> Homo sapiens <400> 4 atggcaccgg gcagaggtcc cagcatgtgc acagaacggt acctgccaga gggcccatgt aaagagaagc ccagggtacc ccagagcagg tagtcagagc agcccagccc gcaaagacct cccccaacat ccctgaccat acctgaacac cacttgttcc atgctgcccc caagcccaag tcaagcatgc caacacc ttc agcc tgcaag gggtgagctc accttacata tgtgcacttg ctgctgctgc gacatgacat aactcagcca ctgcacgagc aatagctgta acctcaggga gtggcctgtg gataaagttg tgcttctggg catctcagtg tgagcatcat ccttctccag aaaactgcca agtacccaaa accctccaca tctaa gctgtgggtg gtttaaaact caataagtac tgtggccatc ccagagccac ctgcaggtac acagggtgac <210> <211> 1509 <212> DNA <213> Homo sapiens <400> atgcgccagc cccagtgcgc tgggagccca ccccacctct gtcagtgctc tcctgcgggc ccgtgctggg gctgtgccct cagaagacc t ctggctgagg agcccgggtg ttgttgggct tgccttttcg accctgatcc ggtatcctag gtcagcccac gggccccagg ctcctgcagg agccccttcc ggggtggagc gccccagtgt gaggtgcgca tgggcgccag gtccagcgtc tacgcccggc cctggctga tgggagggtc tggggccctg ggcgcgccag tccagaacct agggtccggg gtggcgtctc gagactccca tccgagacc t accagtgggt ggcacgcctt cccagggggt cgggtgccct tgcagcgcgt ccgagggcgc gatcactgat cagggaccta agacattgca agcccaaccc aggctcgtgt ctcagccccc tcc aggcc cg tccagctcgt gccactgccc ttgtcagccc cctggagccc tc tccgc ccc cgctgggggt ggtccccatc cctgctcttc cgagtggacc tgtgcgcagc tgagtaccgc acagtgtgcc gcccttccat ctaccacagc ctgcgtggct cgaggaccgc gtttcgtgac cagacacatc ggggggcgat cgaggcggcc agcagccggg tggcatcgag gcaggccctg cgcagcccct agtgctgggc ctacaagaac ctgcccgatg cgacggcaca tgcggaggac ccgcgcgcgg gaccgggacc cacgagcagg ctgtgggccc ccgtgggtgt cggcgctgcc ctctgccagt ctgtacaatg ggggcgccca ttcggccgcg ggccgctgcc tgtggccgct gccggtgcct cgcgtggaac gggcgctacg ggcacgcatg cc cac ctccc t ttgagttc t ggctg'gcccc gctgtcaccc caccaccacc cgctcgccac ctggcacccc caggaccagc agccgcatac cccacggggc tgggtcgggg tcgacccccc tgctgaactg cctggacccg tccggcttcc tgccagactg g'ccgccctgt accagtgcga tcctggacgg ttagcgccgg gcggaggcgc tcgctgggta acaggagccg tgcttaatgg tggtctacac atgacctgct ggctccctcg tgaggcagcc ctgcacagac aggcccagga tgcgggcacg accgggacta tgctgctgcc gcctgactgc cgagcctctc aacccccgga gcgagagggg tggtttgggg ctgctccagc tggggaagaa ccccccaggg cc tgggcacc cctcaactgc. caccgcctgc ctgtgatggg caacgactcg ctggaacgtg caaccacctg gcac tgggtg ccgagacaca cctacaggtc ggagcgctac tcagccccgg cccaacgctg gacccgctat cgagtacgtg cctgatggct ccacgc cggc ccggcgctgt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1509 <210> 6 <211> 1356 <212> DNA <213> Homo sapiens <400> 6 atggactcgg tgggccctgc tgggtgtcct cgctgcctcc tgccagttgc Cccctctgtt ccccaggccc tgaactgtgg tttgggggtc ggacccgctg ctccagctcc ggcttcctgg ggaagaaccg cagactgccc cccaggggct cacctcttcc agtgctcagg tgcgggcgtg tgctggggag gtgcccttcc 3/79 agaacctcct gtccgggcga gcgtctctgt actcccatga gagacc taca gctcttcctg gtggaccccg gcgcagccgg gtaccgcctc gtgtgccctg tacaatggcc gcgcccaacc ggccgcgtcc cgctgcctta ggccg'ctgcg ggtgccttcg gtggaacaca cgc tacgtgc acgcatgtgg acctcccatg gagttctggc tggcccctga gtcacccctg caccaccagg tcgccactgc gcaccccacc gaccagctgc cgcatacgcc gccctgtcct agtgcgacct tggacggcac gcgccggctg gaggcgccaa cttgggtactg ggagccgcaa ttaatgggca tctacacccg acctgctcct tccctcggga ggcagcctca cacagacccc cccaggagac gggcacgcga gggactacct tgctgccCCa tgactgcccg gggcacccag caactgcctg cgcctgcagc tgatgggttg cgactcgtgc gaacgtgacc ccacctgggt ctgggtggtC agacacaggg acaggtcctc gcgctacagc gcCggggg9 aacgctggcc ccgctatgag gtacgtgtgg gatggctgtc cgccggctac gcgctgtcct aagacctacc gctgaggggc ccgggtgCCC ttgggctcgg cttttcgtgc ctgatccccg atcc taggat agcccaccag ccccaggaga ctgcaggagc cccttccagg gtggagcctc ccagtgttcc gtgcgcatc gcgccaggcc cagcgtcttg gcccggccct ggctga agtgggtgCC acgccttcta agggggtctg gtgccctcga agcgcgtgtt agggcgccag cactgatggg ggacctacga cattgcaagc ccaaccctgg ctcgtgtgca agccccccgc aggcccgagt agctcgtcta actgcccctg tcagccccga ggagccctgc cttccatggg ccacagcttc cgtggctggc ggaccgctgt tcgtgacgcc acdcatccgc gggCgatggg ggcggCCggc agccgggccc catcgagttt ggccctgggc agcccctgct gctgggccac caagaaccgc cccgatgctg cggcacacag ggaggacagc 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1356 <210> 7 <211> 1296 <212> DNA <213> Homo sapiens <400> 7 atgatccgga cgacccccgc tatctgcggc gcggagacca accacgccgg aaaaccc tgg gggtatgtag cac tcac tgg ctgacactta cacatgtaca aaccgcctgg ctggaagtgt aatttgttga. atggtgacac gcagatgatt ggaaattatg gtcctgatag cgtggaaacc cagagccccg ctcgtgcctc cgggtcccct gccaccatcc ccccattgtc gcaacatgca gtctgctgct cgccgggcgC gtgtccccag accttcgggg gtctgaacag acagcagcct ccttcacctg ccaacgtcag gcatgatgat ctcaggctcc atgttcccga tgtccatggg cgaatcgatg acgggactgg aggagttgct tgctgcgggt tggaggctga agaatggaca ggaggtcctc caacc ttcac ggcctctgcc gcccacgggC cctgctactg ccccagagcc cgccctcact tcgcgcgcag ctctcaaaag ctctgtgctg cagtacacca cggattgaca agatttgtc tgtgatcttc tgatatcctg ggtgctgcag ctcggtaccc cc gg ttc c ct gagtcgtagc cttcagacaa gtttccatat ccaggctact aaatgcctcc ccagtggctc catcgcctgc cgcgagggtt ctgctgctgc ctctccacgc accccaggcc gccctgatgc ctggcctgcc cgcagtt tct tgggcagaga agctttggtg tatgcatcgg tcccactcag cagcttctga tgcaacctgc gtcattggat caggggctgg tggagcgagg gtggaaaagg gggcaactga catctggagg ccataccttg tgctga tcctcccagg cccgcgcgct tgcggcagcc tgggctcccc tcactacgcc ggagtttccc tcattggcgt atgtgc tggg gttccaccaa agaaagtagt acaccttgat ctgccagagc agaagaacgg ttgctaacgt ctgagttcat aggatgtgtc aagagcttca tgagagagga gcacatcctg tgaccaagca ttccaggcct ctcccgcggc cagccggcgg cgtaacccgc cagcctcttc aggcaccccc actcgtggac ggagggtggt ggtgcgctac gttcagacac agaggagttg aagaagggtc tgtgtgtgac tggcatcgtg gtccactgtg cgggattggt cacataccca aggtgtcctt gagcagggcg ccactcccac gccaaccaat tgtggctgct 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1296 <210> 8 <211> 1443 -<212> DNA <213> Homo sapiens <400> 8 atgcagccct ctgctcctgc agagccctca tcgaccacac cgggacttc ccggcctcga gggtcccggc tgctgctgct ccagcctgta ccacgctggg cgcccccaga tcagtagtcc cagcacccag cgctcgtgga cggccacaac acgtttggtc acctgtgcct gcccacacca ggcctgcaag gacctgcccc 4,79 ggtggcctct acaccacgcc tgccgggcac agcaggcacg tggtcctaag gctgagtctg aggccccccc ctacgctccc ggccctgatg gcaggtttac 120 180 240 300 cagaaagggc aggcttagag caggaccggg gcctcctatt ctggcctgcc cgcagtttct tgggcagaga agctttggtg tatgcatcgg tcccactcag cagcttctga tgcaacctgc attggatctg gggctggagg agcgaggaag gaaaaggtga caactgagca ctggaggtga taccttgttc tga tacaggatgt atggcctcgt atgccctgcg ctgagctgga tcattggcgt atgtgctggg gttccaccaa agaaagtagt acaccttgat ctgccagagc agaagaacgg ttgctaacgt agttcatcgg atgtgtccac agcttcaagg gagaggagag catcctgcca ccaagcagcc caggccttgt taacc tgc gc gggcgcccag cc tcac cct g gcttgtgacc ggagggtggt ggtgcgc tac gttcagacac agaggagttg aagaagggtc tgtgtgtgac tggcatcgtg gtccactgtg gat tggtgga atacccagtc tgtccttcgt cagggcgcag ctcccacctc aaccaatcgg ggctgctgcc aatttcagct t tctggtcag gagcagattg tcggctaaag cactcactgg ctgacactta c acatgtaca aaccgcctgg ctggaagtgt aatttgttga atggtgacac gcagatcact aattatgacg ctgatagagg ggaaacctgc agccccgtgg gtgcctcaga gtcccc tgga accatcccaa acggccagac cctatgtgcc acctcatacg gtctgaacag acagcagcct ccttcacctg c caacg t cag gcatgatgat ctcaggctcc atgt tc ccga tgtccatggg ttgaccacat ggac tggccg agttgctgag tgcgggtctt aggc tgagtt atggacacca ggtcctcaaa ccttcaccca cagcctggac atgccagacc ccgcatgtgt ctctcaaaag Ctctgtgctg cagtacacca cggattgaca agatttgtcc tgtgatcttc tgatatcctg ggtgctgcag cagggcagtc gttccctcag tcgtagctgg cagacaagtg tccatatggg ggctactcat tgcctcccca gtggctctgc 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1.380 1440 1443 <210> 9 <211> 1116 <212> DNA <213> Homo sapiens <400> 9 atggatgcag ctcctcctac ccccaggctg gacactgagc ctccaggagc ggcttgactg acagctttcc tgtgactgcc cctgcctgtg ctgcctccag gtcattgcag cccactgtct gtcctagagg gtctgtgtgg caggtggaac gggccttttt ttcctcacct cggg'tcaaac tctgggggta ccacagctcc c tggagggag tgctctgtgg tcctggacct tacgcctgtc ccttccacct cttctccaga gcctcctctg ctggccccca ggcacttcac aggagggcgg cctggatgag atgggacact ttagcaatgt caccaaacgg ttctggatag cagtgaccct atcacatgac accgggtcac aaagcaagcc cggtggcagc ccacaggcaa gagtgggaac aggggcatgc cctggatgtg caaactggtc gctgctccgg tcatgtccag ctgcaaacca gcatgcggtt gcctcatggg ggagatccgc Cgctgggaat cacact ttct cagaggtgtg ctgctttggc ctttgacttt tgccaagctc tggcccccat tgccctgctg ctggaggctg cgcctcccga ctcacctcca gcagataacg accttgaggc ctccgccacc gggaagagcc gccctgatcc ttctcctgct gcttggctgg tcagtgcagc gactccctga gaccccaaca gccatggtgc ctgattgccc gtggcacctc ttctga ggccCCcgct tgtgtgactg tacctggagg aggctcagcc ttgctgccca cccttcagac tgtctggcaa tggactttgg tgaaggagtt gaaagtcggg ctggagatgg gcagggc tgg tacgggacag ggacctggct tcaccgtgcc tggcagtcgg tttggagcaa ggccctctgg ccttttcctc cacctcccag actcccactg cctggtgcgg tgccttccat actagaggaa CCCC CtaaCcc catgtccccc ttcagacatc gcctcgatgg agacccagcc gagagtaagg aggggcctat ggaagtcatc agggatccca cttcctcccc gggcaaaggt ggataaaaac 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1116 <210> <211> 1779 <212> DNA <213> Homo sapiens <400> atggatgcag ctcctcctac ccccaggctg gacactgagc tcccgcctga cctggggcct ccacagctcc ctggagggag tgctctgtgg t CCtggacct gcCtgctcca tccatggcct aaagcaagcc cggtggcagc ccacaggcaa gagtgggaac ggaattggac acaaagccta tggcccccat tgccctgctg ctggaggctg cgcctgtggg ctcagctaca ptcaccctga 5/79 ggcccccgct tgtgtgac tg tacctggagg ggctccagCa accagctctc ggctgcaggg Cettttcctc cacctcccag actcccactg gggaatgctc aacccttgag caa tcggc tc agaatcatgg ctcaaccaga ctggaggttg aagttgagca gcccgtctcc gctggggcCC ctggaggctc cgctgcaatc ctggatctgt cggctccagg catggcttga gaaacagctt acctgtgact ccccctgcct atcctgcctc tgggtcattg gcccccactg agggtcctag tatgtctgtg atccaggtgg ccagggcctt cccttcctca ggtcgggtca aactctgggg ggcctggggt ttgttctctt gggacaacca ccctcaccct cggcactagt tgcgggggCt tggaccctgg tgagctcggt cccagaatcc agctacgcct ctgccttcca tcccttctcc gccgcctcct gtgctggccc cagggcactt cagaggaggg tctcctggat aggatgggac tggttagcaa aaCcaccaaa tttttctgga cctcagtgac aacatcacat gtaaccgggt cttctcaggc cctagatgga cctggtattt ggagcgctgc ggccctaagg ggggcagctc gagcctggtt gcccttccaa catctcagcc gtcaggggca cctcctggat agacaaac tg ctggctgctc ccatcatgtc cacctgcaaa cgggcatgcg gaggcctcat actggagatc tgtcgctggg cggcacactt tagcagaggt cctctgcttt gacctttgac cactgccaag ctctctgctc tgaccctgct ggacctccgc gcttttgggg agctaggcag cctccagaag gtggctccgg gggcctttgc agggctagcc aacctcagca cagtgcctgg cctagccctt cttagagaac tggatattgg gaggctgcca aaggagctgg agatccacct ctggccatct gggctcaatc tcagcagcct ggccatcact gcactgtacc acctcagctt cctcagggtc atcccagccc gaaggctcag ccccctggtg tgcctcacct ccattgctgc ccatgccttc gtggcagata acgcccttca gacactagag gtcaccttga ggctgtctgg caacccccta cggctccgcc acctggactt tggcatgtcc caggggaaga gcctgaagga gttttcagac ccagccctga tccgaaagtc ggggcctcga gttttctcct gctctggaga tggagaccca ggggcttggc tgggcagggc tgggagagta cgctcagtgc agctacggga cagaggggcc aatgactccc tgaggacctg gctggaagtc tctgacccca acatcaccgt gccagggatc gtggccatgg tgctggcagt cggcttcctc ggcctgattg ccctttggag caagggcaaa tttgtggcac ctcggccctc tggggataaa ctcttctga 420 480 540 600 660 720 780 840 900 960 1020 1080 1140
5. 1200. 1260 1320 1380 1440 1500 1560 1620 1680 1740 1779 <210> 11 <211> 429 <212> DNA <213> Homo sapiens <400> 11 atggccaggt ccgggagctg cgagcagtca gaggctatgg ctggatgagg tacagggggc ctggctggcc ctttgctag acatgctgct aggcccgggC tcttcacctg gagatacctt ccatggggtc gacccagctg tttccagcag gctgctcctg agcgccttac cgggggctcc cccggatgca cagcgagtgg gcaaggaacc ctgctgcaag gcggtatggg ggggtcaggc cggtggagac gatgctgatg ctggccctga cctggggttc tgggggtgta tgctgaccgg tttgcggccg gatcagacat aagacagtct ccaagtcacc ttcggggcag gcaaaagtga ggagctgtgg agaattcatc cctggcccac ggcaggcgag ccaggccttt ccgagatgtc aatcagtagc 120 180 240 300r 360 420 429 <210> 12 <211> 692 <212> DNA <213> Homo sapiens <400> 12 atgtctgaag aaccgagatg catgctgctc gggatgatgt cttcagaaaa aacttgtcca gaacaaatgg aatccatgtc gaggagaaaa aagatagaca ttc tt ttggc aagtgaccta gaaataacct tgggtctggt ttttgcagat ccatccaaca tggaggagga ccatcaaact ctaagatgtg cctgggctaa gtttggaaga tgggattatc cgcgacactc aagaaaaaga aactctttgc atctaatgac gcagcaggat atttctcaag gtgccaagag gcaatggtac cagtagaaag aaaggatttt atgggactcc acatttcagg gggcatccag ctgatgttgc attaactcag aacttatcc tcacagatct ctaatcattc caaaatagtt gactgcatag cttatgtcac tctggcagaa attctgctgg ctccatctcc tgattgggct attcagagaa agcaactggg ccagtctact atacttcaga gctactattt acaagaactc agccattact gttggttctg agcaaggaat cat ttggcgt ggtgacgttg attgagtcaa caactccaac gaagaggcag ccacagatgt tacaacaaat caccctagtg catgttttcg ggaagatggC 120 180 240 300 360 420 480 540 600 660 692 tctgttccct ctccatcctt gtacgtctct aa 6/79 <210> 13 <211> 585 <212> DNA <213> Homo sapiens <400> 13 atgtggctgt atcactggtc tatggctcag tgtaacatcc atcagggaca gatgctgaca caagtgacca agcctggctt ctcaagagca ctggggaccg ccccagctct caacaacagt gc tgggagac ttgttaaaac a tcagaaaaa gttattggtg ttaacccagg tcacagctgc cccacttcct tcctctgggt gctgcttctc gaatggctcg ctacttgaag aaatggatca ccacatgttc tgggactgag cacacaaact agccacccag gttcctgttc gaacagacca a tcc tccc ag gagcagggct tggcggtgtc gagcaggagg accgtgacca agacctggaa gcagtctcag aagaccagca ctcctggagc caaagaaggt gttactccat cattgactgt aaggagctga taaagaagaa tggagaatct ttgatcttgg aatggacaac gccccctcac tgcctctgct. cttga tgccgctaaa gcagtgtgct ttggaattac tcgagtttcc caaaagagat ggtcaaagtt cacaacagca caggtccccg cctgagcatg 120 180 240 300 360 420 480 585 <210> 14 <211> 1002 <212> DNA <213> Homo sapiens <400> 14 atgaggatct gacacctgca ggaagagatg cctggcagcc aaagttgaag ggccccaagg caggggcaga aacattgggc ggtcccaaag agaggctgga aaaagtgctt attaaatttg ttcacgtgcc aatgttcagg atgagctctg gtgtggctgc gacacaactt ggtggcttct ggcaagggca gacgagacgg cggggaagga caaaaggcat ggcttgcagg aggggaataa ctttgggccc gagaagctgg aaggagatcg tcactgtggg ataagatcct acattgctgg tgtctttggt aggaccagge aggtgacagg tcacagggtt gcttgccatt ccctggaatc agcgaagggt tgggacgagt caaaggtgat gcccatggga gggtgacgtg aactggttta acccacgggg aggagagaaa gctcacggtg gtataacgaa ggtctattac caaaaatgga ctctggcggc aggagagagg ccttctgttc gaaatctgca cctgggaacc gacaaaggcg ggagagaagg caaggctcaa gagaagggcc ggtcccactg ccgggc ccca ccccagggtg gggaaaatcg ctgagcaagt ttcaaccatt ttcacctacc gtaaaaatac attgtcctgc ttcaatggct agcagcccgt cagggaac at ccggtcacaa atgcaggaga gagaacgagg gaggatcccc tccgaggaga gtcctgaggg tgggccctat agccaggagt gtgagactct ttccttcttc atgatacagc acatcactgt tgcaCaccaa agc tgaagct tgtttgctga ga aaactcacag tggtctgcct accaggacgt agcagatgga aggaaaacat gactgggcct gccaaggggc tggaaagcct ccggggaata agtcttgcca agatatgccc agcggggaaa tttctccaga agatgcttac cggggatgag tgaggacgat 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1002 <210> <211> 678 <212> DNA <213> Homo sapiens <400> atgaggatc t gacacctgca ggaagagatg acggggcccc gagaaaggga acggtgctga. aacgaattca tattacttca aatggagtaa ggcggcattg gagaggttca ctgttcagca ggtggcttct ggcaagggca gacgagacgg agggtgagcc aaatcggtga gcaagtttcc accattatga cctaccacat aaatactgca tcctgcagct atggcttgtt gcccgtga gcttgccatt ccctggaatc agcgaagggt aggagtccgg gactctagtc ttcttcagat tacagcagcg cactgttttc caccaaagat gaagctcggg tgctgatgag gaaatctgca cc tgggaacc gacaaaggcg ggaataagag ttgccaaaaa atgccca tta gggaaattca tccagaaatg gcttacatga gatgaggtgt gacgatgaca cagggaacat ccggtcacaa atgcaggaga gc tggaaagg gtgctttcac aatttgataa cgtgccacat ttcaggtgtc gctctgagga ggctgcaggt caactttcac aaactcacag tggtctgcct agctggaccc agatcgagga tgtggggctc gatcctgtat tgctggggtc tttggtcaaa ccaggcctct gacaggagga agggttcctt 120 180 240 300 360 420 480 540 600 660 678 7n79 <210> 16 <211> 618 <212> DNA <213> Homo sapiens <400> 16 atgatgaga ,a ctgcagctgg aaagaagaat accaaagaaa gagtactgta gaacattact gtgccatgta tattgtaatt aagggctacg ac tataaatg t ttgtcatat ctctcatcac tgcagtttca ttgaagagtg aagtcaaaag accatgaaat tccttcttat agaatggaat taacagaagc tccttatcac atctcgtgga cgccctag cacacaccca agaggtggat tttggaaaaa acgtgtcctt catgggaaaa gcaatatgac taggaaatgt atttgaaata ttgttcatgg gccacctgaa ctgcccctgc acagattttg ttttttagta attgaacctg aatgtttact gagctccaaa aacaggagca ccagcgtgta caaaatgaaa cacagaagtt ttctattgcc atttcccaga cagggcccgc gaatgccact acaaacaccg aaatctgtta aaggtcttgt aatacgaatc tgcaaaaacg tcctcagtga gcagcagctg agaagataaa cagaccacct aaatcatata ttgggtggca caacagattt agaaggagtg actttatagg tattcctcat ggatggtgtc 120 180 240 300 360 420 480 540 600 618 <210> 17 <211> 288 <212> DNA <213> Homo sapiens <400> 17 atggaggtgg gttgagaggg gggttggtat tgcaagtgca aacctcatca tgctgatctt agaagcaaat gtgc tgtggt gtttcaatca ctgcaaatgc tctatgcagc tgaccctttt cctcttctcc gaagcccagg aacaaagctc ctgttggccc acattgtcct ggccgatgca cattatgact accagaccct gaggattagg attgggatcc tccttatcct aggttgcaga accccaggag aggaggaagc ccaggtggag cagaaagcag agagctga 120 240 288 <210> 18 <211> 1788 <212> DNA <213> Homo sapiens <400> 18 atggaggtgg cgcgtggctg cagcagaact gtcagtacca gaggtgcagg gcccaggatg agctacagcg cccccagggc gggcaggagc gcagtgtcct gtggtgggaa gctgcagggg ggtgcccagg cctgatggca cagacgc tgt ggggagccct gctgcatact gtagcCagC attgccatgg ggtgatgcgg cttcgtgaag gtggtgctgg tcctgc tgt gaatgggatg gcacagctgt tcgagtggtt aggataccca tgcagcgcct ccggcattta gcaaggtgga cccgaggccg tggcactggg ttgggcgatc tccggtcaga agcttcgtct caggggacgc gctgggccca ccagccagct tggaactgct ctgtaggttg tggacacaga agaaggtggc gcacctaccg cagccagtgc aggctgtggc gcaacatctc ctgggcccgg ctccatctcc cctgtatagg gttctcctat acaaggtgat tgagtgccac gctgagagtt ccaggcccca ctgcctggcg tgtgcccgag cttggccgtg gggcaaggaa aggcacctac gattgcagag ggcagtgaca gtgcaatgtg ggagatggca gggtgtgggc atccagaaca ctgcctcgcc ccgttcccgg atggctagca tgtgcggggt gaggtgctgg tgcaatgtga cccgaggccc gctgtcttca gccgtggtgc accccctcca cttccagatg acctcaCccc aggacaagca gcaccagttg gaggc tggag gggaccgatc cactgcactg aaaagggccg gtggggCC tg tcaggggcac cctgcggggc agcctgggcc taccggctac aaagcctatg cctctccctg ggaggcacag ggccccccag 8179 tccccgaggg ccggctatga cagatactgc agtcccgagt tcaagattgc ctgatacccg tcctccaggt cacgcatgac cacagaagca ggcggtcaac ctccctatgc ggtaccgcat ccgctgagtg tcctggccca gtgaacgtcg ttcccccagc acctggggcc ctggctatga ggctagaggc ttcgagggtc tacatgtgcg tgtaccgcgg gactgcggct gcccttgtac gggccctgcc actgggcatt ggtggcgggt ccgcctgcag ctacctgggc gtctgctgcc ggtgcatgag cacacacdtg tctgcaggaa tgagcgattg ggtagtaggg gattcaggat cgtggatgtg gatcggccca aggccgtcat cggccgcctg gggccgacac tgccaggcc t tgggacccgg ggaggaaggt ggagactgcc ggccgccagc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 tggtgggtgg ggcgtaggcc gtagagc tgg gaaggcgtgt caggcgggca accctatttg cttggtacca agcgaccaga aggatggtgt tggggccccg accactgtgc gtgcccgctc tgcctctgct tcacttgctg ggacggagag ggcagagctg aagccatcgg ccccagcgc agggcctgtt ggtgggtaca cttcatgaag ctcagctctg tccctgccca ggagtccggc ctggaggagg ctgagactac acagcttggg tgggtgcagc atgccgacta acagtctacc cctacatgca ggggtggccc tagtcactgg aggcttcgaa aacggtga gctggtgggt ccctgtcagc gcccgaggat cagctggtac tgccctggac tgccactgtc 1440 1500 1560 1620 1680 1740 1788 <210> 19 <211> 1842 <212> DNA <213> H-omo sapiens <400> 19 atgggcgccc ctaggaatgg gctggcacag aacttcgagt accaaggata, caggtgcagc gatgccggca agcggcaagg gggccccgag gagctggcac tcctttgggc ggaatccggt ggggagcttc caggcagggg ggcagctggg ctgtccagcc cccttggaac tactctgtag cagctggaca. atggagaagg gcgggcacct gaagcagcca ctggaggctg ctgtgcaaca gtggagcgac ggccaggatg ctggtggggC gtgtaccact ggcagtgccc tttgtgcctc accatcactt tcaggcccac gatgctgggc ctgtctccat ggttcctgta cccagttctc gcctacaagg tttatgagtg tggagctgag gccgccaggc tgggctgcct gatctgtgcc cagac ttggc gtctgggcaa acgcaggcac cccagattgc agctggcagt tgctgtgcaa gttgggagat cagagggtgt tggcatccag accgctgcct gtgcccgttc tggcatggct tctctgtgcg cagaggacgg gtgtggcaga cccgaagcca gtgcccccag gctcagggcc tgctggtggg gctgcttcat gctgctgccg ccgggaggtg ctcctgcaat taggcccgag ctatgctgtc tgatgccgtg ccacaccccc agttcttcca cccaacctca ggcgaggaca cgaggcacca cgtggaggc t ggaagggacc ctaccactgc agagaaaagg gacagtgggg tgtgtcaggg ggcacctgcg gggcagcctg aacataccgg cgccaaagcc ccggcctctc agcaggaggc gggtggcccc agagctcagc gctgggagtc tcggc tgaga cgcctgggtg tgttacagtc tacaggggtg gaagaggctt ccttcgctgc ctggtccccg gtgaccggct gccccagata ttcaagtccc gtgctcaaga tccactgata gatgtcctcc cccccacgca agcacacaga gttgggcggt ggagctccct gatcggtacc actgccgctg gccgtcctgg cctggtgaac gcac ttcccc ggggcacctg ggccctggct ctacggctag tatgttcgag cctgtacatg acagtgtacc ccaggactgc tctgtccctg cggcctggag ctacacagct cagcatgccg tacccctaca gccctagtca cgaaaacggt cgctgctgct aggggccctt atgagggccc ctgcactggg gagtggtggc ttgcccgcct cccgctacct aggtgtctgc tgacggtgca agcacacaca caactctgca atgctgagcg gcatggtagt agtggattca cccacgtgga gtcggatcgg cagcaggccg ggcccggccg atgagggccg aggctgccag ggtctgggac tgcgggagga gcggggagac ggc tggccgc cccagctggt gaggccctgt tggggcccga actacagctg tgcatgccct ctggtgccac ga gctgctaatg gtaccgcgtg tgcccagcag cattgtcagt gggtgaggtg gcaggcccag gggcagctac tgccccccca. tgaggggcag cctggcagtg ggaagtggtg attggctgca agggggtgcc ggatcctgat tgtgcagacg Ccaggggag tcatgctgca cctggtagcc acacattgcc gcctggtgat ccggcttcgt aggtgtggtg tgcctccctg cagctggtgg gggtggcgta cagcgtagag ggatgaaggc gtaccaggcg ggacacccta tgtccttggt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1842 <210> 4211> 1791 <212> DNA 4213> Homo sapiens <400> atggccgcca atcatcgtca actccaccag tcactgtgta cgggccagta ggaacacggt ccgattggag cctccctctt cgacctccac ttttgctctg gaatggctac cgccagcagc tctggccgtg gttcgtgccc ctacgggggc actcccggga aacgtggccg ttcctggcag gagggctctg gcaggcttcg atctacatct cagcggatec 91n7 cgcagctgag tgggcatatg gccgggacat gcctcttcat agtggaatgc cctcagagat gcatgtacct cgtggctgac gtcctcttgt gacgtggtgg tggactggcg cacgtacgtg cgtcacctta. gtctgtCCtg ggctcaggcg ctgctggcac cctgagtaca cggcaggagg tggcatgggt ttcagaagcg tccctgctac gtgcacatct gccctgtaca ctcatcatgg tacgggcagc acctgccacc ctgccgtgga gaccaggtca tccatcctgg atcagccgcg gcctgcgggg atgcccatcg ctgacctcca cgtccccgct atcggcgtga atctacatgc ggcgtcttct gtggtggggg ccagacacgc tttgcactca gtccagattg gcaggtgatg gccatcctcc tgtctgtctt gcctgggctg ccatcgcagg tggtgggggc tggaggcagc tgccacgtac ccgggatgac tcgtgcagcg ccagctacct cattgttccc ccgaggtcgg gtctgcgggg tcttcaacag ccggcgagcg gtgtggcctg agtcagtgac ggcgacgtgc ccacgaggct ggccagccgt gtggtgc tgt agaaccttac gccaaacacc tcatgtgtgt caccaagata gaacttctac gggcctggct tgtcatcctg ctacgcccag agacgccatg ctttggcctg a-tcactgtca caagatgctc agatgatgtg ctgctccaac gctgatgatc cagcagcacc ggagctcctg gatccccgtc cagctccctg caacgagcag ggtcctggaa cctggggagc tgtggtggct ctggtggacc ccagaaacac caacatattc tcgctggacc ctctccaccA gctgtaatct acaatcaaag gccattccct cacatgtttc accatcatgg gcccgggacc cccatgggcc ggctgcgtgg atcgcctacc gcagtgatgc ctcttcacta ctggtgggac ctgcaggact gccccaccag ggggccttct t tcc tgaacc atccactacc ggaagcctgc ctggctcagg gccttctggg ttttatgcct tgtacgcggg tcctcacgct acacggacgc cttttgacca ccaggaccat gagaccccca ccacctggta tgaaccatgc tgatcataat tgccgtccga ccaagctggt tggcggcgct tggacatctg ggctggtcat ccaacagcgg tgactgcagt ggggcctgat cagccccacc tgcacttcgc tgaccccacc atgtgccctt cccgtgtctg acttcgcctg ggctctgttt cggcatcaca cctgcagacg gatcggtggt tgccaacacc cacaggggac ctggtgcacc caaggcgggc gccgggcatg gtgcctgcgg catggaactg catgtcgtcg gaggcggctg agtggcactc gcaactcttc ctttgtcctg. agcagggctg gtgcggagag tgtcgccctc cccacagagt gggaactaaa tggcttcaat a 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 132 0 1380 1440 1500 1560 1620 1680 1740 1791 <210> 21 <211> 1182 <212> DNA <213> Homo sapiens <400> 21 atggattcct tctttcctga ggctctttgg ctgactgatc tccaggagcc gaaggctcta tctgattttg ttgatggaaa ggggatgcag gaagtcctca tgtcagagtt tggcttcctc gggcagaaca aatggagacc cggttgaatc aagaggtaca cccgcacagc ctcaagccct tttctgctgg gccaggtggc taaagaatga ttgctgagaa attttgggct acatggactt aatgggacat ggccagtttt cctttgattt aacctattaa ggtttgtcct agaagatgca ctcattggcc agagtgacc t gcgtaatgga agcatggaaa aggtcacagc agtcggcagt ggc tggtggg at gcc ttcca ggctcactct tgcgtggggc gaactatgat gcttgtgaaa accaagcccc ctggggccga, gcagtctaca gtctcatctt tgcccggccc accagtacca tgtggccttt caatgccttt cagagatgtt cctggctcac ggccatccgt catggtccga cgacacac tg ggtggcagcc ctggatcgac gcagccttgg gggcac tatg caggaaggtg ctggtatttg ttgaagcatt ccatttgtgg ccattcttcc ttgtcttatg ttccagtatt gtgaagaatt ttctgatgtt tttgacaaca ccatcaagga ctactgaaag cagagttgtg ctgcttccca acactgttta caagacttgg acaacttcat ggctccatgt tgaacaccca gcccacctcc ctcaaggagt catttggcca caaatgtgaa cccagcatcc gtctttttgt catggtgtgc ccatggtggg gtagtagcca aaaattatgg acacttacaa tgaaacaagt agtgtcatcc tgcactctca cacatcctcc agactgggg catgagcagt acctcattga tggctttgtg ggaagctgct aagaagacat ga tgatttctgt caccacattc cccttccttg ctttagtttc gcatttccca gtttgttaac tattggaggc tgccaacttt tcagtcccag gatatggaca aattgtggac cactcatggt attaccagtc tgtctctatc catagaagac gcccctgagc agcgacgcac tgtctttgtg gggtgtggtg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1182 <210> 22 <211> 1572 <212> DNA <213> Homo sapiens <400> 22 atggttgggc agcgggtgct gcttctagtg gccttccttc. tttctggggt cctgctctca gaggctgcca aaatcctgac aatatctaca ctgggtggaa gccattacct actgttggac 10/79 120 cgggtgtctc agattcttca agagcatggt aagtttttga tcacc tgaag ttggatggca tgtagttatt ctggtatttg ccatttgtgg ttgtcttatg gtgaagaatt tttgacaaca ctac tgaaag ctgcttccca caagacttgg ggctccatgt gcccacctcc catttggcca cccagcatcc catggtgtgc gtagtagcca ac act tac aa agtgtcatcc cacatcctcc catgagcagt tggctttgtg aagaagacat tcccagatat atcatcaaaa gaaaagaatc tgctaagcag ttgaagcatt ccattcttcc ttccagtatt ttctgatgtt ccatcaagga cagagt tgtg acadtgttta acaac ttcat tgaacaccca ctcaaggagt caaatgtgaa gtctttttgt ccatggtggg aaaattatgg tgaaacaagt tgcactctca agactggggg acctcattga ggaagctgct ga taaagaggag aagaattaag tgaagccctt aaaggatata tgatttctgt caccacattc cccttccttg ctttagtttc gcatttccca gtttgttaac tattggaggc tgccaacttt tcagtcccag gatatggaca aattgtggac cactcatggt attaccagtc tgtctctatc catagaagac gcccctgagc agcgacgcac tgtctttgtg gggtgtggtg cataatgtga gaaaaatcat aagcattttg gtaaagctaa atggattcct tctttcctga ggctctttgg ctgactgatc tccaggagcc gaaggctcta tctgattttg ttgatggaaa ggggatgcag gaagtcctca tgtcagagtt tggcttcctc gggcagaaca aatggagacc cggttgaatc aagaggtaca cccgcacagc ctcaagccct tttctgctgg gccaggtggc ctatgct-tca accaagttat atagctacat tggaaatatt taaagaatga ttgctgagaa attttgggct acatggactt aatgggacat ggccagtttt cctttgattt aacctattaa ggtttgtcct agaagatgca ctcattggcc agagtgacct gcgtaatgga agcatggaaa aggtcacagc agtcggcagt ggctggtggg atgccttcca ggctcactct tgcgtggggc tcagagtgga caggtggttt agaaacagca tgggactcaa gaactatgat gcttgtgaaa accaagcccc ctggggccga gcagtctaca gtctcatctt tgcccggccc accagtacca tgtggccttt caatgccttt cagagatgtt cctggctcac ggccatccgt catggtccga cgacacactg ggtggcagcc ctggatcgac gcagccttgg gggcactatg caggaaggtg 180 240 300 360 420 480 540 600 660 720 780 840 900 960 10b20 1080 1140 1200 1260 1320 1380 1440 1500 1.560 1572 <210> 23 <211> 759 <212> DNA <213> Homo sapiens <400> 23 atgagctgcg caaggctacc aacgagtctc atgctgcaca acctgggatg cacgggccca tatcgctctc ccctacccga cactacacac cggaagatga tctccaaagg tgcccaccca actcccaaca tcctgggtgg t cc tgcc caa actcccgggt acaagcttcg acgaactgga ccagtctgct cggggttcca gcgagtgcaa agatagtttg ctgtctgggg ggaactggat gctatggagg cttttgcaat tgtcatcccc cgtcactctc ccgcagagcc gggccaggtg gaagtctgct ggtgtccatc tgtgcagtcc cccctggtgt ggccaccacc agaagtttgg tggagaagcc cagctgcagg gaatttgccc ttggggctgc ttagaggagc atccccaggg cagcctcagg gcagcgtggg gggcagaacc tggtatgacg c cagagaggt aacaagatcg gagaacgcgg ccctacaaga aacaacttgt tcagtc tga tgttcc tggt tgctcagcaa aggacaagga cctccaacat ccagtcagtg tgggcgctca aggtgaagga gc tcggggcc gt tgtgctgt tctactttgt atggccggcc gttaccgagg ctgcggatcc ataccagcac ggagatcctc ggagtacatg catctgggag ctggggcagg ctacacctac catgtgcacg gaacacctgc ctg'caattat ctgctctgag taggaaattt 120 180 240 300 360 420 480 540 600 660 720 759 <210> 24 <211> 1494 <212> DNA <213> Homo sapiens <400> 24 atgagctgcg caaggctacc aacgagtctc atgctgcaca acctgggatg cacgggcccat tatcgctctc tcctgggtgg tcctgcccaa actcccgggt acaagcttcg acgaactgga ccagtctgct cggggttcca tgtcatcccc cgtcactctc ccgcagagcc gggccaggtg gaagtctgCt ggtgtccatc tgtgcagtC ttggggctgc ttagaggagc atccccaggg cagcctcagg gcagcgtggg gggcagaacc tggtatgacg 11/79 tgttcctggt tgctcagcaa aggacaagga cctccaacat ccagtcagtg tgggcgc tca aggtgaagga ctgcggatcc ataccagcac ggagatcctc ggagtacatg catctgggag ctggggcagg ctacacctac ccctacccga cactacacac cggaagatga t ctcc aaagg tgcccaccca actccaaaac aaccatgttt gtcaactaca tccacgtgta ggaactctgt ctggatgaca aagtctgaga gtgtcaaaag t ttgaaaagc ccttcctact aagacagccg cccgtggata ctggggactc gcgagtgcaa agatagtttg ctgtctgggg ggaactggat gctatggagg ctgaaacgga ggc tccaacc tgacccaagt acaggtacca tc tatgaaag agggaggcc t gacacggcgt tgaaagtgca cagcaactca gggctccggt tgcacgcggg aaaagaagac ctcgggatgg cccctggtgt ggccaccacc agaagtttgg tggagaagcc cagctgcagg cgagatgaa t gagggtgatg cgtcagatgt gtgcccagca ctcgtctagc ggtggatatc gcagtccctc ggatttggac ctgcccaaga gtttggaac agtcatcagc ctacgtgggc aaaggccttc ccagagaggt aacaagatcg gagaacgcgg ccctacaaga aacaacttgt gaggtggaaa agacccacca gaca.ccaaga ggctgcctga atatgccgcg accaggaacg agcaaataca tgctacacga atccattgtc aacatctatg aacgagagtg tcgctcagga cggatctttg gctcggggcc gttgtgctgt tctactttgt atggccggcc gttaccgaga cggctcccat agcccaagaa tgaaggacag accacaaggc ccgccatcca ggaaggtccc aaccttccag ccgttgctca cggcacactg cagatacctc ggggtgacgt atggagttca ctgtcaggca catgtgcacg gaac acc tgc ctgcaattat ctgctctgag agaaacctac tcctgaagaa aacctctgcg gtgcaaaggg gaagatcttt ctacgggatc c ttcttcgtg ctcattcatg gctgtgcccg caaagacgaa aagcatctgC ggacgtgatg gtctgaaagc gtga 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1494 <21.0> <211> 1315 <212> DNA <213> Homo sapiens <400> 25 batgc tgcac gacctgggat gcacgggccc gtatcgctct cccctacccg gcactacaca ccggaagatg ttctccaaag gtgcccaccc cactccaaaa aaaccatgtt ggtcaa.ctac gtccacgtgt tggaactctg cctggatgac gaagtctgag ggtgtcaaaa gtttgaaaag accttcctac caagacagcc aacaagcttc gacgaactgg accagtctgc ccggggttcc agcgagtgca cagatagttt actgtctggg gggaactgga agctatggag cctgaaacgg tggctccaac atgacccaag aacaggtac ttctatgaaa aagggaggcc agacacggcg gtgaaagtgc ccagcaactc tgggctccgg gtgcacgcgg ggggccaggt agaagtctgc tggtgtccat atgtgcagtc acccctggtg gggccaccac gagaagtt tg ttggagaagc gcagctgcag acgagatgaa cgagggtgat tcgtcagatg agtgcccagc gctcgtctag tggtggatat tgcagtccct aggatttgga actgcccaag tgtttggaac gagtcatcag cctacgtggg gaaaggcctt gcagcctcag tgcagcgtgg cgggcagaac ctggtatgac tccagagagg caacaagatc ggagaacgcg cccctacaag gaacaacttg tgaggtggaa gagacccacc tgacaccaag aggctgcctg catatgccgc caccaggaac cagcaaatac ctgctacacg aatccattgt cadcatctat caacgagagt ctcgctcagg ccggatcttt gcctccaaca gccagtcagt ctgggcgctc gaggtgaagg tgctcggggc ggttgtgctg gtctactttg aatggccggc tgttaccgag acggctccca aagcccaaga atgaaggaca aaccacaagg gccgccatcc gggaaggtcc aaaccttcca accgttgctc ccggcacact gcagatacct gggggtgacg tggagtacat gcatctggga ac tggggcag actacaccta ccatgtgcac tgaacacctg tctgcaatta cctgctctga aagaaaccta ttcctgaaga aaacctctgc ggtgcaaagg cgaagatctt actacgggat ccttcttcgt gctcattcat agctgtgccc gcaaagacga caagcatctg tggacgtgat 12-0 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1315 gcccgtggat aaaaagaaga cctggggact cctcgggatg <210> 26 <211> .927 <212> DNA <213> Homo sapiens aatggagttc. agtctgaaag gctgtcaggc agtga <400> 26 atggttgggg ctgcatctct cccgccctag gcgctcaccg gatactttcg gcgtcctcgc acctcggcct gcaccctctc gcaacggggc gctggcgggg ctcgctgggc gggcctcctc gcgttacttc ctcctcgctg cgctctgctc ttcgtcttct cggctttcgc cagcgatctg gctggctttg gttgggccct ggtgttcgCC tcccgccgtc gagtcttggc ggtggggctg ctcctggcgc ccgccttgca gcttcttctc ctcctcggcg cgatcaccct ccacctcacc 12f79 120 180 240 300 ccctgtggcg agtcccctag ctaggcacag gctttagacc ggggatgcgg ccgcggctgc gtgcccgtgg tatgggctga ggcgtcggag ctcctgggcc tctgcccctg ccctgc tgct ctgccctcgg ccctggttgg ggggcc tggg gcgcccggct tggccgtatt tgggcggcga gcgcggggag gtgtggtgca ctcccctgtc gggttcgagg acccctggtc cctgagtctg gggcgggtac gggatacgga ggtctgcggg cggggctctg agagagctgg ttacgccccg ggccacaggg aggtaaggac cttctaa cttcctggag ttcacacgcc ttcgttcctt gcagcgctgg tggctggcag actggg'ctgg gggggtcccc ctggttttcg ctggtgatga ctgagctcac accccccagc gggccttctc acgtgcactt tggtggccgt accaaggctg ggctgtgggt tgctggccgc gtgtactccc tgctgatgag agatctgcct cccaccgcgt aatctttgct ggct cc ccac ggctgcgatg ggtgcccctc ggtggggctg ggctgtggcc cgggctggtg cctcgggggg acaactatcc 360 420 480 540 600 660 720 780 840 900 927 <210> 27 <211> 1344 <212> DNA <213> Homo sapiens <400> 27 atgacccccc gccttcgcga gaccttgccg ctggccgtgc cgccccgtgg gccagcgatc ctggtgttcg gcggtggggc cagcttcttc ctccacctca gccccaccgc tcaatctttg ttggctcccc gtggctgcga tgggtgcccc gtggtggggc gcggctgtgg cccgggctgg agcctcgggg ttcaccgcct gggttgccca gagacggggg tccactctgg agcccgccgg taaacgggct agcactttga agcaggcagc tgatggttgg tgctgcatct cccccgccct tggcgctcac tcgatacttt ccccctgtgg gtagtccc~t ctctaggcac acgctttaga tgggggatgc tcccgcggct tggtgcccgt cctatgggct tgggcgtcgg ggctcctggg ctttcctcct gggcgctgcc agctgcttcc acaccacttg acccccggat gtcctacggg ccgaagcgcc cagccccgtg gggcgtcctc ctacctcggc aggcaccc tc cggcaacggg cggctggcgg cgccctgctg agctgccctc agccctggtt ccggggcctg gggcgcccgg gctggccgta ggtgggcggC gagcgcgggg aggtgtggtg ccctcccctg gtctggttct ctcctgtggt cgctccccag ttga gggggctggg ctgctgcgct caggacactg ggcagcgccc gcctcgctgg ctgggcctc tcgcgttact gcctcctcgc ggcgctctgc c tacccc tgg ggcctgagtc gggggcgggt gggggatacg ctggtctgcg ttcggggctc gaagagagct agttacgccc caggccacag tcaggcttcc ttgatcctct ccagcctccc gcagtcttgc gctgggtggt cgctgggcct cgtggatcag tgagcacgcg gcttcgtctt tcgctggctt tctcccgccg tgctcctggc tcc tcctcgg tccttcctgg tgttcacacg acttcgttcc gagcagcgc t ggtggctggc tgactgggct gggggggtcc cgctggt ttt ggctggtgat taagggatga ccggcagctt ctccagccac tgtccCCagg ggcggccgca tgccttccct c gcc c tggc c ctggggggcc ctcggctttc tggttgggcc tcgagtcttg gcccgccttg cgcgatcacc agacccccca cc gggc ct tc ttacgtgcac ggtggtggcc agaccaaggc ggggctgtgg cctgctggcc cggtgtactc gatgctgatg gacaggagac catctacata gcctccccca aggccctggc- 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1344 <210> 28 <211> 1375 <212> DNA <213> Homo sapiens <400> 28 batggcgcgc gttcttccag gtttgtggcg cgcggtgcag gcccgtggtg tacttccttg gaccttcgct caccgggctg gtggctgctc ccacctagtg gggtggtccc aggacagagc tcggcgcttg gcgtttgagg cagtttggga atgac tggag acccacctat ccgaccctgg gcactgacag agccactacg gcctgtggtg agggcccaac cccccgacgg tgtttggggt agcaggcagc gcccggtagg gcatcttggc acctgagtat cctgcctgtc gcgtgggcct cctggagggg ctctcctccg tcacctctct gggctgggga gctccgctcc gcgcgtctcc cagtgccctg tgcgc tgggg tgggttgctg ctgttatttc ctcctccttc gtccctgctg cccaccctoc cctccatcat 13179 tgggtggtgg tttggggtct tggatcgcct agcacgaagt atgc tgc tog tcaggctctg tctcgccgac ac at ttgcCCc ctggtgtctg ctggctgagg ggccccttcc tgctctcagc tcttcgtgga ccataggaat tcgggcccag cc tct tttgc gctgggcttt gatccctggc cctttttcca ccctctccct accctgctgt tccgttacac 120 180 240 300 360 420 480 540 600 660 tgttgccctc accctgatca acactggcta cttcattccc tacctccacc tggtggccca tctccaggac ttctgacctc gacacgactc agctcaggct tctggcccca tggcctggga aggctacctc ccttctttca tacctccggg ggaggggctg agctccaggt ctggattggg gtggggcgtg ctgatgctct cccacagccc ctggccttct ctgttgcaga cgggatgtgt gggagtggca cctcaggacc gaaggaggac cttctcttgc acccactacc tggtctccgg ggaccacct t tggtggctct ccgtgctgcc tgatagagag caggcaacta ttctcctcac ttgtaacaga tgaac tcc ac cacgtcttgg tgctgccttc atggctggga gactggggtg ggctgtggcc tgaactaata catcgggggg cacggcttct cc tgcc ccac agcactagat agagtcaggc tctccacaga ctactctcag gatgcagtcc tcactagccc tacggcttca gggactagaa ctgctggggc tttgtggtgg ttct tctgct actaaagttc ccagaaagcc accacagtgc ttgttgctat cagggcctgt tgttccctgt catcaggggc ggatttactg ctcctctctc ctggggcctt tctcaactac ccctacccaa aaagcttgac cttaa 780 840 900 960 1020 1080 1140 1200 1260 1320 1375 <210> 29 <211> 510 <212> DNA <213> Homo sapiens <400> 29 atgaccatga cgcgggtctg atcaaaag agggaaagcc ggcttgatgc cacctttcac cccacgtgga gaagcgattg gctaagttct agacctctgg aaatgt ttgc tcgggcagag atgggggatc agcttgataa aggctactgg gtgttgctca ccaccccatc ataaaagaca ggccacttgt tgagatggat acattgcgtg tgtcctgcaa acaaacgtac gattctaaca gcacctcaaa ggacatagac aagcttctag gatgcaaaca ttgagggcca gaccctgctg gacggc tggg caccctgtcg gagagaatta ggtggtctct aatgacttcg gtgtgatgaa taaaacctta tcatcgcagc accacagggg gtgcctggga aggcaatcca cagcttttaa tcaatgatat ctgcgggatc ccagactctg catcatctcc acttaaattt tagcaaagag gaaaaaattc gtcaggaatt cattgctcga 120 180 240 300 360 420 480 510 <210> <211> 561 <212> DNA <213> Homo sapiens <400> 30 atgaagcctc aagacctctg gaaatgtttg gtcgggcaga catgggggat cagc ttgata caggctactg agtgttgctc gccaccccat tataaaagac acctacatcc gggccacttg ctgagatgga gacattgcgt ctgtcctgca aacaaacgta ggattc taac agcacctcaa cggacataga aaagcttcta acgcctgtac tgatgcaaac tttgagggcc ggaccctgct agacggctgg ccaccctgtc agagagaatt aggtggtctc caatgacttc g cacggctgct agtgtgatga ataaaacctt gtcatcgcag gaccacaggg ggtgcctggg aaggcaatcc tcagctttta gtcaatgata atggggacat actgcgggat accagactct ccatcatctc gacttaaatt atagcaaaga agaaaaaatt agtcaggaat tcattgctcg catgaccatg ccgcgggtct gatcaaaaaa cagggaaagc tggcttgatg gcacctttca ccccacgtgg tgaagcgatt agctaagttc 120 180 240 300 360 420 480 540 561 .<210> 31 <211> 2028 <212> DNA <213> H-omo sapiens <400> 31 atggagagcg cagaagggct gctgttggac gctggagggg agtggacatt tatgaactta attgctggtc gcaccagcag tggagcctgg tatggtccac acatggtgtg tcattggcct atggcttgtt aggtcaccac ccctcagcct ggacatcgcg agtgaagacc gtggccagtg ggcagggtca ttctgtgctg gatgccagaa ccacagttag gtgctagttc aaaagagaca ggtgcatcct ggtgctgcta atgttggcct tacctacgga 14fl9 atcc cc tgga tgtacttcct cagtgaaagg tgtttgccag cgggcatttc ggatcttcct agcgcttcgg tgcgtttccc ctttgtcctg ctacttcctg caatgttgga tgtatcagct acccatctac tggcatcaga 120 180 240 300 360 420 atccccatca gacatgtatg atagt tgggc atctacacgg tacagtttcg gctagcaacc ttccgagatc ccatccctct aacctgtccc ttcataatgg gcagatccag tatcccaaac atggtggcgg accatggacc ggcagggtgt gccagccagg cctgtggcgg ttctggggcc tacgtgcagc tacctctact tggttcacag gaccccgtgg cagaacggga aacacgtcta atcctgtggc gccatcatag attttctgcg tcctggctgt caggtgccat tactggccat atgccctgca ccgcggttgg ggagtgagaa cgctgacatc ggtactggtg atgccaaagg tgttccctgg agatctgcca tcgtgctgga ctctcatgtc tctggaatca ttgtgctgct gcggccagct tggtcttcat tgatctcggg ctcgatgcga tctccatgat agccaccctc tccagaagga tgccagaggc aaacccacag tctgtggaat tttccctgga tgagc tgcgc actctaccta cttcatccag cactgctgta gacgctgatc tgggatggaa cagcagctgc tgatctcccg cacggatcag aggtgctctg gatggtcagc gaagatctgc actcctgccc ctccctcacc cctccggcct gctggtcctg cttcatctat catgggatgt cctgctcctg ccagccagat cctgtccacg caaggagatg acaagcacca cagcagcagc ctgtgacatg acaggagaag agaaaacccc catctttatc tttatctaca cagtctttgc tacacggttg atgcttatag ggactgaagg gggctgcccc tggccgggg gtgattgtcc atggctgcat cgcatcctct agcaacccct acagggctcc tccatcttta cgggcatctg gtctccatcc atccagtcca ttctggaaga ggcttggtta gagcgcccgg gtcaccctca gtcagccacc ccagcagctc agcagcgtcc accccaaagc ggcaaggaag t tggtgaaga tggggctatt tcttcaccaa acctggatc t ctggtggcct gagcgctcac agaagtactt gggaagatgc tcctatttgg agcggactct acc tgaaggt tcccagatca caggctgttc gtgggctgat acagtgccag agaaggagc t tctggatccc tcagctccta ggaccaatga ggctggtcct tcctggtgaa tcactgtctc tgacctggtt ccttgtctct agttcgagat agtccaaagt agctcccggc ccctcctgga ttgcttag gatctcggta gtacctggcc ggctgctgtg cttgatgggc cttggccctg cttccatatt aatgtccatc ggctgccaag gctgcccctc agtggcctgt ggacatcgcg gatggctgtg caccatcttc catgattgtg tgtggtccag cctgcagccg aaagggtgcc ggactttatt gagcattcac caccgtgagc tactcgtcac taccctctct ggttcaagaa ggtgaaggcc cagagcagaa cgtcaacctc 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2028 <210> 32 <211> 1458 <212> DNA <213> Homo sapiens <400> 32 atggagccct aaggctgact gcgcgtactg tctctgtatc c tgggaagga tttggattca ggagtcaatg aaggagctcc atgggacagg ctggccagct agcccgcqct cggctccggg gcctgccagg agacaggtga gtgtacgcct tacgcgatca atcgagaggg gggagcatct gccatggcct gggatcctgg ggggcgctca gccttgtcc actggcctgt cacagactca cagtcaacag gttggggaga ggcat ttctg gagagccact ccctgggagg agaagtccc t gccgcaaagc caggtgtgag gaggagctgt tggtcggact gcctggtgcc acctcctcat gctccgggga gctgccgtgc caagcctcgt acgcctcctc tcgggac tgg tgggtcggcg tcactgtggc gcatctttgc ccacagagct tgtggatcat acttcctcta tccttcctga acttccccag aactctag aggcttgttt tccacagcac gcccgatcac cctctttgga cctggtgaat aggctccttt catgaacatc ggccatgagc cagggagctc cggggcgc tc tgactgtgga cttggcaggg ccggcgccca ggttctgggc cgtgttccgg gagctgcgag cgtgctgctc cctgtgcctg cttcatcctc gtttgaccag gctcatcctg tgtccctttc gaccaaaggc gcgggcccag catctagcac attcaggaat ctagtcctgc gcactgcttg aacatctttg gagatgatca cagcccatgt tcagccatct c taggtggcc cagctcgcct gacaccgagg gagc tggagg tgggagc tgt agtgccatgg aaggcaggag ctgctcacgg atcggtgggt cagagctcct agctttggca atggccaggc gtcggcctgg cttggtgtct aagaccttcc ggccccacgt ccccacgcca tcaccaa tga ttatgtggtc caggtccctt tggtgtcagc tgctgggaag acctggggga ttacggctct ctcaggcctg ccctgcctct cctgcctggc agctggagga tccagcatcg agctctgcgg tgccggaagc cggttgttag acagcctgat tcccctggac ttggccctgc ctgctgcctg gatttccctt gtgtctgtgg aagagatctc ggaggagcct ccatccccag gacatggcag cctcatcgtg ggccatcacg agcaatcctg actgctcgtg gagcgcccc t ggggatcgtg gcccctgctg gctccctgaa agcactacgg ggagcgcgct ggccctgagg gaatgactcg gaagatccag ttgtgtggta gacctgctgg actctacctg cggagtgacg catggtctgc tatcatggag ggccatctac caaggaat ta ggaggttatc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1458 15/79 <210> 33 <211> 1491. <212> DRA <213> Homo sapiens <400> 33 atgagagcgc ggcattggtg cacattcagg cacctagtcc ggagcactgc aataacatct tttgagatga a tccagccca agctcagcca ctcctaggtg ctccagctcg ggagacaccg ggggagctgg ccatgggagc ggcagtgcca cggaaggcag gagctgctca ctcatcggtg ctgcagagct ctcagctttg cagatggcca ctggtcggcc ttccttggtg ggcaagacct cagggcccca tccgaagact ggacttttca aattcaccaa tgcttatgtg ttgcaggtcc ttgtggtgtc tcatgctggg tgtacctggg tctttacggc gccctcaggc cctccctgcc aggcctgcct aggagc tgga tgttccagca tggagctctg gagtgccgga cggcggttgt ggtacagcc t ccttcccctg gcattggccc ggcctgctgc tgggatttcc tctgtgtctg tccaagagat -cgtggaggag gattcagggc gtttggctat tgagacatgg gtccctcatc cttggccatc agcagcaatc aagactgctc ggagagcgcc tctggggatc ctggcccctg tctgctccct ggcagcacta ggaggagcgc tcgggccctg cgggaatgac agcgaagatc tagttgtgtg gatgacctgc gacactctac tgccggagtg ctgcatggtc ctttatcatg tggggccatc ctccaaggaa aggatcctgc aacctctcta caggcgcgta gtgtctctgt acgctgggaa ctgtttggat gtgggagtca cc taaggagc gtgatgggac ctgctggcca gaaagcccgc cggcggctcc gctgcctgcc aggagacagg tcggtgtacg cagtacgcga gtaatcgaga tgggggagca ctggccatgg acggggatcc tgcggggcgc gaggccttgt tacactggcc ttacacagac tcctgaccat tcatcaatgc c tggagagcc atcccctggg ggaagaagtc tcagccgcaa atgcaggtgt tccgaggagc aggtggtcgg gctgcctggt gctacctcct ggggctccgg agggctgccg tgacaagcct cctacgcctc tcatcgggac gggtgggtcg tcttcactgt cctgcatctt tggccacaga tcatgtggat cccacttcct tgttccttcc tcaacttccc ctgcgctg cccgacct actgcccg aggcctct cctcctgg agcag'gct gagcatga tgtggcca actcaggg gCCCggg9 cattgact ggacttgg tgcccggc cgtggttc ctccgtgt tgggagct gcgcgtgc ggccc tgt tgccttca gctgttt catgctcz ctatgtcc tgagaccz caggcgg *cc .tg 120 at 180 .tt 240 rtg 300 cc 360 iac 420 itg 480 rag 540 rcg 600 ;gt 660 rca 720 :gc 780 :tg 840 :tc 900 :gc 960 tg 1020 :gc 1080 Ltc 1140 ~ac 1200 ~tc 1260 :ct 1320 iaa 1380 Icc 1440 1491 cctggaggtt atccagtcaa cagaactcta g <210> 34 <211> 1501 <212> DNA <213> Homo sapiens <400> 34 batgctccac ctgcgctgcc cccgaccttg actgcccgat aggcctcttt cctcctggtg agcaggctcc gagcatgaac tgtggccatg actcagggag gCCCgg9g cattgactgt ggacttggca tgcccggcgc cgtggttctg ctccgtgttc tgggagctgc gcgcgtgctg ggccc tgtgc tgccttcatc gctgtttgac gccctcctgc ggcattggtg cacattcagg cacctagtcc ggagcac tgc aataacatct tttgagatga a tcc agccca agctcagcca ctcctaggtg ctccagctcg ggagacaccg ggggagctgg ccatgggagc ggcagtgcca cggaaggcag gagctgctca ctcatcggtg ctgcagagct ctcagctttg cagatggcca gatctagaat ggacttttca aattcaccaa tgcttatgtg ttgcaggtcc ttgtggtgtc tcatgctggg tgtacctggg tctttacggc gccctcaggc cctccctgcc aggcctgcct aggagctgga tgttccagca tggagc tctg gagtgccgga cggcggttgt ggtacagcct ccttcccctg gcattggccc ggcc tgc tgc gattcagggc gtttggctat tgagacatgg gtccctcatc cttggccatc agcagcaatc aagactgctc ggagagcgc tctggggatc ctggcccctg tctgctccct ggcagcacta ggaggagcgc tcgggccctg cgggaatgac agcgaagatc tagttgtgtg gatgacctgc gacactctac tgccggagtg ctgcatggtc 16/79 aggatcctgc aacctctcta caggcgcgta gtgtctctgt acgctgggaa ctgtttggat gtgggagtca cctaaggagc. gtgatgggac ctgctggcca gaaagcccgc cggcggctcc gctgcctgcc aggagacagg tcggtgtacg cagtacgcga gtaatcgaga tgggggagca ctggccatgg acggggatcc tgcggggcgc tcctgaccat tcatcaatgc ctggagagcc atcccctggg ggaagaagtc tcagccgcaa atgcaggtgt tccgaggagc aggtggtcgg gctgcctggt, gctacctcct ggggctccgg agggctgccg tgacaagcct cctacgcctc tcatcgggac gggtgggtCg tcttcactgt cctgcatctt tggccacaga tcatgtggat 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 catgctcatc ctatgtccct tgagaccaaa caggcgggcc ctggtcggcc tgggatttcc ctttatcatg gaggccttgt cccacttcct ttccttggtg tctgtgtctg tggggccatc tacactggcc tgttccttcc ggcaagacct tccaagagat ctccaaggaa ttacacagac tcaacttccc cagggcccca cgtggaggag cctggaggtt atccagtcaa cagaactcta 1320 1380 1440 1500 1501 g <210> <211> 4077 <212> DNA <213> Homno sapiens <400> atggtagtgg attctctatg ttggtcatca cggcatggtc acagtggctg ctgagcgaca ctgttcccca gggctgacac gacatggatt gggcatctgc ctttggagga ataacagagg gaccagttca cggtttgtga ccccttcgta tacactgacc gacacagacg tcagtcgtgg cccccgggtc gaccgagctg cagccacctg agtgagacag ctcactcagg ggtctcttcc aagtccctga actctcagag ggcactctgg gttattaagg ccacctttgt gacatcttgg aaagcggatt aatactatcc gaaatctttg gtgcatataa attcagccta agagcaggga tatgtccaga tctgatggca gatgaacagc attgatacac actattaccc ttggtcgaaa gatgactccg gtggaaaaga atcaataatg atggcaacag ggacatggct tgaagcccat agggtcagtc gcgatgagga accttgtcat agctggcagc acctggtgct tcaccttagt tggcagaggg cagatgattc ttctccgcca aggagggggc gcaggctgtt catttagagt ttcgtatcca tggtggtaca tggacacaga aaaatcacct tgacccattt aagaactggg ggaatgtggc agatcctcaa agttgcacgt cacccaaaca acttggagga ctgatagctg taaa tgtccg agtcctatct ggaccaatga atggggaaat agggctctgt cttttaacct aaggagttac taggtgaaca gtgctgaaga cttcaggtta ttgccataag gtgtccataa ttaacttttc cagagatgtt ccattctcaa aattccccac gcttcacctt agacecagga cggtcctcat gactagaaat atttagattc tattacagag gaacacaatg tcggc c Ct C tgacctagaa tctgggtgct cggccaggtg tcgcatggtg gcctgtggat tgaaacagtg tctgctgctt aactcaccct attttatgag ctatagacac ccaggataac tcctgtggat ggaatcccag tgaccgagaa gccagcccca tacccaagcc cgtggctact tccaggtacc caccggcttc gaatgatgta tggccacatg cataaaacag ctccttggaa gccagtggat agatgtctta ggaaactgat cttggtcaat tgtatatacc gagtctgtca tatatgggtg gttgatagta tgtcgactcc tgt tgaaaac tgctttcaac aggggtggaa agagagacag tatgagagaa tgctgctgat tcatggtcac ggatcagatc agacagtttt tatagttatc agaaattggg agaagacaaa acgaaaacc t gctccggtgg acaggcccg gcagtgcggc tccagtggca gtctaccagc gatggaggag gaccagccac cccatcctgc tttgtgctgg ccccatgaga. cgaacagtga tctgggcccc catgaccctc cgcctccctc ctcacaccac ctacg ttaca ctgggtacct cagatcaacc cgagtggccc tttacccttt actattcagg gacactgatg agagtgtctg ggccgagttt gtcagtgaca gatgaagtgc gaaaatgggg gacttgatgt ggcattccag cacaccagtg gatatgtctc accatcctgc atggaaggtg ctgaatgatg atttctccag ttgaaagatc cctgtggagg ttcttcccca tttatggtga gctgatgttc atcatgaatc atagagagtt gtgattaaac cctgttgatg gataccaaga tctttggttt actggtgcct 17/79 tcacccggaa caggcagtgg tagaggtggt gctctgctcc atgatgacag gcaggcacca ctgttctcaa ccctttccct agtcaccctt agcaggaact cagagtggca atagtcctgg ctaatcagtc cggagctggg tgaggaagaa cagtgactca tggtcttgac atcataaaat agttccagtt acttgcatcc agaagggtca ttgcccatat gacagatcct cctatgccca gacatcatgt ccatactgag ctactgaaat tgactttcct cagagcagtt gtgagatagg aagaatggag ctgttgatag ataaaagtgt acatcttgtg caccaggctc tcaggcaggg accgatttgt ttgtaatcat tggaaggcat ccc tggatga agctgataaa ccagcattat taacagatgg atgagacgcc ttatcaacaa atattattcg ttgaadatat taccggtctt tccgcaaaac ggctgggct~C caagagcttt agacggctcg ggtacagttt tgccaacacg gagtgcaact cttaactacg tctcagaggc gcagcaggac gccagtcaca cgggctacag cagtggctgt gtggctgcgc gtcccccaca tgacaacccc t gc ttacaga ccaggtggaa cgtggacaac ccacatcctg ctctttcact gcatgtaggg taatggggac ggtgcccatc ccatcctact cactgccaat cttggaagat tactcaaagg cctattgcct aattggtggc ccaggcccca, tataacatca cactatagtt tgagaaatca ccacataaac atttcgttgt tcccaccaat gagtctggta. tttaactttc tggcacggt t ttatgagcat gaagcactct cagaatgac t caaaatatta ttatgggcca cacactgggc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 atgaatttta gagggcattc cgttactttt ggagtgtcc t gacttgaaca cacctggaat gctggaaaca gagtttcaag gatgtggaca aacaagc tga ctgaaattca cctgtcatgg ggcactgagt ttctatgttt gtcttggctg cgcactctag gacagagaca tatcttctca gatgacatga tat tttgcag gacgcttttc cccaggatga gggacctaat atgtgtccat tgaaagaagg gtcctgatga gcacggatca aaatctacta tcaccgatgg ataaaaagcc ttactccttt ctatcaccca tttttaccaa caagtgaaga ttcctgatac ttgacaacag ccactggcca gcttacacat acctggacaa aaatatgc ta t tgaaga tgg ttggt tgctc agtagacaga taaatttgat cgggagcatt tggcaaagtc aaacttggtt gcctggtgtg c atcc acac a acgtaaccct agtggtcacc tgagctcact ggtgcctatt gcaagacttg tagcttctcc ggtgtttgaa tgtcccccaa cttggggttc ttctcttaga aggcaaccac tgtctztaaga tggtaagta t tctgatgaca aacttaattc gtgactgatg gacattgtct actcttacaa tttaccatca tccatcacgt gctgatgatg gtctttcgga atccacaagc gtcgaagaca catggccatc aatgaaaact ttcacagtga acaaggagac atcgcagtga atgatcacaa tttatcgtga agcatcactc gaaggggcta tcccctctcc ttattacaag agtatgtcca gaataaatcc tccctgatgt cagacctact ccagggctcc ctttcactca aagtgaaaat cattccgtat tggttgtcag gagatactcc tcctattcaa taatcagcta ctgatggcac cccaagtgat ataagggggc gcaaaatatt cagaggcccc agttcacaca atgccacaag tggtagtgac aagtcttcat tttggggcaa cctcatagat gataagtaag aagc ac tagt catgcgaggt gctgcaactg ggacagtttt ctccattagc tgaaagtgaa tgacaagctc caataccaga caaacatgat ccatacagac gaagatccag ctctacactt gaaagtggag tcaacatgga agc tgacat t tgatatgttc cgcaaggaga caagtaa 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 37B0 3840 3900 3960 4020 4077 <210> 36 <211> 9318 <212> DNA <213> Homo sapiens <400> 36 atggcacgat ttgctgtccc gcgaaccgcg ctggtgttgc ctggcccagc gaggtgcgct ctgcgctatg gtcttcaccc gggaccagca gagtgccgcg cactacccgc gactgcaaag ccaaacaggg agccctgctt aacactgcac ctgacggccc ttgatcttca gatcgcagcc taccagcccc gtggatctag aacacaatgg cggcccctca gacctagaag ctgggtgctt ggccaggtgg cgcatggtgg cctgtggatg gaaacagtgc ctgctgcttt actcaccctc ttttatgagc cttggctcac ctggtctcgc gactccgggt aggtgcagcc gaccgggccg actctcacct acgcgcccgg agctggaggt atgccctgga tgggcatcct aggtccctgg ctttccagga actggatacc tgaaacgcga ccaagcccag tgaccccaga accttacttc tgcccctttc cttctgaaga aaggagcagc ctccggtggt caggccctgc cagtgcggct ccagtggcag tc tac cagca atggaggagg accagccacc ccatcctgcc ttgtgctgga cccatgagaa gaacagtgac tgcaacctcc gggggctgcaL gcctttcggc cggggaccgc cctgagtccc gggcgcgcgc aggggcagta. tgtgactcgg cgcgcggagc gtccggcttg aggagccaga ac taggcgtg catggtggtg gcacttccag tttcgtggcc catgctggca tccattccag ctccttcact ct ctgaccag ttcagaccct cacccggaat aggcagtggt agaggtggtg ctctgctcc tgatgacaga caggcaccag tgttctcaat cctttccctg gtcacccttc gcaggaactt agagtggcag acctcccggc ggggtccctg cgtgaagtct tgcgcggttt aagcgcttcc agcccgtctc gtgctaccac aacttgcctc ctggagttcg ggcgcgctgc gagggaggcg cgctatcgcc gagctgcgtt gttctggtga atgatgatga gccgaggatg cctggccagg cagagggatc gagcgcctct. tttgccttca accggtctta ccgcaaaact gctgggctcc aagagcttta gacggctcgc gtacagtttc gccaacacgg agtgcaactg ttaactacgg ctcagaggcc cagcaggaca 18/79 ccgctgcctt ctgaggaggc ggctggatcc cggtactaga cgtgcgactt gggaccgcgt tggtactgga tggtcgtgga ccttccagcc ctcgctatgg ccccggagac acacagccgc cacgaggggc ggatccgagg tggaggtgga ctgagtctcc gctacttggt tgcggctcct. t tgaactgga tggtagtggt ttctctatga tggtcatcag gqcatggtca cagtggctga tgagcgacaa tgttccccat ggctgacact acatggattc ggcatctgct tttggaggaa taacagaggg cggcagggcg catagtgctg cctgcatgac caacgacgca tggccctggc ccggctgcag ggtggaggtg agaactgctg cgagacagag agaactcctc tctcctgatg cagtcgctca tcctgtgggc aggggccgag ccagtttgta ctctgacctg gagcaccgat gaagattgcc attggaggta gaagcccatg gggtcagtct cgatgaggat ccttgtcatt gctggcagcc cctggtgctt caccttagtg ggcagagggt agatgattct tctccgccaa ggagggggca caggctgttc 120 180 240 300 360 420 480 540, 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 tatagacac t caggataacc cctgtggatc gaatcccagc gaccgagaac ccagccccac acccaagccc gtggctactc ccaggtacct accggcttca aatgatgtag ggccacatga ataaaacagg tccttggaag ccagtggatg gatgtcttag gaaactgatg ttggtcaatg gtatataccc agtctgtcag atatgggtga ttgatagtaa gtcgactccc gttgaaaaca gctttcaact ggggtggaac gagagacagt atgagagaat gctgctgatg catggtcaca gatcagatca gacagttttg atagttatcc gaaattgggg gaagaLcaaat cgaaaaccta gtagacagaa aaatttgatg gggagcattg ggcaaagtca aacttggttt cctggtgtgt atccacacag cgtaaccctg gtggtcacca gagctcactg gtgcctattc caagacttga agcttctcct gtgtttgaaa gtcccccaaa ttggggttca tctcttagat ggcaaccaca gtcttaagag ggtggaaaca aaggaatatt ggttacttgg gacaaagact ctgggcccca atgaccctcc gcctccctcc tcacaccact tacgttacac tgggtacctt agatcaacca gagtggccca ttacccttta ctattcagga. acactgatgt gagtgtctgg gccgagtttc tcagtgacag atgaagtgcc aaaatggggc acttgatgtt gcattccagc acaccagtgg ataagtctca ccatcctgcc tggaaggtga tgaatgatga tttctccagc tgaaagatct ctgtggagga tcttccccat ttatggtgat ctgatgttcc tcatgaatca tagagagttc tgattaaact ctgttgatga ataccaagat ctttggttta ctggtgcctt acttaattca tgactgatgg acattgtctt ctcttacaac ttaccatcac ccatcacgtc ctgatgatga tctttcggac tccacaagct tcgaagacag atggccatct atgaaaactt tcacagtgac caaggagacc tcgcagtgaa tgatcacaag ttatcgtgac gcatcactca aaggggctaa agttaacgta acctggtcaa gagaaacttc tcaagggcaa tagtcc tggg taatcagtcc ggagctgggc gaggaagaag agtgactcag ggtcttgact tcataaaatt gttccagttc cttgcatccc gaagggtcac tgcccatatc acagatcctg ctatgcccat acatcatgtg catactgagc tactgaaatc gactttcctc agagcagtt t tgagataggc agaatggaga tgttgatagc taaaagtgt t catcttgtgc accaggctct caggcagggc ccga tt tgta tgtaatcatt ggaaggcatg cctggatgat gctgataaat cagcattatt aacagatggg tgagac gccc tatcaacaac tattattcgt tgaaaatatc gtatgtccat aataaatccc ccctgatgtg agacctacta cagggctccc tttcactcag agtgaaaatg attccgtatc ggttgtcagt agatactcct cctattcaac aatcagctac tgatggcacc ccaagtgatg taagggggcc caaaatattg agaggcccct gttcacacaa tgccacaagt ccagaatttt tgaggactcc ttttataagt agcacagaaa ccagtcacag gggc tacagc agtggctgtc tggctgcgct ccccccacag gacaacccct gcttacagac caggtggaag gtggacaacc c aca tcc tga tctttcactc catgtagggg aatggggaca gtgcccatca catcctactg actgccaatg ttggaagatc actcaaaggg ctattgccta attggtggca caggccccag ataacatcag actatagtta gagaaatcaa c aca taaac t tttcgttgtt cccaccaatg agtctggtaa ttaactttca ggcacggttt tatgagcatg aagcac tctg agaatgacta aaaatattaa tatgggccag acactgggca ttggggcaag ctcatagatc ataagtaagg agcactagtg atgcgaggtc ctgcaactgg gacagttttg tccattagcg gaaagtgaaa gacaagctcc aataccagac aaacatgatg catacagact aagatccagg tctacacttc aaagtggagg caaca tggat gctgacattg gatatgttct cgtctgaatt aaatttctag attggcacaa caagtgcagt 19179 accagttcac ggtttgtgat cccttcgtat acactgacct acacagacga cagtcgtggt ccccgggtca accgagctgg agccacctga gtgagacaga tcactcaggc gtctcttcca agtccctgac ctctcagagt gcactctgga ttattaaggg cacctttgta acatct tgga aagcggattc atactatcca aaatctctgt tgcatataag ttcagcctac gagcagggat atgtccagag ctgatggcat atgaacagcc ttgatacacc ctattaccca tggtcgaaag atgactccga tggaaaagac tcaataatgg tggcaacaga gacatggctt tgaattttac agggcattcg gttactttta gagtgtcc tt acttgaacag acctggaatg ctggaaacaa agtttcaagt atgtggacaa acaagctgat tgaaattcac ctgtcatggt gcactgagtc tctatgtttt tcttggctgt gcactctagc acagagacag atcttctcaa atgacatgaa attttgcagt gggcatggat atgttgttct gagacagaac tcaacccagg atttagagtc tcgtatccat ggtggtacag ggacacagat aaatcacctg gacccatttt agaactgggc gaatgtggct gatcctcaac gttgcacgtg acccaaacat cttggaggac tgatagctgc aaatgtccgg gtcctatcta gaccaatgag tggggaaatc gggctctgtt ttttaacctg aggagttact aggtgaacag tgctgaagat ttcaggttat tgccataagt tgtccataaa taacttttca agagatgttt cattctcaat attccccact cttcaccttg gacccaggaa ggtcctcatt actagaaata tttagattca attacagaga ccaggatgaa ggacctaatt tgtgtccatc gaaagaaggt tcctgatgaa cacggatcag aatctactac caccgatgga taaaaagcca tactcctttt tatcacccag ttttaccaag aagtgaagat tcctgatacg tgacaacagt cactggccac cttacacatt cctggacaaa aatatgctat tgaagatggt ctcctttgaa taaacgtaga tgcagaaaaa ccagaccagg 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160' 5220 5280 5340 5400 gccacatggc gtggtactct atcgttgatc gaagatgttg atggtggtct tcttactctg gatgaacggg gaaaccttcc ggggctcaag gttgc tgaga gaggcagcca aaagacttca acatggcgag gtactctcag gttgatccag aagttacaat tcccgggaag atgataatat gacgatgtgc aactctccct gatgctgata gaacctggag cctgtgtcag gttacctttg gaaaatatga acaagagttg tatggtttct cagtacagct gaggcctgtt agatcagtgt tgcttggtaa tgcatttcag actccatgtg caagccagtg gagctcaccc gattatactg ataattggag cgcttctacc atgtcagaac ctagtgcagt cccgtggggg gtgtacgaca caaggttctc ttcaagacag a gctcagtga agtgaacca cgtgactact gaataccgcc cgattccaac ctgctctcta gatgttgctt aatctgggtg ggctatgttc tcactcttat tttggaaatc gtgaatcagc ctaggccgac gagtgcggat cagagcccgt caggagatga gtgagctgtt gttataccca attacatatc agaaactgtg atgtccttct ttacaatcgt actacagttt cccagggagg agggcaaagc tgcggatcct agcccgtgct gagatgcatg cgttcctgac atcaacatca acacatttat tctatgagga ttggggctgc agactgttat agtcggtggt tgagagtcca aagaaattga acggggtgag tagcagagat gaaaccacaa tgactgatgc tgtccatcag tatgggagtt tgaatgcaag attctacttt cattaaggat ctcagaggct ctgacccagg tcagccctga aagtgaagac agacatatcc ggaacctgaa tccttgctga cctatgtgac taggaggctg ccgccatctt tctatccaac aggctcagtt tcatgtcagc *cctataacca cagggaccta tgccagtcac aggtcagtga Lagaagagtct *ttgcagaagg actcctttta ccaagtatag atagatttaa Itcctatttac ctggatctga aatggtatat cctgagtgat gctggctgcc gccaactgtg cattcccatc acaaggaaca caggcctgag tcggatagtc gagcatgccc tcctgacaaa actgcctttc gggacgcagc acagaaacaa gagtgatggg ggctgccttg cccatggggg aaagatgatg ggaacaactt tttatgtgag ggtagaggag agttggtgaa taaatttgga tataagaatt caccaaggat gtttaaggaa agagatgaga gcagctttcc gtgctccaac taccaaaaat aggttccact cgttagctac catatttcat atactctatt gggaaaatgg tcgtggtttt catgctcccc tggcacaaga tcattatggt ttaccagtac cctagaggcc ctgtggtggc ccttcgagtc gcagcatttt gtggaatgat cagcatgcgc ccatggctta tgatcatcca gccagtacag tac tgtgaag ctgcaacCc tccagtggct ctggttgtct tgatataatt *ctgcagcatt tccaatgaat LaattgtggdC Ltgccaaacte Ltggatttaaz acatacgatc ggggagcatg ttggaattcc tttattcccc aggaggagcg gcaactggaa gaccacacca ataattgatg a tggggggaa gatgatggtc acctgttttc accagacaag gtgcagttca gagcatgagc gaattcccca gaagaatcgg gtgagtacta tctagacaga acagaaaagc ctccgcctgg caaaatgaaa gaaaccaaat ccagtgattc ggctcggcca ggggaaaccc gaggccttca aactttgagc ctcctggatt ccagaaataa accttgcgct tatgacatgt gagatggcac ttggaatgtc agaaaaataa attgaccacc gtgatctcca gttggaaacc ttcttgactg agcttgtcca tgtttatggg accattggaa cctctgtatg gacttgaagt ggaattggca atcggtgatg tttgtgctgt ggcctgacat cagtggagct *ctggtgccat *agagaacctg *gctgagttta *gatggatcca *tatggtcgtg *gagaaggtgt gcagaatatg aaagctcagc Lgcagtggatg Lgtcgactcaa :tatacagtga cattctctgg 20/79 agcagtctga aacctttcag ccacagtcgc. cactgttgag agtccaaata gagatgtgag ctgtgccgac gtgttgtccg actctttgta gaatcggatc catctgattc aaggtagcat tagctgcagt acccaggcca agtctgaaac cagtcgccac atcagagttc atttacttga aaaaatggga cctgcattct tactcggcac ctctcataag ttagtgtcac gccaaggaga cctctggaga agcacgtggt ctgttcacct tcaccctcag atactgaagt ttggagagac tctaccggaa cagaactcct c tgaaggaaa atgagagcct aaagcaaacc ccaggaaaca ctagagagct acaagtgctc atgctaccaa tcagaggttc agttcgttag cagatggaca tttcctacgt cagagcttcg gccccccaga aggggcgct t cacatcccgc tttccctccg. ttgtctctga gcactgcccc tcacctttga gcttgaacac tgggattcgg tcatggtgga ttctatgcac gctgcttagc cagagacaca accctgaagc caccactctt gatcgaaaga tgagtcaagg tccgttgaa caggagttg ttccgtgttg .t ttgacaaa :gaggaggag igagttccca caaatttaat agccacggca aaaaaagac gaccagggcc ctttcaggtg tgttgagatc ccaggggctc aaattctttt atctaaaaca tgagctgatg tccacaaagc gatccgagat tgaacccaaa cacttcaaag agactaccac tgaaatcgaa aaaacctgat ccctgatggc gaagactcat atatccttac cctgaaccta tgctgactgc gcaaagtaaa tccaaacttt atcagcacag gcccctgcag ttccaacttt caacc tcc tg aaatccagaa cactaccttg ctactatgac ggtcctaaac gttccattcc tctaactttt ggctgaactt ggccgtgcac atcctttaca cctcataagg ctttgccgta atcacatcag ccttgacatc ccaaatgtac gcaagagagt tcctgtccag tggagctgat cgactctcct agcgaccagt cattctctta tcaggtcgct caatgccaat aaagccccaa 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6000 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7 0-20 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 cgaggtattg gcaaaagaag tgtggagtac tccaccacca attggtgctg aggcaga tc c cccagctctg atctgcctca gatgccccga gacagctcag agagccgga aaaacagtcg cccatgggag cagtcagcct ctgtcattgc aaggctccag aagtttga gaagagagag aggaacaaac agcacctcca ggtcactgtg agtgctgat.q cagcagtgag atcaggagca atccagcaca gatggcatcc gtgggaggca tgcaggggca cccatggtgc caccctcact ttgccctgga tcccctggga ccacggtagg aggaaagttt ccccacagag ggcatgggag ccgcaccaag gctcaacagc gttactcac c agggggaag ccatcacaat 9000 9060 9120 9180 9240 9300 9318 <210> 37 <211> 1374 <212> DNA <213> Homo sapiens <400> 37 atggggtgta tggaggaaga tctgtcccct cggggagccc cttggggggc actcaggaca cctggggatg caccccttca ggcctcactc cctggaggtt ctgtccttcc ctggagatgc ttgggcacca aggctctttg ggtctctcca gccaagccag gtctcctacc ctcctgcagg ggccagcccc attcagactg aagaccatgg agcc tg'ggag atgagccggg gtggagcc tg tgcggacgcc tctctgcctg agggcatggc tggcttcgtg gtcctgccat gagctzagcca gagcacggat ccagtgatcc tctttggggt tgaccttcag agcacgtccg gggaggatgt acctggagga agcagc tggc gcctgacgga tgcctgtggg aggagc ttcg caagggcctc taggcttctt cgttcatggt gcggcgagga aggagtacga gggcttgagc atccatgagg ggaagtagag cgtgtggtac ggacggcatc ccgtgtgctg agggc tgggc cacctactgg aggtgagttc ctcagcagcc cctgagtgag cctggcgagg aactccaaaa gacgctgggc ccaggctgag ggctggggat cattgagcat gggcccggcg ctcgtgcctg cggctacgtg gaagaccatg taagggagat ggagtatcag tgcccttgtc aaccggagtg gtgcagatga acccggggca gggatcttct gccagcgacg tcctgtcatt gggcagaggc tgtgtggatg accggcaccc cccagcccag cagc tggaag tcagactctg agacaccgcc agacaa tgga gcagctgtcc catttcttag aaggcagcag cagcctggca cacttcaggc gtgggcggCC ggggacaagt aagcaactcg cacagacgcc gcgccgtgtg gggtgacggg ggggccatgt ttgactctcc ggcacatccc gggacttccg tgcgcatgtc tggggcccct tggcagatga aggttccccc ggctgtgggc aagctcaagg ggatcctgca agaagcagct gcatggctgc agctggacca ccaaggcccc tcttcctgtt gcccggtgcc agctgaagaa cggcagCcga tggaagagaa atcctgggcc gagcagggcc actggggcgc aggctctgtc ggcagaggat ctc tgagcag gaaccggcca cttgaacagt gcttttggtc tcatgatgtc tcagcccttc aaggctgggc agaaggggaa ggctctgcgg gggcccccag agaagcccag catcctgggc ccgcccacct ctacctcctc ccggccggcg cctcactggg agctcagggc gtga 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1374 <210> 38 <211> 1581 <212> DNA <213> Homo sapiens <400> 38 atgccggcgg cacagccctg qgcccaaggc atcctgggcc tggagcaggg ggac tggggc gtaggctctg ccggcagagg ccctctgagc cggaaccggc tccttgaaca ctgcttttgg gatcatgatg cctcagcct tcagtggtcc agacggggtg tggcattgcc tggaggaagt cctctgtccc gccggggagc tccttggggg atac tcagga agcc tgggga cacacccctt gtggcctcac tccctggagg tcctgtcctt tcctggagat aggtccctta ttctgccttc tcctcctgct cctggacccc tcctcctcta tggggctgga gcggctgacg cttctctgcc ccagggcatg gctggct tcg cagtcctgcc tggagctagc cagagcacgg tcccagtgat tttctttggg cctgaccttc gcagcacgtc cagggaggat cgcaggtttg atacccttct ccatccatga tgggaagtag gccgtgtggt tgggacggca atccgtgtgc caagggctgg atcacctact ccaggtgagt gtctcagcag agcctgagtg cgcc tggcga gtaactccaa 21n79 agtacaagct. ggagccatca ggaaccggag aggtgcagat acacccgggg tcgggatctt tggccagcga gctcctgtca gggggcagag tctgtgtgga. ccaccggcac agcccagccc ggcagctgga aatcagactc cagcttcaaa tggagacgcc tggcgccgtg gagggtgacg caggggccat ctttgactct cgggcacatc ttgggacttc gctgcgcatg tgtggggccc cctggcagat agaggttccc agggctgtgg tgaagctcaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 gcaaggctgg gcttgggcac ggagaagggg caggctctgc ctggggcccc attccatcca aaggtcggtg gatgcagctg catcatttct gcgaaggcag ctgcagcctg gtgcacttca cc tctgggtc cctgccagca aaaggctctt ggggtctctc caggccaagc ccccagggag ccctgctcca tccgcatggc tagagctgga cagccaaggc gcatcttcct ggcaggagc t ctgcaccaca tgcctgcctg tgacctggag caagcagctg caggcctgac gggtggccac tggacagtgg tgcagaagcc ccacatcctg cccccgccca gttctacctc gaacaagagc cacccccagg gagacgctgg gcccaggctg ggaggctggg ctctccatgt actctgctcc caggtctcct ggcctcctgc cctggccagc ctcattcaga cttcaggagt gccctgggga gcagacaccg agagacaatg ccctggatgc cactcaataa aggccctgca acctgcctgt aggaggagct ccccaagggc ctgtaggctt gtctgtccac ttctgaggag ccggatcctg gaagaagcag ttcctgccag ggactctgcc agagatgagg gggcattgag tcggggcccg ctcctcgtgc cttcggctac aggcagcctt gcagcctctc 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1581 <210> 39 <211> 2715 <212> DNA <213> Homo sapiens <400> 39 atgctcttgg cttgagcatt gaggtggtga gc tgaggccc gctccacttt gtaacac tga gacttccata aacggaagta ctgccccagt gtcaatagag ttccctactg aggccttgtg cagcagaagg atcacacttt aaagatgcat agccttgctg caggatattt caggtctaca agggtgaata ctccagtctg aagttatgtc gcaaagaaga gacctattgc gc tgcacaca agagtgactc catcggcact gaatctggac ctcttttctt actccaatgt cctgctctga acattggttc tggaatggaa agttcaaata agatcaaatt acccagccct go tgaaggca gggaggaaaa catgcagggg c tgaatgtca actggagggc ctctatgttc cagggaacta gtctctctgt tgacttttga ctgtgtttga atactatgta ttcatcacgc atttctctgt ggttcctgaa gtccacttct aggactggaa o tcctcgggc ggaacccaga tttgcaacat tatttgttac gtgggcaaga, tcatatatat gacggcctgc gttcgggact tggacaatct ccttcctggc gtctagttgc ctaagtccca aacctgtgat tgacttgcaa. ac tggggaga. tgtacagatg caggtgagaa ccaggaagag gactcgactc tgagatgcca acattctttc acaatggcaa tcaaaataat cagggggcca caggggatac ctcagcgttc gatactactg c tgtgagaga tgctcagtgc atctctggct ctactgcaca cactgtccct aggagccact aggagacttc caagaatggt aagtctcaaa ttcttccaac ggcacctgat gacaggcaca cttcactctt tccttgggaa cctgctcatg ggcaggt tot aggaaatgaa. agcagatcaa. cagacaaggt tggaggtgtt cttcgcctac gagcccatca catagggcca atacatcaaa atggccctgc ttccgtccat tggatttcag aaagttgacc ccaggcccgg agaagac tgt atcctcatgt cttaatcctg cagaagaagg catttctaat ttatcgatgc taaaattcaa ggctgttgaa cacattctcc cctgagagca tacagcagac gaccccaggc tcttctcctg cttatttttg gotgacaatg gtgtctcatc gtgacact tc gtggttctga aacgtcctga gacaatggtg atagtcaaaa cccactgtgg ggctcccgag attoccatta gttggaagtc ggcccttttg ttgttttatt agcagaagct aagttgtggt gagagttgtc ccagtagagc gctgatggct actcagtctc cctgcacata ggaaatcaac atccaggtgc cctccatgga ttctatgcaa ctgaccccag ggctccccac gtctctgaca agttctctaa caggcaccat aaagagaaat aaaagctggg attggatatg gggatccctg ggggagatgc tggcaccgag gagctggagc aacagctacg aacagagatg rgctgtggccc 22f79 cagctcctgt gctttggccc ctgtcctcac actcttcgct ggtgccgggc cattccttaa catatcactt tccaagtcca cct tagtga ttatgactcc ctgtggacga taacaccagg atgttcttca atatggaact atcattggtt ttccccctgg ttgtgattga at atgagtgt ggctctttac aaacacacga gcaggggcag tctccttccc ttcccaggaa ccacattctt cagagaaaac gaaacaccct gaagtaaccc agaatcctgc gtgccacttc attctgtgtt tgactgctgt atcttcttat gagacgagaa tgtctggggt tggtccttgt aggacatgca tccctgccat *gccctgtcca *gccttgtcgc tgctgtttca cagtggacag ccagcacagt cctcagctct gat cotgcaa aaaggcggaa taaaagctct tactggattt agagcatctc ga tattc toa ctggatttac tgcttgcaaa aaagagtttc cttgtccctc tggagaaaag ccagaagttc actgatgagt gatgtttcat atgggctctc tctctt-tcag aggccatgaa cttcctcaga tccagtagaa. tatago tgca caaaggagag aacatggtat cgaggttcgg tgtgcgcttg tacaaatcac tttcatagct tgaaggtgac gaaatatact cccacaagca tgatgtattt gctcctggag ctgctcogtg ggagagto tg cagacagagc *gagcatggtg cgcgggagcc c tgctggcgt 120 180 240 300 360 420 480 540 600 660 720 780- 840 900. 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 cggaggaagt cagctgggag aatgtaggag caaacaatcg gtctactctg gatgaagaaa cagtacaccc aagaagagga agagtttttc ggggtgctaa aggtaaagac gttaa caaaaaggga aggaaatcat tcacagggca tacctccagg acaacaccca gatttggtat ggcaataaaa tgcatatgga acacttctag gataactcag actctgagat atcaagaact gtactctaat aggataagga ctggaaagat ccagactac t agaacttgtt gggaac ttgc tgtctcagtt cagctctaag 2460 2520 2580 2640 2700 2715 <210> <211> 1548 <212> DNA <213> Homo sapiens <400> atgctgctgt cacaaacctg actctgactt cactactggg ggactgtaca tcttcagact c tgagatgec aacattcttt aacaatggca t tcaaaataa cagcctacag tcagacaccc agcacgtacc tgtggtzgctg gtgcagcgga gttgaagggg ttctcctggc agagcagagc gcagacaaca ccaggcaaca ctcctggctg ttgggagacg tgccctgcc ttggtatact aggacacttc ccagataac t gggcgtcctt tgatttccgt gcaatggatt gagaaaagtt gatgccaggc cc ttaatcc t acagaagaag ccatttctaa attatcgatg ttaaaattca aggggaattc cacttcactt cggaactcca aaacagtgag tccctgtgtc agatgctggt accgagagga tggagctccc gctacggccc gagatggcct tggccctgct aaaccaggct aggtggagc t ctgagatcca tagaggataa cagctggaaa gctggccttt ccatcctcca tcagttctat gaccctgacc ccggggctcc gcaggcacca gaaagagaaa taaaagctgg cattggatat agaactattt tgtaaacctg caacttcttc gctcccaacc gggtaacatc tggggtgctc ccttgtctgc catgcaggag tgccatcaga tgtccagagc tgtcgccgcg gtttcactgc ccctcccgct tcagtcgttg gactactcag ggatgtctca gatcagctct gctccagtct tggaccacat gcaacagaga ccaggaaaca ccacgaagta tattctgtgt ttgactgctg gatct tctta ggagatgaga ccacatccag agctgtgaaa agagatggcg gtctggagag cacaagcaca ctggagaccc tccgtggctg agtctgggga cagagcca tg atggtgctga ggagccactg tggcgtcgga ccaggcccag tatgttgatg ctgggagaag gttgtctact aaggatgaag gtggacaatc tcttcaaagg aaacaacatg ccctcgaggt accctgtgcg ttgaaggtga tgaaatatac tcccacaagc atgatgtatt agctgaaagc cacagcttcc aggtcatcct aaaactcagg gtccctcgct agccctcagg aaggcacagg ggaaaactca cagggggata atgtcactgt gagggctgct ggaagtcagg gagagtcctc tacaccccaa aagaggaagc ctgaggtaaa aaagttaa tgcagctgca agagagagtg gtatcatcgg tcgggaatct cttgctcttt cacattggtt ttggaatgga aagttcaaat tagatcaaat tacagactct tccagagcgg gtcagactgg atcctattgg acagatccat gggccaggct ggataccaca gcgttccctg ctactgtaca gagagagacc cagtgctctt agttggtttc ccattccatc aaagggagat taatacctcc gacacaacac 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1548 <210> 41 <211> 2494 <212> DNA <213> Homo sapiens <400> 41 batggctgtg ggtgcccacg cgaaggcaac ccgccacggc cgactgcaag gtgtacttgt cggcacgtgc gtgcgccagc cctgtgccac tccc tgc gag cgatcgctac cgagccgggc gggctgtcgc ggaggaggac tgctgcgctg tccacgtgct tacttcggtg gagc tgtgta cacgcgcggc cacccccgga gcgtgctact gcaggctggt cagcagagcg tgccagtgct taccgcggca cgccggtgtg acaaaggagt gc tggaggca cagagaacga ccaactgcga gctgccaccc gctggggcgc gcggcgcgtg gcagcgccac ggggccgcag gccgctgtca tccgcggccg agtactgtcg gccagtgcaa tagatgtcct gcaaggggac ggtgtgCgtg caccaagtgC acacgggcag gcgctgcgag ccgctgtgag gtcgcgctgc ctgcaacaac gtgccgcgag ctgccaccct cgagccgtgc gggccagcag 23/79 ccctctgctc gagtgtggga aggcctggcg ccgcgccagt tgcgaggacg catgcgtgcc tccggctggt gacccacaga cagtgcgcct cgtacgttcg gtggacggca cccgccggct ccgtgcacgg gcagc tccca ttgcggtgtg agtgccgctg tctggggccc tgacaggcca agtgccagca ggggcgcgca ccggcgcctg gcaactcgtc gcgcgcgctg cgtgtgcc tg tctacggctt tggccgaggg 120 180 240 300 360 420 480 540 600 660 720 780 ccgctgcttg cggtttctat taaccatgtc gaccaagtgt cagcggacac ccactgtaac ctgccacgag caagggcgtg gctcggc tgc ggagctttcg cagcatgaag ccaccacgac gcagccctca aggccctgtg ccccactgtc cgccgaggag ggaggggccc ggCCCggggc gccacctgac tgcagctggc caagaggaaa gacccgcgac gccctcgccg ccggcggtcc caagactcgc gccggcgccc cccagcgacc cccccggaag cgagctgggc acgtgcgagc ggcgagggct accggcaagt agcaatggca tgcgacttcc gtgacgtgcc gacacgtgcg atgggcgcgg tgctgcgctt cttgggagga ctgccccgga ctggataaca ccatcctggt tactgtgtac cctgccgagg gcgatacccc ggaggggctc gagattgggg cccgccacca cgtgcgccct cggacgccca ccaacgccgc cccagggccc cccgcgaagc agcctgggcc ccacagaaag gaaac cccgg aagaccccca agggcgggcg ccggc tggaa gcagccaccg gtacgcgctg c ttacggcga agtcggggcg cgcccggact acccggtcac gcgcgc tgct gccgcggcaa agaaggcgcc tcccgctccg cactcaactg cctctcgggc cccatgagga cgccggcgcc tccccgcgtc tgtacgcgcg gcctgtcgct agcc taaggt caccaccgcc gcgacaaatc gccccccggg gagcgcgcgc gcgccgaggc gcgccgaggt ccaagcgctc ggcctgagaa tccagaagcc cacccaccct cggaaccaag ctgtccgcca caacgcgggc ggactgcgcc ctgcctgtgc ccacggcgcg tggtgcctgc cgtcctgctc ggaccctacg gcaccgacta gaggcagaaa cagcttcctg ctccttctcc ggcaccagcg gtcccctgtg ctccgacagc cgtggcccga gtcgccatcg gtcctggatc gccaggctcc ggcgcatacg gctgcccgag cgcgccccgg tgcctccatg ggccctgggc cgtgccgcca ggcggcgacc gccgcgcaag gtag tgcgaccagc tgccgcgacg tggatcggcg ttcgtgtgcg agccctggcg gactgtgc tc cacctagaaa gtctgcctgc cgccgacccc tgcgggcgct ctacccaaag gagccaccct tcgtttgaca gagagccggg cccttgacca gagcggtcgg cgcgaggccc cccgagcgca cacggcaagc gaggccgcgc gtcgaacacg gaggcgacag cctcttggag ttggccgctg gcgcagggcc gcctcgcccg gacttgcccg aagagccggg cttgcgccac ggcatgcctg accggtgcga ccgactgcgg tccacgggcc aggcctgcag ccaaccagcg tgctctcgct gcccccgcag tcagtcgcat tcgtagtggc cagggc tgga ccactgatga accccgaagt cgccagcct6 cgtccagcgt ggccggcccg ggaaaccgcc acagcgccgc ccagccccag gcagcccccg ccctcgctgc cccacggacg acgtgcgcgg ccagggaaaa cccgcgcgcc cgcctgagac aggcggcggg 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2494 <210> 42 <211> 2614 <212> DNA <213> Homo sapiens <400> 42 batggagggc gccgtcaccg cgtggcgcct ggtgcccacg cgaaggcaac ccgccacggc cgactgcaag gtgtacttgt cggcacgtgc gtgcgccagc cctgtgccac tccctgcgag cgatcgctac cgagccgggc gggctgtcgc ccgctgcttg cggtttctat taaccatgtc gaccaagtgt cagcggacac ccactgtaac ctgccacgag caagggcgtg gcagggccc ctgctgccgt caggaactga tgctgcgctg tccacgtgct tacttcggtg gagctgtgta cacgcgcggc cacccccgga gcgtgctact gcaggctggt cagcagagcg tgccagtgct taccgcggca cgccggtgtg acgtgcgagc ggcgagggct accggcaagt agcaatggca tgcgacttcc gtgacgtgcc gacacgtgcg atgggcgcgg ggggggccgg cgctgctgct accctcgcgg gctggaggca cagagaacga ccaactgcga. gctgccaccc gctggggcgc gcggcgcgtg gcagcgccac ggggccgcag gccgc tgtca tccgcggccg agtactgtcg gccagtgcaa ccggc tggaa gcagccaccg gtacgcgctg cttacggcga agtcggggcg cgcccggact acccggtcac gcgcgctgct gccggcgcgg gctgctgctg ccgcaacgtg gcaaggggac ggtgtgcgtg caccaagtgc acacgggcag gcgctgcgag ccgctgtgag gtcgcgctgc ctgcaacaac gtgccgcgag ctgccaccct cg'agccgtgc gggccagcag cggaaccaag ctgtccgcca caacgcgggc ggactgcgcc ctgcctgtgc ccacggcgcg tggtgcctgc cgtcctgctc 24/79 cgccggggag ccggggggcc ctctggatgc tgccggacac tgccgtgctc ccggctccca gagtgtggga ttgcggtgtg aggcctggcg agtgccgctg ccgcgccagt tctggggccc tgcgaggacg tgacaggcca catgcgtgcc agtgccagca tccggctggt ggggcgcgca gacccacaga ccggcgcctg cagtgcgcct gcaactcgtc cgtacgttcg gcgcgcgctg gtggacggca cgtgtgcctg cccgccggct tctacggctt ccgtgcacgg tggccgaggg tgcgaccagc cttgcgccac tgccgcgacg ggcatgcctg tggatcggcg accggtgcga ttcgtgtgcg ccgactgcgg agccctggcg tccacgggcc gactgtgctc aggcctgcag cacctagaaa ccaaccagcg gtctgcctgc tgctctcgct 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 gctcggctgc tgctgcgctt gccgcggcaa ggaccctacg cgccgacccc gccccgcag ggagctttcg cagcatgaag ccaccacgac gcagccctca aggccctgtg ccccactgtc cgccgaggag ggaggggccc 9gCCCggggc gccacctgac tgcagctggc caagaggaaa gacccgcgac gccctcgccg ccggcggtcc caagactcgc gccggcgcc cccagcgacc cccccggaag cgagctgggc cttgggagga ctgccccgga ctggataaca ccatcc tggt tactgtgtac cctgccgagg gcgatacccc ggaggggc tc gagattgggg cccgccacca cgtgcgccct cggacgccca ccaacgccgc cccagggcCC cccgcgaagc agcctgggc ccacagaaag gaaaccccgg aagaccccca agggcgggcg agaaggcgcc tcccgctccg cactcaactg cctctcgggc cccatgagga cgccggcgCC tccccgcgtc tgtacgcgcg gcctgtcgct agcctaaggt caccaccgcc gcgacaaatc gccccccggg gagcgcgcgc gcgccgaggc gcgccgaggt ccaagcgctc ggcctgagaa tccagaagcc cacccacct gcaccgacta gaggcagaaa cagcttcctg ctccttctcc ggcaccagcg gtcccctgtg ctccgacagc cgtggcccga gtcgccatcg gtcctggatc gccaggctcc ggcgcatacg gctgccgag cgcgcccgg tgcctccatg ggccctgggc cgtgccgcca ggcggcgacc gccgcgcaag gtag tgcgggcgct ctacccaaag gagccaccct tcgtttgaca gagagccggg cccttgacca gagcggtcgg cgcgaggccc cccgagcgca cacggcaagc gaggccgcgc gtcgaacacg gaggcgacag cctcttggag ttggccgctg gcgcagggCC gcctcgcccg gacttgcccg aagagccggg tcagtcgcat tcgtagtggc cagggctgga ccactgatga accccgaagt cgccagcctc cgtccagcgt ggccggcCccg ggaaaccgcc acagcgccgc ccagccccag gcagcccccg ccctcgctgc cccacggacg acgtgcgcgg ccagggaaaa cccgcgcgcc cgcctgagac aggcggcggg 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2614 <210> 43 <211> 402 <212> DNA <213> Homo sapiens <400> 43 atcgactgcc cccgcgctgc cgagacgagc gtgcagctgc ccggtgatgt ttccgccgcc ctggccgccg gcgcggagCa gcgcgcgctt gcggccgcac tggtgcagtt gggcggcggc gggccgtacg cgtgcggctg cgcactcagc cagcggtgac ctgcggccac ccgctcatgg ctgctcgagc ctggcgtgcg cccgaggcgg ggggcggtgC tggccgtggg agggtgctgc agcgaggcca ccgactctgc tcgagttcct gctgccggac agtgaacctg cctggacgcc gggcaacagc ggtgcggtcc cgcgctgcaa taggcctgcg cctcgaccgc accaaccgtg cggggctcac cccgcggcca cgggacctgt gtgcaggccc tc <210> 44 <211> 975 <212> DNA <2 13> Homo sapiens <400> 44 atgctcaaac caggcgggca gactgccgcg gcgctgcgcg gacgagcgcg cagctgctgg gtgatgtggg cgccgcctag gccgcCgCCC ggcaagaatt atgagcctgg ctgatggCCC gtgctggagg gagggcggcc cccagcctgg ctgtctgtt cgtgc tcagc ccaaggacct aagtgcactt cggagcaggg cgcgcttcgt gccgcaccgc tgcagttcag cggcggcctg gcctgcgcct gcggccacgg cgggccggca ctctaggtgc taccaaactc gagcgccccc ccggctctgg tcggggaggc cggtgcctgg ggtaa gtgcccccga gcggggacgc gcaccttcct ggaggccatg ggcccgcttc ccgtacgccg gcggctgctg actcagcctg cggtgacccc cggccacggg cgaccgcacc gacctcggcg ccgggcgcag ggtaaccgag gccccagtct aaccttagcg ccgcctgggt gccagggccc gccgaaccct gtgttggatg ctcatggtgg ctcgagcagg gcgtgcgagC gaggcggccg gcggtgctCg aaccgtgcgg ggcggccacg ggcagcgaac gaggaggctg tcggggactg caagccccca ttgcgccgac gagagtggCC cgctggaccg ccgtggggct gtgctgcagt. gaggccacct actctgcggg agttcctggt ggctcaccgc gcggcgaggc ggcccgagct cccgcctgcg ggcggtggcg ttggcctcag gctccacagc cggagttaga cagcatcatc gccggacccc gaacctgcga ggacgccgtg caacagcccg gcggtccttc gctgcaactg tggctcagcg gggtcggagc ggctggggcC ctcacaggag tccccacccg cccagatatc ggccaacgct tgtggtgctg 120 180 240 300 360 420 480 540 600 660 720 780 840. 900 960 975 tggcaggcgg gcaccgaggc 25/79 <210> <211> 568 <212> PRT <213> homo sapiens <400> Met I 1 Asn Ala Phe Gly I Gin Pro Ile Glu Gin 145 Val Met Lys Phe Ser 225 Arg Asn Asn Gly Gin 305 Gin Ile Thr Gin Leu 385 Zys 3In ?ro det Lys ,la ksn Gln Ile 130 Val Lys Leu Glu Leu 210 Arg Ala Ala Thx Asp 290 Thr Val Gin Leu Met 370 Arg Glu 1 Cys Ala Ala Pro Val Asn I Thr 115 Gin Leu Gly Arg Asp 195 Lys Gly Asn Leu Ser 275 Glu Gin Phe Val Lys 355 Leu Gly kla lal kla lal Pro Ile His 100 Phe Met Gly Val Ser 180 Leu Ser Leu Ala Asn 260 Ala Ile Lys Lys Leu 340 Gin Asp Asp Glu B 5 Ser I Pro I Thr I Val Leu His I Lys Leu Asp Leu 165 Ser Glu Ser Glu Glu 245 Ser Glu His Ala Ser 325 Asn Gly Ser Leu let Asp Gly Giu Ala Val Arg Phe Cys Thr Asp 10 eu iys Zeu Gln 70 fly His fly Lys His 150 Lys Leu Lys Leu Asn 230 Ile Gin Ile Val Asn 310 Glu Gly Met Asn Glu 390 His Ile Val 55 Gin Asp Phe His Cys 135 Leu Asp Glu Ala Glu 215 Ala Gin Thr Gin Leu 295 Gly Met His Lys Leu 375 Asn Pro Pro 40 Phe Gln Asn Gly Met 120 Arg Gly Ala Gly Asp 200 Asn Asn Gly Gin Phe 280 Lys Arg Glu Met Asn 360 Gir Thr Gin 25 Arg Ser Thr Ile Arg 105 Glu Val Asn Thr Thx 185 Ala Thr Ser Leu Ala 265 Leu Arg Leu Asr Lys 345 Ala Lys *Ly., Glu Leu Lou Arg Thr 90 Glu Asn Asp Thr Thr 170 Asn Leu Ser Glu Lys 250 Phe Arg As; Asp Va) 330 Asr SSe3 Al. Al. Val I Val Val Pro T 75 Gly I Ala Ser Asn Asn 155 Leu Ala Thr Ile Ile 235 Glu Ile Gly Leu Gin 315 Asn iAla Ala x Ser i Leu 395 ~sp 3In rhr lal lis flu Ser ;al 140 Ala Ser Glu Phe Glu 220 Gin Asn Lys His Lys 300 Thr Thr Ser Leu Ala 380 Thr Ser 1 Ala Leu Pro Leu Met. Ala 125 Asn Asp Leu Ile Gin 205 Leu Met Leu Ser Leu 285 Met Asp Leu Arg Thr 365 Glu Met Val Thr Phe Lys Pro Arg 110 Trp Ser Ile Gin Gin 190 Thr His Leu Gin Ser 270 Glu Vai Thr Asn Glu 350 Ser Ile Glu Ala I Pro Val Pro 1 Phe Glu Val Gin Gin Thr 175 Arg Leu Vai Asn Asn 255 Phe Arg Thr Gin Ala 335 lie Gin Gin Ile let kia 7al Val flu Leu Val Leu Met 160 Gin Leu Asn Leu Ala 240 Thr Asp Ala Ala Ile 320 Gin Gin Thr Arg Gin 400 Gin Giu Gin Ser Arg Leu Lys Thr Leu His Val Val Ile Thr Ser Gin 405 410 415 2679 Glu Gin Gly Trp Lys Ser 450 Leu Ala 465 Thr Ser Gly Ser Lys Ala Trp Arg 530 Lys Trp 545 Lys Pro Leu Lys 435 Trp Ser Lys Trp Pro 515 His Asn Met Gin 420 Phe His Val Val Arg 500 Val Lys Asp Gly Arg Asn Glu Ala Tyr 485 Trp Val Asn Met Gin 565 Thr Gly Ala Ser 470 Tyr Thr Phe Gly Thr 550 Gly Gin Gly Glu 455 Lys Trp Asp Gly Gin 535 Cys Val Ser Gin 425 Ser Leu 440 Gin Phe Glu Glu Ile Gly Gly Thr 505 Phe Trp 520 Thx Glu Asp Thr Ala Leu Leu Tyr Tyr Cys Val Gin Ala 475 Leu Thr 490 Pro Phe Glu Lys Asp Cys Pro Tyr 555 Gin Phe Ser 460 Phe Asp Asn Asn Val 540 Gin Met Ser 445 Gin Leu Arg Ala Gin 525 Gin Trp Leu Val Ala Glu Thr 495 Gin Asp Gin Cys Gin Lys His Phe 480 Glu Asn Asn Gin Lys 560 <210> 46 <211> 364 <212> PRT <213> homo sapiens <400> 46 Met Ser Arg Gin Gi: 1 5 y Lys Leu Phe Ser Ala Phe Gly Val Gly Cys Cys 1n Val Thr Ala Gly Leu Pro Lys Asp Val His Asn Gly Tyr ThI Asp Ser Phe Val Leu Phe Phe 55 Ile His His Gly Phe Leu Tyr 70 Gin Val Pro Thr Gly Giu Val Val Ser Pro Ser Lys Ser Phe 100 Gly Trp Ser Pro Thr Pro Lys 115 Vai Lys Asn Gly His Ser Glu 130 135 Asp Thx Vai Gin Ile Ile Cys 145 150 Glu Lys Asn Ile Ser Cys Vai 165 Cys Ser Phe Thr Met Lys Thr 180 Gly Tyr Val Gin Pro Ser Val 195 Glu Val Asn Cys Arg Asn Glu 210 215 Thr Cys Ile Asn Gly Ile Trp Asp Asp 25 Met Asn Pro Gly Asp Glu Phe Tyr Trp Thr 105 Cys Leu 120 Ser Ser Asn Thr Glu Arg Cys Gly 185 Pro Prc 200 Tyr Ala Thr Gl. Asn Thr Pro Val Vai Glu Thx Leu Cys Glu Asp Tyr 75 Tyr Ser Cys 90 Arg Ile Thr Arg Met Cys Gly Leu Ile 140 Gly Tyr Ser 155 Gly Trp Ser 17.0 Tyr Ile Pro Tyr Gin His Met Ile Gly 220 Leu Pro Met 'er .71n ksp ksn 3iu Cys Ser 125 His Leu Thi Glu Gly 205 Asn ys rhr 7al Phe Pro Tyr Thr 110 Phe Leu Gin Pro Leu 190 Val Asn Val Ile Ala Leu Lys Pro Lys Phe Ser Asn Phe Glu Glu Pro Phe Glu Gly Asn Asn 160 Pro Ile 175 Glu Tyr Ser Val Met Ile Glu Ser 240 Thr Thr 225 230 Thr Ala Tyr Cys Giy Pro Pro Pro 235 Asn Asn Giy Asp Ser Ile 2779 Ser Cys Asn Ser 305 Asp Lys Cys Phe Gin Lys 290 Glu Gly Phe Gin Leu 260 Phe Trp Asn Leu His 340 Gly Val Lys Glu Asn 310 Ala Ala Phe Tyr Leu Pro 295 Lys Lys Met Glu Pro Gin 280 Pro Asn Thr Ile Tyr 360 250 Pro Gly 265 Gly Ser Arg Cys Asn Ile Gly Asp 330 Sex Ser 345. Pro Ile Ser Val Leu Gin 315 Ala Pro Cys Val Val 285 Pro Lys Glu Phe Thr 270 Thr Cys Trp Phe Arg 350 255 Tyr Cys Val Arg Gin 335 Ala <210> 47 <211> 327 <212> PRT <213> homo sapiens <400> 47 Met 1 Gly Leu Glu Sex Pro Ser Ile Cys Lys 145 Ser Asn Ile Pro Val 225 Lys Glu Leu Leu Leu Gly Glu Gly Tyr Asp Glu Val Phe Tyr Phe Trp Thr Lys Cys Leu Glu Ser Ser 100 Cys Asn Thr 115 Val Giu Arg 130 Thr Cys Gly Vai Pro Pro Glu Tyr Ala 180 Trp Thr Glu 195 Pro Pro Ser 210 Tyr Pro Pro Leu Gin Gly Pro Pro Arg Phe 5 Thr Glu Tyr Arg Arg Gly Gly Gly Tyr Tyr 165 Met Leu Ile Gly Ser 245 Cys Ser Leu Asp Ser Ile 70 Met Leu Tyr Trp Ile 150 Gin Ile Pro Asn Ser 230 Vai Leu Val Cys Tyr Cys 55 Thr Cys Ile Ser Ser 135 Pro His Gly Met Asn 215 Thr Thr Asp Ile Asp Asn 40 Glu Cys Ser His Leu 120 Thr Glu Gly Asn Cys 200 Gly Val Val Pro Leu Phe 25 Pro Tyr Thr Phe Leu 105 Gin Pro Leu Val Asn 185 Val Asp Thr Thr Cys 265 Ile 10 Pro Phe Asn Glu Pro 90 Glu Asn Pro Glu Ser 170 Met Glu Thr Tyr Cys 250 Val Ser Lys Ser Phe Glu 75 Phe Gly Asn Ile Tyr 155 Vai Ile Ser Thr Arg 235 Arg Val Trp Ile Gin Val Gly Vai Asp Glu Cys 140 Gly Glu Thr Thr Ser 220 Cys Asn Ser Val His Val Ser Trp Lys Thr Lys 125 Ser Tyr Val Cys Ala 205 Phe Gin Lys Glu Gly 285 Ser His Pro Pro Ser Asn Val 110 Asn Phe Val Asn Ile 190 Tyr Pro Sex Gln Glu 270 Lys Thr is Gly Thr Ser Pro Gly Gin Ile Thr Gin Cys 175 Asn Cys Leu Phe Trp 255 Asn Leu Val Phe Gly Lys Thr His Ile Ser Met Pro 160 Arg Gly Gly Ser Tyr 240 Ser Met Tyr Asn Lys Asn Asn Ile Gin Leu Lys Trp Arg Asn Asp 275 280 28/79 Ala Lys Thr Gly 290 Ala Met Ile Ser 305 Phe Giu Tyr Pro Asp Ala Vai Glu Phe Gin Cys Lys Phe Pro His Lys 295 300 Ser Pro Pro Phe Arg Ala Ile Cys Gin Giu Gly Lys 310 315 320 Ilie Cys Giu 325 <210> 48 <211> 154 <212> PRT <213> homo sapiens <400> 48 Met 1 Gly Thx Ala Lys Thr His Gly Tyr Leu 145 Ala Leu Ser Cys Asp Cys Gin Lys Ilie 130 Val Pro Trp Ser Asn Le, Gin Ser Tyr 115 Val Pro Ala Val Gin Ser Asn Thr His 100 Pro Ala Val Arg Ala 5 Ala Glu Trp Phe Ala Met Thr Phe 70 Pro Asn Gly Pro Asn Cys Cys Asp His Leu 150 Gly Vai Lys Ser 55 Leu Ile Met Arg Pro 135 Asp Cys Leu Thr 40 Ile His Ala Ser Tyr 120 Pro Lys Cys Vai 25 Gin Ile Giu Cys Leu 105 Lys Gin Val Pro Arg His Asn Pro Lys 90 Thr Giu Gin Val. Leu Ala Val Lys Phe 75 Asn Met Lys Gly Leu Lys Gin Tyr Ser Ser Gly His Asp 140 Leu Pro Pro Thr Ser Cys Glu Leu 125 Pro Leu Lys Ser Glu Vai Lys Leu 110 Asn Gly Leu Asp Pro Arg Ala Asn Thr Thr Tyr Leu Met Gin Cys Ile Cys Ser Pro Pro <210> 49 <211> 502 <212> PRT <213> homo sapiens <400> 49 Met Arg Gin Leu Gly 1 5 Ala Giu Pro Leu Pro Asp Leu Gly Arg Gly Pro Ile His Giu Gin Gin Asn Leu Leu Leu Val Ser Ala Gin Gly Arg Cys Ser Ser Ser 100 Cys Leu Arg Leu Pro 115 Tyr Arg Leu Cys Gin Gly Ser Thr Val Phe 70 Pro Cys Gly Leu Ser Ala Pro Asp 55 Leu Gly Gly Giu Pro Leu Leu Gly 40 Pro Trp Giu Arg Glu 120 Asp Arg Pro Gly Pro 25 Trp Giu Pro Arg Ala Leu Trp, Thx 90 Gly Val 105 Pro Cys Cys Pro 29n79 Pro Cys Pro GlU Leu 75 Pro Ser Trp Pro Arg Ala Ala Ala Gly Gly Arg Arg Ala Gly Pro His Asn Cys Gly Trp Val Ser Val Arg Ser 110 Gly Asp Ser 125 Gly Ala Val His Asp Arg Leu Leu Trp, Arg His Pro Gly Arg Val Phe Gly Thr Arg Giu Phe /n 130 135 140 Arg Asp Leu Gin Cys Ala Leu Tyr Asn Gly Arg Pro Val Leu Gly Thr 145 150 155 160 SGin Lys Thr Tyr Gin Trp Val Pro Phe His Gly Ala Pro Asn Gin Cys C 165 170 175 O Asp Leu Asn Cys Leu Ala Glu Gly His Ala Phe Tyr His Ser Phe Gly 180 185 190 IN Arg Val Leu Asp Gly Thr Ala Cys Ser Pro Gly Ala Gin Gly Val Cys r9l 195 200 205 Val Ala Gly Arg Cys Leu Ser Ala Gly Cys Asp Gly Leu Leu Gly Ser 210 215 220 L Gly Ala Leu Glu Asp Arg Cys Gly Arg Cys Gly Gly Ala Asn Asp Ser I 225 230 235 240 Cys Leu Phe Val Gin Arg Val Phe Arg Asp Ala Gly Ala Phe Ala Gly K 245 250 255 Tyr Trp Asn Val Thr Leu Ile Pro Glu Gly Ala Arg His Ile Arg Val /n 260 265 270 SGlu His Arg Ser Arg Asn His Leu Gly Ile Leu Gly Ser Leu Met Gly 275 280 285 Gly Asp Gly Arg Tyr Val Leu Asn Gly His Trp Val Val Ser Pro Pro 290 295 300 Gly Thr Tyr Glu Ala Ala Gly Thr His Val Val Tyr Thr Arg Asp Thr 305 310 315 320 Gly Pro Gin Glu Thr Leu Gin Ala Ala Gly Pro Thr Ser His Asp Leu 325 330 335 Leu Leu Gln Val Leu Leu Gin Glu Pro Asn Pro Gly Ile Glu Phe Glu 340 345 350 Phe Trp Leu Pro Arg Glu Arg Tyr Ser Pro Phe Gin Ala Arg Val Gin 355 360 365 Ala Leu Gly Trp Pro Leu Arg Gin Pro Gin Pro Arg Gly Val Glu Pro 370 375 380 Gin Pro Pro Ala Ala Pro Ala Val Thr Pro Ala Gin Thr Pro Thr Leu 385 390 395 400 Ala Pro Val Phe Gin Ala Arg Val Leu Gly His His His Gin Ala Gin 405 410 415 Glu Thr Arg Tyr Glu Val Arg Ile Gin Leu Val Tyr Lys Asn Arg Ser 420 425 430 Pro Leu Arg Ala Arg Glu Tyr Val Trp Ala Pro Gly His Cys Pro Cys 435 440 445 Pro Met Leu Ala Pro His Arg Asp Tyr Leu Met Ala Val Gin Arg Leu 450 455 460 Val Ser Pro Asp Gly Thr Gin Asp Gin Leu Leu Leu Pro His Ala Gly 465 470 475 480 Tyr Ala Arg Pro Trp Ser Pro Ala Glu Asp Ser Arg Ile Arg Leu Thr 485 490 495 Ala Arg Arg Cys Pro Gly 500 <210> <211> 451 <212> PRT <213> homo sapiens <400> Met Asp Ser Ala Pro Leu Phe Pro Arg Pro His Leu Phe Gin Asn Leu 1 5 10 Leu Leu Phe Leu Trp Ala Leu Leu Asn Cys Gly Leu Gly Val Ser Ala 25 30/79 l Gin Gly Pro Gly Glu Trp Thr Pro Trp Val Ser Trp Thr Arg Cys Ser 40 Ser Ser Cys Gly Arg Gly Val Ser Val Arg Ser Arg Arg Cys Leu Arg 55 Leu Pro Gly Glu Glu Pro Cys Trp Gly Asp Ser His Glu Tyr Arg Leu 0 65 70 75 Cys Gin Leu Pro Asp Cys Pro Pro Gly Ala Val Pro Phe Arg Asp Leu NO 85 90 Gin Cys Ala Leu Tyr Asn Gly Arg Pro Val Leu Gly Thr Gin Lys Thr 100 105 110 Tyr Gin Trp Val Pro Phe His Gly Ala Pro Asn Gin Cys Asp Leu Asn N 115 120 125 pg Cys Leu Ala Glu Gly His Ala Phe Tyr His Ser Phe Gly Arg Val Leu 130 135 140 C1 Asp Gly Thr Ala Cys Ser Pro Gly Ala Gin Gly Val Cys Val Ala Gly C1 145 150 155 160 LC Arg Cys Leu Ser Ala Gly Cys Asp Gly Leu Leu Gly Ser Gly Ala Leu 165 170 175 SGlu Asp Arg Cys Gly Arg Cys Gly Gly Ala Asn Asp Ser Cys Leu Phe 180 185 190 Val Gin Arg Val Phe Arg Asp Ala Gly Ala Phe Ala Gly Tyr Trp Asn 195 200 205 Val Thr Leu Ile Pro Glu Gly Ala Arg His Ile Arg Val Glu His Arg 210 215 220 Ser Arg Asn His Leu Gly Ile Leu Gly Ser Leu Met Gly Gly Asp Gly 225 230 235 240 Arg Tyr Val Leu Asn Gly His Trp Val Val Ser Pro Pro Gly Thr Tyr 245 250 255 Glu Ala Ala Gly Thr His Val Val Tyr Thr Arg Asp Thr Gly Pro Gin 260 265 270 Glu Thr Leu Gin Ala Ala Gly Pro Thr Ser His Asp Leu Leu Leu Gin 275 280 285 Val Leu Leu Gin Glu Pro Asn Pro Gly Ile Glu Phe Glu Phe Trp Leu 290 295 300 Pro Arg Glu Arg Tyr Ser Pro Phe Gin Ala Arg Val Gin Ala Leu Gly 305 310 315 320 Trp Pro Leu Arg Gin Pro Gin Pro Arg Gly Val Glu Pro Gin Pro Pro 325 330 335 Ala Ala Pro Ala Val Thr Pro Ala Gin Thr Pro Thr Leu Ala Pro Val 340 345 350 Phe Gin Ala Arg Val Leu Gly His His His Gin Ala Gin Glu Thr Arg 355 360 365 Tyr Glu Val Arg Ile Gin Leu Val Tyr Lys Asn Arg Ser Pro Leu Arg 370 375 380 Ala Arg Glu Tyr Val Trp Ala Pro Gly His Cys Pro Cys Pro Met Leu 385 390 395 400 Ala Pro His Arg Asp Tyr Leu Met Ala Val Gin Arg Leu Val Ser Pro 405 410 415 Asp Gly Thr Gin Asp Gin Leu Leu Leu Pro His Ala Gly Tyr Ala Arg 420 425 430 Pro Trp Ser Pro Ala Glu Asp Ser Arg Ile Arg Leu Thr Ala Arg Arg 435 440 445 Cys Pro Gly 450 <210> 51 <211> 431 <212> PRT 31/79 <213> homo sapiens <400> Met I I Gly Gly Leu I Pro Th~r Pro Met Gin i Ser 145 Leu Lys Gly Leu Gin. 225 Asn Gly Leu Val Gly 305 Val Gin Lys Pro Asn 385 Arg Leu :le er 'er eu ly rhr 3iy krg Lys 130 Ser rhr Phe Glu Ser 210 Ala Leu Gly Leu Pro 290 Thr Leu Gly Val Tyr 370 Gly Val Val Arg Arg Arg Leu Ala Pro Thr Ser 115 Leu Leu Leu Arg Lys 195 Tyr Pro Leu Ile Ala 275 Val Gly Ile Val Arg 355 G11 His Prc Al Thr I Gly 2 Ala I Leu I Pro 2 Gly Pro 2 100 Phe Ala Ser Thr His 180 Val Ala Val Asn Val 260 Asn Ile Arg Glu Leu 340 Glu Gin Gin Trp a Ala 420 ?ro 5 !Lrg eu eu k.rg Llal ys Pro Cys V1al Phe 165 His Val Ser Ile Val 245 Met Vai Gly Phe Glu 325 Arg Glu Lev Ala Arc 405 Alz Leu Pro Ser 2 Leu 2 Ala 70 Pro Thr Leu Leu Leu. 150 Thr Met Glu Asp Phe 230 Pro Val Ser Ser Pro 310 Leu Gly Ser Ser Thr 390 Ser Thr 3er ?ro krg krg 55 Leu Ser Leu Val Ile 135 Arg Cys Tyr Glu Thr 215 Ser Asp Thr Thr Glu 295 Gin Leu Asn Arg Thr 375 His Sex Ilc Ala Ser 2 Arg Asn 1 25 Arg Tyr 40 Gin Pro Ser Thr Ala Leu Asp Leu 105 Asp Gly 120 Gly Val Ser Phe Ser Thr Thr Asn 185 Leu Asn 200 Leu Ile His Ser Asp Ile Leu Ser 265 Val Ala 280 Phe Ile Gly Leu Ser Arg Leu Leu 345 Ala Gin 360 Ser Cys Leu Glu Asn Ala a Pro Thr 425 Ila 10 dIet Leu Jal Leu rhr 90 Arg Tyr Glu Tyr Pro 170 Val Arg Arg Ala Leu 250 Met Asp Gly Glu Ser 330 Arg Ser His Val Sex 41C His P Gin I Arg 2 Thr 2 Gly 75 Thr I Gly 2 Val Gly Val 155 Trp Ser Leu Arg Ala 235 Gin Gly Asp Ile Asp 315 Trp Val Pro Ser Thr 395 Pro Lxg ?ro -rg .rg 5er ?ro krg Gly Gly 140 Leu Ala Gly Gly Val 220 Arg Leu Val Ser Gly 300 Val Ser Phe Val His 380 Lys TyX Leu I Thr C Leu I Ala Pro Gly] Ala Leu 125 His Gly' Glu Leu Met 205 Leu Ala Leu Leu Asn 285 Gly Ser Glu Arg Glu 365 Leu Gin Leu jeu ;ly eu 7lu Ser Leu Gln 110 Asn Ser Val Ser Thr 190 Met Glu Val Lys Gin 270 Arg Asn Thr Glu Gin 350 Ala Val Prc Val Leu I Arg Leu I Thr Leu Thr Ala Ser Leu Arg Ser 175 Ser Ile Val Cys Lys 255 cys Cys Tyr Tyr Glu 335 Val Glu Pro Thr Pro 415 !ro flu jeu vhr ?he rhr Leu Ser Asp Tyr 160 Thr Phe Asp Ser Asp 240 Asn Asn Ser Asp Pro 320 Leu Glu Phe Gin Asn 400 Gly Phe Thr Gin Trp Leu Cys 430 32/79 t <210> 52 <211> 480 <212> PRT <213> homo sapiens 0 <400> 52 Met Gin Pro Ser Gly Leu Glu Gly Pro Gly Thr Phe Gly Arg Trp Pro C0 1 5 10 Leu Leu Ser Leu Leu Leu Leu Leu Leu Leu Leu Gin Pro Val Thr Cys 25 Ala Tyr Thr Thr Pro Gly Pro Pro Arg Ala Leu Thr Thr Leu Gly Ala 40 I Pro Arg Ala His Thr Met Pro Gly Thr Tyr Ala Pro Ser Thr Thr Leu 55 Ser Ser Pro Ser Thr Gin Gly Leu Gin Glu Gin Ala Arg Ala Leu Met CK 65 70 75 Arg Asp Phe Pro Leu Val Asp Gly His Asn Asp Leu Pro Leu Val Leu 0 85 90 SArg Gin Val Tyr Gin Lys Gly Leu Gin Asp Val Asn Leu Arg Asn Phe S100 105 110 Ser Tyr Gly Gin Thr Ser Leu Asp Arg Leu Arg Asp Gly Leu Val Gly 115 120 125 Ala Gin Phe Trp Ser Ala Tyr Val Pro Cys Gin Thr Gin Asp Arg Asp 130 135 140 Ala Leu Arg Leu Thr Leu Glu Gin Ile Asp Leu Ile Arg Arg Met Cys 145 150 155 160 Ala Ser Tyr Ser Glu Leu Glu Leu Val Thr Ser Ala Lys Gly Leu Asn 165 170 175 Ser Ser Gin Lys Leu Ala Cys Leu Ile Gly Val Glu Gly Gly His Ser 180 185 190 Leu Asp Ser Ser Leu Ser Val Leu Arg Ser Phe Tyr Val Leu Gly Val 195 200 205 Arg Tyr Leu Thr Leu Thr Phe Thr Cys Ser Thr Pro Trp Ala Glu Ser 210 215 220 Ser Thr Lys Phe Arg His His Met Tyr Thr Asn Val Ser Gly Leu Thr 225 230 235 240 Ser Phe Gly Glu Lys Val Val Glu Glu Leu Asn Arg Leu Gly Met Met 245 250 255 Ile Asp Leu Ser Tyr Ala Ser Asp Thr Leu Ile Arg Arg Val Leu Glu 260 265 270 Val Ser Gin Ala Pro Val Ile Phe Ser His Ser Ala Ala Arg Ala Val 275 280 285 Cys Asp Asn Leu Leu Asn Val Pro Asp Asp Ile Leu Gin Leu Leu Lys 290 295 300 Lys Asn Gly Gly Ile Val Met Val Thr Leu Ser Met Gly Val Leu Gin 305 310 315 320 Cys Asn Leu Leu Ala Asn Val Ser Thr Val Ala Asp His Phe Asp His 325 330 335 Ile Arg Ala Val Ile Gly Ser Glu Phe Ile Gly Ile Gly Gly Asn Tyr 340 345 350 Asp Gly Thr Gly Arg Phe Pro Gin Gly Leu Glu Asp Val Ser Thr Tyr 355 360 365 Pro Val Leu Ile Glu Glu Leu Leu Ser Arg Ser Trp Ser Glu Glu Glu 370 375 380 Leu Gin Gly Val Leu Arg Gly Asn Leu Leu Arg Val Phe Arg Gin Val 385 390 395 400 Glu Lys Val Arg Glu Glu Ser Arg Ala Gin Ser Pro Val Glu Ala Glu 405 410 415 Phe Pro Tyr Gly Gin Leu Ser Thr Ser Cys His Ser His Leu Val Pro 33/79 420 Gin Asn Gly His Gin 435 Asn Arg Val Pro Trp 450 Gly Leu Val Ala Ala 465 <210> 53 <211> 371 <212> PRT <213> homo sapiens 425 430 Ala Thr His Leu Glu Val Thr Lys Gin Pro Thr 440 445 Arg Ser Ser Asn Ala Ser Pro Tyr Leu Val Pro 455 460 Ala Thr Ile Pro Thr Phe Thr Gin Trp Leu Cys 470 475 480 <400> 53 Met Asp 1 Leu Leu Ala Val Arg Gin Leu Asp Leu Gin His Ala Asn Ala Leu Val 130 Leu Leu 145 Pro Ala Phe Ser Ile Arg Ala Val 210 Trp Met 225 Val Leu Arg Gly Leu Arg Leu Ser 290 Leu Asp 305 Phe Leu Ala Phe Cys Leu Leu Glu Phe Leu 115 Thr Trp Cys Asp Lys 195 Phe Arg Glu Ala Thr 275 Asp Ser Thr kla Leu Asp Glu Ser Leu His 100 Gin Leu Leu Ala Ile 180 Ser Ser Pro Asp Tyr 260 Trp Pro Arg Ser Thr 5 Leu Cys Ala Gly Arg Gly Thr Arg Leu Gly 165 Leu Gly Cys His Gly 245 Val Leu Asn Gly Val 325 Ala Leu Thr Val Asn 70 Leu Leu Leu Leu Arg 150 Pro Pro Pro Ser Gly 230 Thr Cys Glu Ile Val 310 Thr Pro Leu Ser Pro I 55 Arg Ser Thr Glu Ser 135 Leu His Pro Arg Gly 215 Ala Leu Val Vai Thr 295 Ala Leu Llys Pro 3Gl 40 Gly Leu Gly Ala Glu 120 Gly Arg His Gly Trp 200 Asp Trp Glu Val Ile 280 Val Met Cys Gin Gly 25 Pro Gly Pro Ala Phe 105 Thr Asn His Val His 185 Val Gly Leu Ile Ser 265 Gin Pro Vai Phe Ala 10 Gly Gln Leu Lys Cys 90 His Ala Pro Leu Gin 170 Phe Ile Asp Gly Arg 250 Asn Val Gly Leu Gly 330 Trp Ser Ala Pro Ala 75 Leu Leu Phe Leu Asp 155 Gly Thr Ala Pro Arg 235 Ser Val Glu Ile Ala 315 Leu Pro ly Val Leu Gin Thr Leu Pro Thr 140 Phe Lys Cys Glu Ala 220 Ala Val Ala Pro Pro 300 Val Ile Pro Gly Leu Asp Pro Ser Asp Ser 125 Cys Gly Ser Lys Glu 205 Pro Gly Gin Gly Pro 285 Gly Gly Ala Trp Ser Cys Thr Leu Ile Val 110 Pro Asp Met Leu Pro 190 Gly Thr Arg Leu Asn 270 Asn Pro Phe Leu Pro Cys ly Glu Val Ala Ala Asp Cys Ser Lys 175 Ala Gly Val Val Arg 255 Asp Gly Phe Leu Trp 335 Pro Pro His Leu Arg Ala Asp Lys Arg Pro 160 Glu Leu His Ser Arg 240 Asp Ser Thr Phe Pro 320 Ser Lys Gly Lys Gly Arg 340 Val Lys His His Met Thr Phe Asp Phe Val Ala 345 34n9 350 Pro Arg Pro Ser Gly Asp Lys Asn Ser Gly Gly Asn Arg Val Thr Ala 355 360 365 Lys Leu Phe 370 <210> 54 <211> 592 <212> PRT <213> homo sapiens <400> 54 Met 2 1 Leu Ala Arg Leu Ser Ser Leu. Ser Val 145 Leu Ala Ser Leu Arg 225 Leu Leu Tyr Ser Leu 305 His Gin Leu ksp eu al Gln Asp Arg Thr Arg Gly 130 Leu Glu Gly Thr Arg 210 Gly Glu Ala His Ala 290 Arg Gly Thr Ar Ala Phe Cys Leu Leu Leu Leu Leu 115 Leu Phe Val Leu Val 195 Leu Leu Ala Ile Leu 275 Ile Leu Leu Leu Leu 355 kla Leu I A.sp Glu. Ser Ser Glu 100 Gln 4 Ser Leu. Gly. Ala 180 Pro Arg Gly Leu Thr 260 Ser Pro Ser Thr Glu 340 Ser Chr 5 eu -ys kla Gly Leu Pro Gly Ala Asp Asp 165 Lys Gly Glu Gin Asp 245 Arg Phe Ala Gly Ala 325 Glu Gl Ala Pro I Leu Leu P Thr Ser C 4 Val Pro C 55 Asn Arg I 70 Leu Gin Gly Ala Asn Arg Leu Thr 135 Gly Ala 150 Asn His Leu Ser Leu Ala Leu Asp 215 Leu Lys 230 Pro Gly Cys Asn Leu Arg Arg Arg 295 Ala Cys 310 Phe His Thr Ala Asn Pro ~ys 7ro ln 00 ly jeu ;lu Phe Leu 120 Leu Phe Leu Thr Leu 200 Ile Glu Ser Leu Val 280 Leu Leu Let PhE Let 36C Gin 2 Gly 25 Pro Gly Trp Leu His I 105 Arg Leu Gly Val Leu 185 Ala Gly Leu Leu Ser 265 Leu Ser Thr Leu Pro 345 1 Thr kla. LO 31Y In Leu Gly Asp 90 31y Ile Asp Glu Phe 170 Thx Arg Arg Glu Val 250 Ser Asp Pro Sex Asp 330 Se. Cy Trp I Ser Ala Pro I Leu 75 Leu Leu Met Leu Leu 155 Val Leu Leu Leu Ile 235 Gly Val Leu Leu Ile 315 Val Pro Asp ?ro 3ly lal eu 3Gl Ser GIn ly Arg 140 Gly Ala Glu Pro Pro 220 His Leu Pro Sex Val 300 Ala Ale Asi CYI Pro Gly Leu Asp Gin Tyr Ser Pro 125 Leu Ser Pro Arg Ala 205 Ala Leu Asn Phe Gin 285 Arg Ala Asp Lys s Arg 365 rrp Ser Ehr Gly Asn Leu 110 Gly Asn Leu Gly Cys 190 Leu Gly Trp Leu Gln 270 Asn Leu His Asr Let Le Pro 1 Cys Gly I Glu I Met I Gin Leu. Val Gin Gin Ala 175 Asn Val Ala Pro Ser 255 Ala Pro Gin Ala i Ala 335 1 Val i Leu !ro ?ro lis .eu eu eu Thr Phe lie Lys 160 Phe Leu Ala Leu Ser 240 Ser Leu Ile Glu Phe 320 Leu Thr Trp Leu Leu Arg Leu Arg His Leu Asp Phe Cly Met Ser Pro Pro Ala Cys 35n9 370 375 380 SAla Gly Pro His His Val Gin Gly Lys Ser Leu Lys Glu Phe Ser Asp 385 390 395 400 1Ile Leu Pro Pro Gly His Phe Thr Cys Lys Pro Ala Leu Ile Arg Lys 405 410 415 O Ser Gly Pro Arg Trp Val Ile Ala Glu Glu Gly Gly His Ala Val Phe 420 425 430 \s Ser Cys Ser Gly Asp Gly Asp Pro Ala Pro Thr Val Ser Trp Met Arg C1 435 440 445 Pro His Gly Ala Trp Leu Gly Arg Ala Gly Arg Val Arg Val Leu Glu 450 455 460 V) Asp Gly Thr Leu Glu Ile Arg Ser Val Gin Leu Arg Asp Arg Gly Ala IN 465 470 475 480 Cr Tyr Val Cys Val Val Ser Asn Val Ala Gly Asn Asp Ser Leu Arg Thr 485 490 495 Trp Leu Glu Val Ile Gin Val Glu Pro Pro Asn Gly Thr Leu Ser Asp in 500 505 510 Pro Asn Ile Thr Val Pro Gly Ile Pro Gly Pro Phe Phe Leu Asp Ser S515 520 525 C Arg Gly Val Ala Met Val Leu Ala Val Gly Phe Leu Pro Phe Leu Thr 530 535 540 Ser Val Thr Leu Cys Phe Gly Leu Ile Ala Leu Trp Ser Lys Gly Lys 545 550 555 560 Gly Arg Val Lys His His Met Thr Phe Asp Phe Val Ala Pro Arg Pro 565 570 575 Ser Gly Asp Lys Asn Ser Gly Gly Asn Arg Val Thr Ala Lys Leu Phe 580 585 590 <210> <211> 142 <212> PRT <213> homo sapiens <400> Met Ala Arg Tyr Met Leu Leu Leu Leu Leu Ala Val Trp Val Leu Thr 1 5 10 Gly Glu Leu Trp Pro Gly Ala Glu Ala Arg Ala Ala Pro Tyr Gly Val 25 Arg Leu Cys Gly Arg Glu Phe Ile Arg Ala Val Ile Phe Thr Cys Gly 40 Gly Ser Arg Trp Arg Arg Ser Asp Ile Leu Ala His Glu Ala Met Gly 55 Asp Thr Phe Pro Asp Ala Asp Ala Asp Glu Asp Ser Leu Ala Gly Glu 70 75 Leu Asp Glu Ala Met Gly Ser Ser Glu Trp Leu Ala Leu Thr Lys Ser 90 Pro Gin Ala Phe Tyr Arg Gly Arg Pro Ser Trp Gin Gly Thr Pro Gly 100 105 110 Val Leu Arg Gly Ser Arg Asp Val Leu Ala Gly Leu Ser Ser Ser Cys 115 120 125 Cys Lys Trp Gly Cys .Ser Lys Ser Glu Ile Ser Ser Leu Cys 130 135 140 <210> 56 <211> 230 <212> PRT <213> homo sapiens 36/79 <400> 56 Met Ser Glu Giu Val Thr Tyr Ala Thr Leu Thr Phe Gin Asp Ser Ala 1 5 10 o Gly Ala Arg Asn Asn Arg Asp Giy Asn Asn Leu Arg Lys Arg Gly His 0 20 25 30 Pro Ala Pro Ser Pro Ile Trp Arg His Ala Ala Leu Gly Leu Val Thr 40 Leu Cys Leu Met Leu Leu Ile Gly Leu Val Thr Leu GJ.y Met Met Phe 55 Leu Gin Ile Ser Asn Asp Ile Asn Ser Asp Ser Glu Lys Leu Ser Gin 70 75 IND Leu Gin Lys Thr Ile Gin Gin Gin Gin Asp Asn Leu Ser Gin Gin Leu 90 Gly Asn Ser Asn Asn Leu Ser Met Giu Giu Giu Phe Leu Lys Ser Gin .100 105 110 Ile Ser Ser Leu Leu Lys Arg Gin Giu Gin Met Aia lie Lys Leu Cys 115 120 125 Gin Giu Leu Ile Ile His Thr Ser Asp His Arg Cys Asn Pro Cys Pro 130 135 140 Lys Met Try Gin Trp Tyr Gin Asn Ser Cys Tr Tyr Phe Thr Thr Asn 145 150 155 160 Glu Giu Lys Thr Trp Ala Asn Ser Arg Lys Asp Cys Ile Asp Lys Asn 165 170 175 Ser Thr Leu Val Lys Ile Asp Ser Leu Giu Giu Lys Asp Phe Leu Met 180 185 190 Ser Gin Pro Leu Leu Met Phe Ser Phe Phe Trp Leu Gly Leu Ser Trp 195 200 205 Asp Ser Ser Gly Arg Ser Trp Phe Trp Glu Asp Gly Ser Val Pro Ser 210 215 220 Pro Ser Leu Tyr Val Ser 225 230 <210> 57 <211> 194 <212> PRT <213> homo sapiens <400> 57 Met Trp Leu Ser Pro Ala Leu Leu Leu Leu Ile Leu Pro Gly Tyr Ser 1 5 10 Ile Ala Ala Lys Ile Thr Gly Pro Thr Thx Val Asn Gly Ser Giu Gin 25 Gly Ser Leu Thr Val Gin Cys Ala Tyr Gly Ser Gly Trp Giu Thr Tyr 40 Leu Lys Trp Arg Cys Gin Gly Ala Asp Trp Asn Tyr Cys Asn Ile Leu 55 Val Lys Thx Asn Gly Ser Giu Gin Giu Val Lys Lys Asn Arg Val Ser 70 75 Ile Axg Asp Asn Gin Lys Asn His Met Phe Thr Vai Thr Met Giu Asn 90 Leu Lys Arg Asp Asp Ala Asp Ser Tyr Trp Cys Gly Thr Giu Arg Pro 100 105 110 Gly Ile Asp Leu Gly Val Lys Val Gin Val Thr Ile Asn Pro Gly Thr 115 120 125 Gin Thr Ala Val Ser Giu Trp Thr Thr Thr Thr Ala Ser Leu Ala Phe 130 135 140 Thr Ala Ala Ala Tlr Gin Lys Thr Ser Ser Pro Leu Thr Arg Ser Pro 37,79 145 150 155 160 Leu Lys Ser Thx His Phe Leu Phe Leu Phe Leu Leu Giu Leu Pro Leu 165 170 175 Leu Leu Ser Met Leu GJy Thr Val Leu Trp Vai Asn Arg Pro Gin Arg 180 185 190 Arg Ser <210> 58 <211> 333 <212> PRT <213> homo sapiens <400> 58 Met 1 Ile Asn Lys Gly Lys Pro Gly Asp Leu 145 Gly Vai Ile Thr Lys 225 Phe Val Ile Gly Val 305 Arg Asn Pro Gly Lys Val Gly Leu Val 130 Gly Pro Arg Gly Val 210 Ile Thr Phe Leu Gly 290 Thr lie Trp Ser Gin Gly His Asp Lys Asp Gly Glu Ala Lys His 100 Arg Gly 115 Gly Pro Pro Thr Lys Gly Gly Ile 180 Glu Thr 195 Leu Ser Leu Tyr Cys His Ser Arg 260 His Thr 275 Ile Val Gly Gly Trp S Asp Asn Gly Thr Lys Gly Glu Thr Gly Glu 165 Arg Leu Lys Asn Ile 245 Asn Lys Leu Glu Leu Thr Gly Asp Ser 70 Gly Pro Thr Gly Leu 150 Ala Gly Vai Phe Glu 230 Ala Val Asp Gin Arg 310 Leu Leu Cys Arg Leu Pro 40 Ala Gly 55 Gly Glu Ile Lys Lys Gly Gly Pro 120 Pro Glu 135 Pro Gly Gly Pro Trp Lys Leu Pro 200 Pro Ser 215 Phe Asn Gly Vai Gin Vai Ala Tyr 280 Leu Lys 295 Phe Asn Ala Gin 25 Gly Glu Lys Gly Leu 105 Gin Gly Pro Thr Gly 185 Lys Ser His Tyr Ser 265 Met Leu Gly Ile 10 Gly Arg Pro Gly Asp 90 Ala Gly Pro Met Gly 170 Asp Ser Asp Tyr Tyr 250 Leu Ser Gly Leu Glu His Asp Gly Glu 75 Gin Gly Gin Arg Gly 155 Pro Arg Ala Met Asp 235 Phe Val Ser Asp Phe 315 Ser Ile Pro Gly Arg Arg Gly Pro Lys Gly 140 Pro Gin Gly Phe Pro 220 Thr Thr Lys Glu Glu 300 Ala Ser Cys Gly Arg Pro Gly Ser Met Gly 125 Asn Ile Gly Glu Thr 205 Ile Ala Tyr Asn Asp 285 Val Asp Pro Thr Ile Asp Gly Ala Arg Gly 110 Asn Ile Gly Glu Lys 190 Val Lys Ala His Gly 270 Gin Trp Glu Gly Pro Gly Ser Asp Gly Glu Lys Gly Lys Pro 175 Gly Gly Phe Gly Ile 255 Vai Ala Leu Asp Asn Gly Ala Pro Gly Ser Lys Gly Pro Pro 160 Gly Lys Leu Asp .Lys 240 Thr Lys Ser Gin Asp 320 Asp Thr Thr Phe Thr Giy Phe Leu Leu Phe 325 330 38,79 <210> 59 <211> 225 <212> PRT <213> homo sapiens <400> 59 Met 1 Ile Asn L~ys Gly Glu Thr Ile Ala Tyr 145 Asn Asp Val Asp Pro 225 Arg Asn Pro Gly Glu Lys Val Lys Ala 130 His Gly in Trp Glu 210 Ile Ser Gly Asp Pro Gly Gly Phe 115 Gly Ile Val Ala Leu 195 Asp Trp Gin His Lys Gly Lys Leu 100 Asp Lys Thr Lys Ser 180 Gin Asp Trp 5 Asp Asn Gly Val Ile Thx Lys Phe Val Ile 165 Gly Val Asp Leu Cys Leu Ala 55 Gly Glu Leu Leu Cys 135 Ser His Ile Gly Thr 215 Leu Ala Arg Gin 25 Pro. Gly 40 Gly Glu Ie Arg Thr Leu Ser Lys 105 Tyr Asn 120 His Ile Arg Asn Thr Lys Val Leu 185 Gly Glu 200 Phe Thr Ile 10 Gly Arg Ala Gly Val 90 Phe Glu Ala Val Asp 170 Gin Arg Gly Glu His Asp Gly Trp 75 Leu Pro Phe Gly Gin 155 Ala Leu Phe Phe Ile Pro Gly Pro Lys Pro Ser Asn Val 140 Val Tyr Lys Asn Leu 220 Gys Gly Arg Thr Gly Lys Ser His 125 Tyr Ser Met Leu Gly 205 Leu Thr Ile Asp Gly Asp Ser Asp 110 Tyr Tyr Leu Ser Gly 190 Leu Phe Gly Pro Gly Pro Arg Ala Met Asp Phe Val Ser 175 Asp Phe Ser Asn Gly Ala Gin Gly Phe Pro Thr Thr Lys 160 Glu Glu Ala Ser <210> <211> 205 <212> PRT <213> homo sapiens <400> Met Met Arg Thr Leu 1 5 Pro Gin Gin Leu Leu Phe Asp Phe Pro Glu Glu Lys Phe Phe Ser Val Lys Arg Arg Val Glu Tyr Cys Asn His Arg Trp Val Ala Glu 100 Gin Lys Ile Cys Tyr Ile Gin Glu Thr Leu 70 Glu His Asn Thr Leu Asp Gly 55 Ile Ile Tyr Arg Thr Val Lys 40 Pro Glu Met Phe Phe Hie Glr 25 LY Alr Pr Gl1 Le 10! Va 5 Pro 10 -i Phe s Glu Arg o Gly e' Lys 90 u Leu 5 1 Pro 39n9 Leu Gin Glu Pro Met 75 Asn Met Cys Pro Glu Phe Pro Pro Val Gln Lys Leu Val Glu Thr Leu Tyr Tyr Asn Leu Leu Asp Thr Glu Cys Lys Glu Asn His Tyr Lys Asp Glu 110 Gly Ile Leu Asp Leu Lys Ile His Leu Arg Lys Thr 2145 Lys Axg Ser Cys 130 Giu Gly Ile Phe 115 Asn Ala Tyr Pro Leu 195 Arg Ser Lys Gly 135 Phe Giu Ile Pro 150 Val. Leu Ile Thr 165 His Thr Ile Asn 180 Ser Glu Asp Gly 120 Leu Val. Glu Gly Val 140 Ala Cys Lys Tyr Giu 155 Cys Ser Trp Gin Asn 170 Asp Leu Val Giu Pro 185 Val. Phe Val Ile Ser 200 12 Tyr Ser G lx Pro Pro 205 Cys Asn Leu Leu Tyr Arg 160 Met Gin Lys 175 Giu His Arg 190 <210> 61 <211> PRT <213> homo sapiens <400> 61 Met Giu Val Val Leu 1 5 Leu Ala Asp Ala Val Asp Tyr Gin Thr Leu Phe Ser Ile Gly Ile Phe Asfl Gin Lys Pro Asn Leu Ile Thr Ala Ile Giu Arg Leu Arg 70 Asn Phe Arg Ile Leu 55 Thr Ala Leu Cys Giu Lys 25 Arg Gly 40 Ile Leu Pro Giy Thr Lys Ser Leu Gin Ile Leu Vai Gly Cys Giu Giu 75 Leu Gin 90 Leu Asp Cys Arg Giu Lys Ala Pro Ala Cys Ala Ala His Phe Val. Lys Gin Giu Ile Vai His Tyr Val Leu Cys Ser Val Gixi Ser <210> 62 <22.2> 595 <212> PRT <213> homo sapiens <400> 62 Met Glu Val Gly Met Gly Cys Trp Ala Arg Gixi Val Leu Vai Pro Giu 1 Gly Pro Lexi Val Thr Giy Tyr Arg Pro Asp Thr Gin Giu Val Gin Ala Arg Leu Ser Thr Asp 115 Arg Val Leu 130 Arg Gly Arg 145 5 Tyr Arg Val Tryr Giu Gly Giu Aia Pro Phe Ser Tyr 70 Val Gin Arg Gin Aia Gin 100 Thr Arg Tyr Pro Asp Val Gin Ala Pro 150 Ala Pro Asp 55 Ala Lexi Asp Leu Leu 135 Thx Gly Ala 40 Thr Val Gin Ala Gly 120 Gin Ser Thr 25 Gin Ala Phe Gi-. G11 101 Se3 Va Pr Ala *Leu Lys Asp 90 L Ser oPro 40/79 lai !.sn Giy Ser 75 Ser Ala Arg 155 Ser Phe Ile Arg Val Giu Gly Ala 140 Met Ile Glu Vai Val Vai Cys Lys 125 Pro Thr Ser Trp Ser Val Lexi His 110 Vai Pro Val Cys Phe Thr Ala Lys Tltr Giu Gly His Asn Leu Lys Gly so Ile Pro Leu Pro Giu 160 Gly Gin Glu Leu Ala Leu Gly Cys Leu Ala Arg Thr Ser Thr Gin Lys 165 170 175 His Thr His Leu Ala Val Ser Phe Gly Arg Ser Val Pro Glu Ala Pro CK 180 185 190 o Val Gly Arg Ser Thr Leu Gin Glu Val Val Gly Ile Arg Ser Asp Leu 0 195 200 205 Ala Val Glu Ala Gly Ala Pro Tyr Ala Glu Arg Leu Ala Ala Gly Glu D 210 215 220 Leu Arg Leu Gly Lys Glu Gly Thr Asp Arg Tyr Arg Met Val Val Gly 225 230 235 240 Gly Ala Gin Ala Gly Asp Ala Gly Thr Tyr His Cys Thr Ala Ala Glu 245 250 255 STrp Ile Gin Asp Pro Asp Gly Ser Trp Ala Gin Ile Ala Glu Lys Arg 260 265 270 c Ala Val Leu Ala His Val Asp Val Gin Thr Leu Ser Ser Gin Leu Ala C<1 275 280 285 SVal Thr Val Gly Pro Gly Glu Arg Arg lie Gly Pro Gly Glu Pro Leu 290 295 300 O Glu Leu Leu Cys Asn Val Ser Gly Ala Leu Pro Pro Ala Gly Arg His 305 310 315 320 Ala Ala Tyr Ser Val Gly Trp Glu Met Ala Pro Ala Gly His Leu Gly 325 330 335 Pro Gly Arg Leu Val Ala Gin Leu Asp Thr Glu Gly Val Gly Ser Leu 340 345 350 Gly Pro Gly Tyr Glu Gly Arg His Ile Ala Met Glu Lys Val Ala Ser 355 360 365 Arg Thr Tyr Arg Leu Arg Leu Glu Ala Ala Arg Pro Gly Asp Ala Gly 370 375 380 Thr Tyr Arg Cys Leu Ala Lys Ala Tyr Val Arg Gly Ser Gly Thr Arg 385 390 395 400 Leu Arg Glu Ala Ala Ser Ala Arg Ser Arg Pro Leu Pro Val His Val 405 410 415 Arg Glu Glu Gly Val Val Leu Glu Ala Val Ala Trp Leu Ala Gly Gly 420 425 430 Thr Val Tyr Arg Gly Glu Thr Ala Ser Leu Leu Cys Asn Ile Ser Val 435 440 445 Arg Gly Gly Pro Pro Gly Leu Arg Leu Ala Ala Ser Trp Trp Val Glu 450 455 460 Arg Pro Glu Asp Gly Glu Leu Ser Ser Val Pro Ala Gin Leu Val Gly 465 470 475 480 Gly Val Gly Gin Asp Gly Val Ala Glu Leu Gly Val Arg Pro Gly Gly 485 490 495 Gly Pro Val Ser Val Glu Leu Val Gly Pro Arg Ser His Arg Leu Arg 500 505 510 Leu His Ser Leu Gly Pro Glu Asp Glu Gly Val Tyr His Cys Ala Pro 515 520 525 Ser Ala Trp Val Gin His Ala Asp Tyr Ser Trp Tyr Gln Ala Gly Ser 530 535 540 Ala Arg Ser Gly Pro Val Thr Val Tyr Pro Tyr Met His Ala Leu Asp 545 550 555 560 Thr Leu Phe Val Pro Leu Leu Val Gly Thr Gly Val Ala Leu Val Thr 565 570 575 Gly Ala Thr Val Leu Gly Thr Ile Thr Cys Cys Phe Met Lys Arg Leu 580 585 590 Arg Lys Arg 595 <210> 63 41/79 L C n <211> 613 <212> PRT <213> homo sapiens S<400> 63 O Met Gly Ala Leu Arg Pro Thr Leu Leu Pro Pro Ser Leu Pro Leu Leu 1 5 10 N Leu Leu Leu Met Leu Gly Met Gly Cys Trp Ala Arg Glu Val Leu Val 25 Pro Glu Gly Pro Leu Tyr Arg Val Ala Gly Thr Ala Val Ser Ile Ser 40 IN) Cys Asn Val Thr Gly Tyr Glu Gly Pro Ala Gin Gin Asn Phe Glu Trp 50 55 Phe Leu Tyr Arg Pro Glu Ala Pro Asp Thr Ala Leu Gly Ile Val Ser CK1 65 70 75 1 Thr Lys Asp Thr G1n Phe Ser Tyr Ala Val Phe Lys Ser Arg.Val Val 90 Ala Gly Glu Val Gin Val Gin Arg Leu Gin Gly Asp Ala Val Val Leu 100 105 110 Lys Ile Ala Arg Leu Gin Ala Gin Asp Ala Gly Ile Tyr Glu Cys His 115 120 125 Thr Pro Ser Thr Asp Thr Arg Tyr Leu Gly Ser Tyr Ser Gly Lys Val 130 135 140 Glu Leu Arg Val Leu Pro Asp Val Leu Gin Val Ser Ala Ala Pro Pro 145 150 155 160 Gly Pro Arg Gly Arg Gin Ala Pro Thr Ser Pro Pro Arg Met Thr Val 165 170 175 His Glu Gly Gin Glu Leu Ala Leu Gly Cys Leu Ala Arg Thr Ser Thr 180 185 190 Gin Lys His Thr His Leu Ala Val Ser Phe Gly Arg Ser Val Pro Glu 195 200 205 Ala Pro Val Gly Arg Ser Thr Leu Gin Glu Val Val Gly Ile Arg Set 210 215 220 Asp Leu Ala Val Glu Ala Gly Ala Pro Tyr Ala Glu Arg Leu Ala Ala 225 230 235 240 Gly Glu Leu Arg Leu Gly Lys Glu Gly Thr Asp Arg Tyr Arg Met Val 245 250 255 Val Gly Gly Ala Gin Ala Gly Asp Ala Gly Thr*Tyr His Cys Thr Ala 260 265 270 Ala Glu Trp Ile Gin Asp Pro Asp Gly Ser Trp Ala Gin Ile Ala Glu 275 280 285 Lys Arg Ala Val Leu Ala His Val Asp Val Gin Thr Leu Ser Ser Gin 290 295 300 Leu Ala Val Thr Val Gly Pro Gly Glu Arg Arg Ile Gly Pro Gly Glu 305 310 315 320 Pro Leu Glu Leu Leu Cys Asn Val Ser Gly Ala Leu Pro Pro Ala Gly 325 330 335 Arg His Ala Ala Tyr Ser Val Gly Trp Glu Met Ala Pro Ala Gly Ala 340 345 350 Pro Gly Pro Gly Arg Leu Val Ala Gin Leu Asp Thr Glu Gly Val Gly 355 360 365 Ser Leu Gly Pro Gly Tyr Glu Gly Arg His Ile Ala Met Glu Lys Val 370 375 380 Ala Ser Arg Thr Tyr Arg Leu Arg Leu Glu Ala Ala Arg Pro Gly Asp 385 390 395 400 Ala Gly Thr Tyr Arg Cys Leu Ala Lys Ala Tyr Val Arg Gly Ser Gly 405 410 415 Thr Arg Leu Arg Glu Ala Ala Ser Ala Arg Ser Arg Pro Leu Pro Val 420 425 430 42/79 His Gly Ser ,465 Val Val Gly Leu Ala 545 Gly Leu Val Arg Val Gly 450 Val Glu Gly Gly Arg 530 Pro Ser Asp Thr Leu 610 Arg 435 Thr Arg Arg Gly Gly 515 Leu Ser Ala Thr Gly 595 Arg Glu Val Gly Pro Val 500 Pro His Ala Arg Leu 580 Ala Lys Glu Tyr Gly Glu 485 Gly Val Ser Trp Ser 565 Phe Thr Arg Gly Arg Pro 470 Asp Gin Ser Leu Val 550 Gly Val Val Val Gly 455 Pro Gly Asp Val Gly 535 Gin Pro Pro Leu Val 440 Glu Gly Glu Gly Glu 520 Pro His Val Leu Gly 600 Glu Ala Arg Ser 490 Ala Val Asp Asp Val 570 Val Ile Ala Ser Leu 475 Ser Glu Gly Glu Tyr 555 Tyr Gly Thr Val Ala 445 Leu Leu 460 Ala Ala Val Pro Leu Gly Pro Arg 525 Gly Val 540 Ser Trp Pro Tyr Thr Gly Cys Cys 605 Trp Cys Ser Ala Val 510 Ser Tyr Tyr Met Val 590 Phe Leu Asn Trp Gin 495 Arg His His Gin His 575 Ala Met Ala Ile Trp 480 Leu Pro Arg Cys Ala 560 Ala Leu Lys <210> 64 <211> 596 <212> PRT <213> homo sapiens <400> 64 Met Ala 1 Ser Val Ala Val Gly Tyr Ser Leu Gly Ser Ala Thx Ile Ser Gly Gly 130 Ser Val 145 Val His Leu Gly Ile Tyr Ala Asn Ala Asp Gly Ile Phe Leu Phe Ala Gly Ala Tyr Val 100 Ser Glu 115 Gin Arg Phe Thr Ile Cys Ile Thr 180 Thr Asp 195 Ser 5 Ile Trp Ala Ser Ala Leu Ile Ile Lys Leu 165 Ala Ala Thr Ser Asp Leu His Tlr Pro Gly Thr Gin Leu Ile Ser Gly Ser 70 Gly Leu Val Arg Ile 150 Gly Leu Leu Val Ser Arg 55 Glu Gly Ala Thr Met 135 Ser Trp Tyr Gin Ile Cys 40 Asp Gly Leu Leu Leu 120 Tyr Leu Asn Thr Thr 200 Thr 25 Arg Met Ser Ala Ala 105 Pro Leu Asp Phe Ile 185 Leu 10 Val Ala Thr Gly Vai 90 Trp Glu Ser Leu Tyr 170 Ala Ile Tyr Ser Trp Leu 75 Ala Val Tyr Val Tyr 155 Leu Gly Met Phe Arg Trp Phe Gly Phe Ile Leu 140 Ala Ser Gly Val Ala Asn Pro Ile Phe Val Gin 125 Ser Gly Thr Ieu Val 205 Leu Asn Thr Vai Ile Gly Gly Leu Glu Trp Pro Ile 110 Lys Arg Leu Leu Ala Leu Ile Leu 175 Ala Ala 190 Gly Ala Vai Asn Ala Ala Asn Tyr Tyr Leu Phe 160 Thr Val Val Ile Leu Thr Ile Lys Ala Phe Asp Gin Ile Gly Gly Tyr Gly Gin Leu 43,79 210 Gin Ala Ala Tyr Ala Gin Ala Ilie Pro Ser Arg Thr Ile Ala Asn Thr Thr Cys His His Thr Gly Met Ala Thr 275 Leu Ser Ala 290 Ser Tyr Leu 305 Ile Ser Arg Glu Cys Leu Tyr Pro Lys 355 Met Ile Aia 370 Phe Asn Ser 385 Arg Pro Arg Ile Val Ala Asp Ser Asn 435 Ser Leu Ala 450 Arg Arg Ala 465 Val Val Gly Pro Cys Gl.y Tyr Len His 51E Val Ala G11 530 Asn Leu Th2 545 Ala Gly Asl Cys Gly Phi Ala Tyr phi 59! Leu Pro 245 Asp Len 260 Trp, Tyr Arg Asp Lys Met Ala Leu 325 Arg Ala 340 Len Val Val Met Ser Ser Ser Gly 405 Le Ile 420 Ser Gly Pro Pro Asn Gin 'Ala Thr 485 GJlu Pro 500 Phe Ala rSer Len -Trp, Trp Gly Gin 565 a Asn Ala 580 B Ala rg 'I ?ro rrp( en eu 310 Phe Cys Met Leu Thr 390 Giu Gly Gin Val Gin 470 Arg Asp Val Leu Thr 550 Thr ~hr Prp -ys ksn 295 Pro Pro Gly Gin Ala 375 Leu Arg Val Len Thr 455 Gly Len Thx Ala Thr 535 Leu Pro Asp Thx Thr 280 His Met Asp Ala Len 360 Ala Phe Gin Ser Phe 440 Ala Ala Val Arg Leu 520 Pro IAla Glr Ala P. Gly 1 265 Asp Ala Giy] Asp Gin 345 Met Len Thr Len Val 425 Ile Val Phe Len Pro 505 Phe Pro Gin 1Lys let so0 let iln eu Zfal. 330 Val Pro Met Met Len 410 Ala Tyr Phe Trp Gin 490 Ala Ala Pro ASI Hi E 235 His b Thr Val Ala Ile 315 Gly Gly Ile Ser Asp 395 Len Trp Met Val Giy 475 Phe Val Leu Gin Val. 555 Ala ~et ?he Ie 300 Ile Cys Gly Ser 380 Ile Val le Gin Len 460 Len Len Len Ser Ser 540 Pro Phe Phe Gly I Val C 285 Ser Met Val Ser Len 365 Len Trp Gly Pro Ser 445 Gly Ile Asn Gly Gly 525 Val Leu Trp Lrg ~eu ;in Ie ?ro 7ai ksn 350 Arg Thr Arg Arg Val 430 Vai Vai Ala Pro Ser Ala Gir Glj Al~ 2 Asp P 255 Thr I Arg Len I~ Gly b Pro 335 Gly Ser Arg Leu 415 Len Thr Phe Gly Ala 495 Ile Val .le Thr i Arg 575 'ro lie ~er lia let 320 ;,er Leu Ile Leu 400 Val. Gin Ser Trp, Len 480 Pro His Val Gin Lys 560 Val 570 Ile Leu Len Met 585 Cys Val Asn Ile Phe Phe Tyr 590 <210> <211> 393 <212> PRT <213> homo sapiens <400> Met Asp Ser Len Lys Asn Gin Asn Tyr Asp Len Val Phe Val Gin Ala 1 5 10 44p9 ln Phe Asp Phe Cys Ser Phe Leu Ile Ala Glu Lys Leu Val Lys Pro Phe 25 0 Val Ala Ile Leu Pro Thr Thr Phe Gly Ser Leu Asp Phe Gly Leu Pro C1 35 40 Ser Pro Leu Ser Tyr Val Pro Val Phe Pro Ser Leu Leu Thr Asp His 55 O Met Asp Phe Trp Gly Arg Val Lys Asn Phe Leu Met Phe Phe Ser Phe \C 65 70 75 SSer Arg Ser Gin Trp Asp Met Gin Ser Thr Phe Asp Asn Thr Ile Lys 90 Glu His Phe Pro Glu Gly Ser Arg Pro Val Leu Ser His Leu Leu Leu S100 105 110 IN Lys Ala Glu Leu Trp Phe Val Asn Ser Asp Phe Ala Phe Asp Phe Ala c 115 120 125 Arg Pro Leu Leu Pro Asn Thr Val Tyr Ile Gly Gly Leu Met Glu Lys S130 135 140 l Pro Ile Lys Pro Val Pro Gin Asp Leu Asp Asn Phe Ile Ala Asn Phe 145 150 155 160 SGly Asp Ala Gly Phe Val Leu Val Ala Phe Gly Ser Met Leu Asn Thr S165 170 175 His Gin Ser Gln Glu Val Leu Lys Lys Met His Asn Ala Phe Ala His 180 185 190 Leu Pro Gin Gly Val Ile Trp Thr Cys Gin Ser Ser His Trp Pro Arg 195 200 205 Asp Val His Leu Ala Thr Asn Val Lys Ile Val Asp Trp Leu Pro Gin 210 215 220 Ser Asp Leu Leu Ala His Pro Ser Ile Arg Leu Phe Val Thr His Gly 225 230 235 240 Gly Gin Asn Ser Val Met Glu Ala Ile Arg His Gly Val Pro Met Val 245 250 255 Gly Leu Pro Val Asn Gly Asp Gin His Gly Asn Met Val Arg Val Val 260 265 270 Ala Lys Asn Tyr Gly Val Ser Ile Arg Leu Asn Gin Val Thr Ala Asp 275 280 285 Thr Leu Thr Leu Thr Met Lys Gin Val Ile Glu Asp Lys Arg Tyr Lys 290 295 300 Ser Ala Val Val Ala Ala Ser Val Ile Leu His Ser Gin Pro Leu Ser 305 310 315 320 Pro Ala Gin Arg Leu Val Gly Trp Ile Asp His Ile Leu Gin Thr Gly 325 330 335 Gly Ala Thr His Leu Lys Pro Tyr Ala Phe Gin Gin Pro Trp His Glu 340 345 350 Gin Tyr Leu Ile Asp Val Phe Val Phe Leu Leu Gly Leu Thr Leu Gly 355 360 365 Thr Met Trp Leu Cys Gly Lys Leu Leu Gly Val Val Ala Arg Trp Leu 370 375 380 Arg Gly Ala Arg Lys Val Lys Lys Thr 385 390 <210> 66 <211> 523 <212> PRT <213> homo sapiens <400> 66 Met Val Gly Gin Arg Val Leu Leu Leu Val Ala Phe Leu Leu Ser Gly 1 5 10 Val Leu Leu Ser Glu Ala Ala Lys Ile Leu Thr Ile Ser Thr Leu Gly 45/79 Gly Ser His Tyr 25 Arg Leu Leu Leu Asp Val Ser Gin Ile Leu Gin Glu His G Pro A Ser P Ile G Leu M Asp I I Glu 2 145 Pro I Leu I Asp I Ser I Ile I 225 Leu I Phe Glu Asn Asn 305 Ala Pro Pro His Met 385 Val Ala Tyr Leu Thr 465 ly 0 sp ro lu [et :le .30 la 'he )ro lis ?he 210 -ys Leu Ala Lys Phe 290 Thr His Arc Glr G1 37( Va Va As Ly Se G' His Ile Glu Thr Glu 115 Met Phe Val Ser Met 195 Ser Glu Lys Arg Pro 275 Gl His Let AsI 1 Se r Gil L Gil L Al p Th- s Se 43 r Pr 0 y Gi Asn V Lys G Asp H 8 Ala L 100 Ile P Asp S Asp P Ala I 1 Pro 1 180 Asp I Arg His I Ala Pro 260 Ile Asp Gin Pro Val 340 Asp 5 Gin y Leu Lys r Leu 420 r Ala 5 o Ala y Ala al lu .is 5 eu 'he er he :le 65 .eu ?he 3er Phe 3lu 245 Leu Lys Ala Ser Glr 325 His Lei Asi Pr As Th Va. G1: Th Thr Glu 70 Gin Asp Gly Leu ys 150 Leu Ser Trp Gin Pro 230 Leu Leu Pro Gi) Glir 31( I Gil Lei 1 Lei i Se: 0 Va 39 .i Ty 5 r Le 1 Va n Ar r Hi 47 Met L 55 Glu L Lys A Gly A Thr G 1 Lys A 135 Ser P Pro I Tyr V Gly .Z Trp .Z 215 Glu Trp I Pro I Val r Phe 295 1 Glu I Val i Ala .i Ala r Val 375 1 Asn 0 r Gly u Thr 1 Ala g Leu 455 s Leu 0 eu ys rg rg in 20 sn 'he 'hx ral !00 sp ;ly ?he ksn Prc 28 V~al Va) ~11 Ils Thn Hi 361 Me G1 Va Me Al 44 Va Ly His G Ser T Ile L 9 Lys G 105 Cys S Glu; Leu I Thr I Pro T 185 ValI Met Ser Val LThr' 265 Gin. Leu L Leu B Trp c Asn 345 s Pro 0 t Glu y Asp 1 Ser t Lys 425 a Ser 0 1 Gly s Pro in lyr ys 0 lu er LSn :le !he .70 Tal ys 31n k~rg Asn 250 Val Asp Val Lys Thi 33( Va Se Al G11 Ii' 41 Gi: Va Tr Ty Ser G 6 Gin V 75 Lys H Ser G Tyr L Tyr A I Ala G 155 Gly S Phe I Asn I Ser Pro 235 Ser Tyr Leu Ala Lys 315 Cys L Lys c Ile a Ile n His 395 e Arg 0 n Val 1 Ile p Ile r Ala 475 4 ly L 0 a. I is P iu A eu L I ,sp L liu I ;er I ,ro 5 ?he I PhrI lal I ksp Ile Asp. Phe 300 Met Gin Ile Arg Arg 380 Gly Leu Ile Leu Asp 460 Phe ys le 'he la leu ieu rys .eu ;er ,eu 205 ?he Leu Phe Gly Asr 285 Glj His Se Va Let 36! Hi! Asl As: GI Hi 44 Hi GI Phe L Arg T: Asp S 9 Leu V 110 Ser A Val P Leu V Asp P 1 Leu L 190 Met P Asp I Ser I Ala I Gly I 270 Phe r Ser I 3 Asn Ser L Asp 350 i Phe s Gly n Met n Gin u Asp 430 s Ser s Ile n Gin eu rp er al rg he al 'he eu ,he sn is 'he eu xlet Hi 33! Trj Va. Va Va. Va. 41 Ly GI Le Pr Ile Phe Tyr Lys Lys Val Lys 160 Gly Thr Phe Thr Leu 240 Asp Met Ala Leu i Phe 320 5 Trp Leu L Thr 1 Pro 1 Arg 400 1 Thr s Arg n Pro u Gin o Trp 480 His Glu Gin Tyr Leu Ile 485 Asp Val Ph e Val 490 46/79 Phe Leu Leu Gly Leu Thx 495 Leu Gly Thr Met Trp Leu Cys Gly Lys Leu Leu Gly Val Val Ala Arg 500 505 510 Trp Leu Arg Gly Ala Arg Lys Val Lys Lys Thr 515 520 <210> 67 <211> 252 <212> PRT <213> homo sapiens <400> 67 Met 1 Val Glu Arg Lys Thr Cys Asn Gin Glu 145 His Val Ala Glu Tyr 225 Thr Ser Cys Leu Ala Leu Trp Ile Leu Ser 130 Cys Tyr Asn Val Ala 210 Gly Pro Cys Gly Leu Ile Arg Asp Trp Gly 115 Trp Asn Thr Thr Tyr 195 Pro Gly Asn Val Ser Ser Pro Gly Asp Glu 100 Ala Tyr Pro Gin Cys 180 Phe Tyr Ser Thr Leu 5 Gin Lys Arg Gin Glu His His Asp Trp Ile 165 Arg Val Lys Cys Phe 245 Gly Gly Tyr Glu Val 70 Leu Gly Trp Glu Cys 150 Val Lys Cys Asn Arg 230 Ala Gly Tyr Gin Asp 55 Gin Glu Pro Gly Val 135 Pro Trp Met Asn Gly 215 Asn Val Leu His 40 Lys Pro Lys Thx Arg 120 Lys Glu Ala Thr Tyr 200 Arg Asn Ile Leu 25 Asn Glu Gin Ser Ser 105 Tyr Asp Arg Thr Val 185 Ser Pro Leu Pro 10 Pro Glu Glu Ala Ala 90 Leu Arg Tyr Cys Thr 170 Trp Pro Cys Cys Leu Asn Ser Ile Ser 75 Ala Leu Ser Thr Ser 155 Asn Gly Lys Ser Tyr 235 Gly Val His Leu Asn Ala Val Pro Tyr 140 Gly Lys Glu Gly Glu 220 Arg Leu Thr Ser Met Met Trp Ser Gly 125 Pro Pro Ile Val Asn 205 Cys Gly Leu Leu Arg Leu Glu Ala Ile 110 Phe Tyr Met Gly Trp 190 Trp Pro Arg Phe Leu Val His Tyr Ser Gly His Pro Cys Cys 175 Glu Ile Pro Lys Leu Glu Arg Asn Met Gin Gin Val Ser Thr 160 Ala Asn Gly Ser Phe 240 Met Asn Leu Pro Ser Vai 250 <210> 68 <211> 497 <212> PRT <213> homo sapiens <400> 68 Met Ser Cys Val Leu Gly Giy Val Ile Pro Leu Gly Leu Leu Phe Leu 1 5 10 Val Cys Gly Ser Gin Giy Tyr Leu Leu Pro Asn Val Thr Leu Leu Glu 25 Glu Leu Leu Ser Lys Tyr Gin His Asn Giu Ser His Ser Arg Vai Arg 40 Arg Ala Ile Pro Arg Giu Asp Lys Giu Giu Ile Leu Met Leu His Asn 47n9 n 50 55 SLys Leu Arg Gly Gin Val Gin Pro Gin Ala Ser Asn Met Glu Tyr Met 70 75 Thr Trp Asp Asp Glu Leu Glu Lys Ser Ala Ala Ala Trp Ala Ser Gin o 85 90 O Cys Ile Trp Glu His Gly Pro Thr Ser Leu Leu Val Ser Ile Gly Gin 100 105 110 NO Asn Leu Gly Ala His Trp Gly Arg Tyr Arg Ser Pro Gly Phe His Val 115 120 125 Gin Ser Trp Tyr Asp Glu Val Lys Asp Tyr Thr Tyr Pro Tyr Pro Ser 130 135 140 n Glu Cys Asn Pro Trp Cys Pro Glu Arg Cys Ser Gly Pro Met Cys Thr 145 150 155 160 His Tyr Thr Gin Ile Val Trp Ala Thr Thr Asn Lys Ile Gly Cys Ala C(K 165 170 175 CO Val Asn Thr Cys Arg Lys Met Thr Val Trp Gly Glu Val Trp Glu Asn 180 185 190 SAla Val Tyr Phe Val Cys Asn Tyr Ser Pro Lys Gly Asn Trp Ile Gly 195 200 205 Glu Ala Pro Tyr Lys Asn Gly Arg Pro Cys Ser Glu Cys Pro Pro Ser 210 215 220 Tyr Gly Gly Ser Cys Arg Asn Asn Leu Cys Tyr Arg Glu Glu Thr Tyr 225 230 235 240 Thr Pro Lys Pro Glu Thr Asp Glu Met Asn Glu Val Glu Thr Ala Pro 245 250 255 Ile Pro Glu Glu Asn His Val Trp Leu Gin Pro Arg Val Met Arg Pro 260 265 270 Thr Lys Pro Lys Lys Thr Ser Ala Val Asn Tyr Met Thr Gin Val Val 275 280 285 Arg Cys Asp Thr Lys Met Lys Asp Arg Cys Lys Gly Ser Thr Cys Asn 290 295 300 Arg Tyr Gin Cys Pro Ala Gly Cys Leu Asn His Lys Ala Lys Ile Phe 305 310 315 320 Gly Thr Leu Phe Tyr Glu Ser Ser Ser Ser lie Cys Arg Ala Ala Ile 325 330 335 His Tyr Gly Ile Leu Asp Asp Lys Gly Gly Leu Val Asp Ile Thr Arg 340 345 350 Asn Gly Lys Val Pro Phe Phe Val Lys Ser Glu Arg His Gly Val Gin 355 360 365 Ser Leu Ser Lys Tyr Lys Pro Ser Ser Ser Phe Met Val Ser Lys Val 370 375 380 Lys Val Gin Asp Leu Asp Cys Tyr Thr Thr Val Ala Gin Leu Cys Pro 385 390 395 400 Phe Glu Lys Pro Ala Thr His Cys Pro Arg Ile His Cys Pro Ala His 405 410 415 Cys Lys Asp Glu Pro Ser Tyr Trp Ala Pro Val Phe Gly Thr Asn Ile 420 425 430 Tyr Ala Asp Thr Ser Ser Ile Cys Lys Thr Ala Val His Ala Gly Val 435 440 445 Ile Ser Asn Glu Ser Gly Gly Asp Val Asp Val Met Pro Val Asp Lys 450 455 460 Lys Lys Thr Tyr Val Gly Ser Leu Arg Asn Gly Val Gin Ser Glu Ser 465 470 475 480 Leu Gly Thr Pro Arg Asp Gly Lys Ala Phe Arg Ile Phe Ala Val Arg 485 490 495 Gin 48/79 <210> 69 <211> 438 <212> PRT <213> homo sapiens <400> 69 Asx Met 1 Asn Met Ala Trp Val Ser Pro Gly Tyr Pro Gly Pro Lys Ile Glu Val 130 Gly Asn 145 Glu Cys Arg Glu Val Glu Arg Val 210 Met Thr 225 Gly Ser Lys Ala Cys Arg Val Asp 290 Arg His 305 Met Val Ala Gin His Cys Phe Gly 370 Val His 385 Met Pro Leu Glu Ala Ile Phe Tyr Met Gly 115 Trp Trp Pro Glu Thr 195 Met Gin Thr Lys Ala 275 Ile Gly Ser Leu Pro 355 Thr Ala Val His Tyr Ser Gly Iis Pro Cys 100 Cys Glu Ile Pro Thr 180 Ala Arg Val Cys Ile 260 Ala Thr Val Lys Cys 340 Ala Asn Gly Asp Asn 5 Met Gin Gin Val Ser Thr Ala Asn Gly Ser 165 Tyr Pro Pro Val Asn 245 Phe Ile Arg Gin Val 325 Pro His Ile Val Lys 405 Lys Leu Arg Gly Gin Vai Gin Pro Gin Ala Ser 10 Thr Cys Asr Gin 70 Glu His Vai Ala Glu 150 Tyr Thr Ile Thr Arg 230 Arg Gly His Asn Ser 310 Lys Phe Cys Tyx Ile 390 Lys Trp Ile Leu 55 Ser Cys Tyr Asn Val 135 Ala Gly Pro Pro Lys 215 Cys Tyr Thr Tyr Gly 295 Leu Val Glu Lys Ala 375 Ser Lys Asp Trp 40 Gly Trp Asn Thr Thr 120 Tyr Pro Gly Lys Glu 200 Pro Asp Gin Leu Gly 280 Lys Ser Gin Lys Asp 360 Asp Asn Thr Asp 25 Glu Ala Tyr Pro Gin 105 Cys Phe Tyr Ser Pro 185 Glu Lys Thr Cys Phe 265 Ile Val Lys Asp Pro 345 Glu Thr Glu Tyr Glu Leu His Gly His Trp Asp Glu 75 Trp Cys 90 Ile Val Arg Lys Val Cys Lys Asn 155 Cys Arg 170 Glu Thr Asn His Lys Thr Lys Met 235 Pro Ala 250 Tyr Glu Len Asp Pro Phe Tyr Lys 315 Leu Asp 330 Ala Thr Pro Ser Set Set Ser Gly 395 Val Gly 410 Arg Asp lu Pro fly Val Pro rrp Met Asn 140 Gly Asn Asp Val Ser 220' Lys Gly Ser Asp Phe 300 Pro Cys His Tyr Ile 380 Gly Ser Gl? Lys Thr Arg Lys Glu Ala Thr 125 Tyr Arg Asn Glu Trp 205 Ala Asp Cys Ser Lys 285 Val Set Tyr Cys Trp 365 Cys Asp Leu Lys Ser Ser Tyr Asp Arg Thx 110 Val Ser Pro Leu Met 190 Leu Val Arg Len Ser 270 Gly Lys Set Thr Pro 350 Ala Lys Val Arg Ala Ala Leu Arg Tyr Cys Thr Trp Pro Cys Cys 175 Asn Gin An Cys Asn 255 Set Gly Ser Ser Thr 335 Arg Pro Thr Asp Asn 415 Phe Ala Leu Ser Thr Set Asn Gly Lys Ser 160 Tyr Glu Pro Tyr Lys 240 His Ile Leu Glu Phe 320 Val Ile Val Ala Val 400 Gly Arg Val Gin Set Glu Set Leu Gly Thi Pro 49/79 420 Ile Phe Ala Val Arg Gin 435 <210> <211> 308 <212> PRT <223> homo sapiens <400> Met 1 Ala I Phe Tyr Asn Asp Leu Gly. Ser Leu 145 Ala Val Ala Ala Gly 225 Tyr Pro Met Tal er ,ly ?he 31y rhr His Asp Leu 130 Val Leu Ala Asp Leu 210 Gly Gly Gly Met Gly Asp Trp Ser Ala Phe Leu Pro 115 Phe Gly Asp Ala Gin 195 Thr Glu Leu Leu Leu 275 ;iy Val Leu Ala Ser Leu Gly Phe Val Phe Ser Ala Phe jeu k1a krg Ser ly Thr 100 Pro Thr Gly Arg Met 180 Gly Gly Glu Ser Val 26C Met 5 Leu I Leu Arg Ser Trp Pro Ala Arg Gly Gly 165 Gly Trp Leu Ser Ala 245 Gly Ser iis fal krg Leu 70 Arg Cys Pro Arg Tyr 150 Leu Asp Val Gly Trp 230 Gly Val Leu Leu Tyr I 2 Phe Ala I 40 Val Leu 2 55 Leu Lou I Gly Ala Gly Ala Pro Arg 120 Ala Phe 135 Phe Val Gly Gly Ala Gly Pro Leu 200 Leu Trp 215 Gly Gly Ser Tyr Gly Gly Gly Gly .eu 55 ?ro kla kla Leu Leu 105 Ser Ser Pro Tyr Ala 185 Pro Val Pro Ala Val 265 Lei 10 Gly I Ala I Val Pro Leu 90 Leu Pro Ile Tyr Gly 170 Arg Arg Val Leu Pro 250 Val Leu eu eu aly kla 75 Leu Leu Leu Phe Val 155 Ala Leu Leu Gly Leu 235 Leu Gir Glj Gly I Gly Leu Leu Leu Pro Ala Ala 140 His Ala Val Leu Leu 220 Ala Val Ala Pro eu rhr k1a Gln 31y Leu Ala 125 Leu Leu Leu Cys Ala 205 Val Ala Phe Th Prc Leu 2 Leu Leu Leu I Ala Val 110 Leu Gly Ala Val Gly 190 Val Pro Ala Gly Gly 270 Leu la er hr .eu Ile Leu Gly Thr Pro Val 175 Trp Phe Val Val Val 255 Leu Ser Gly Arg Gly Leu Thr Pro Leu Ala His 160 Ala Leu Gly Val Ala 240 Leu Val Gly 285 Lys Asp Leu Ser Ser Gin Ile Cys Leu Gin Lou Ser Ser Ala Pro Gly 290 295 300 Val 305 Arg Gly Phe <210> 71 <211> 447 <212> PRT <213> homo sapiens <400> 71 50/79 Met Thr Pro Gin Pro Ala Gly Pro Pro Asp Gly Gly Trp Gly Trp Val 1 5 10 Val Arg Ser Gin. Arg Phe Leu Thr Ala 145 Gin Gly Leu Ala Leu 225 Leu Leu Cys Ala Val 305 Ala Phe Thr Pro Phe 385 Gly Thr Leu Ala Ser Ala Ala Pro Ser Leu Leu 130 Leu Leu Ala Val Leu 210 Gly Ala Val Gly Val 290 Pro Ala Gly Gly Leu 370 Leu Leu Pro Leu Ala Ala Leu Gly Gin Asp Ala Ser Val Val Ala Phe 100 Ala Gly 115 Ser Arg Thr Gly Leu Leu Ile Thr 180 Leu Pro 195 Gly Leu Thx Ala Pro His Val Ala 260 rrp Leu 275 Phe Gly Val Val Val Ala Val Leu 340 Leu Val 355 Ser Gly Leu Ser Pro Arg Pro Pro 420 Ser Pro 435 Ala Phe Leu Ala Thr Ala Pro Val 70 Met Val Ala Ser Phe Gly Tyr Phe Asn Gly 150 Asp Thr 165 Leu His Gly Asp Ser Leu Leu Val 230 Ala Leu 245 Val Ala Ala Asp Ala Leu Gly Gly 310 Tyr Gly 325 Pro Gly Met Met Phe Leu Gly Ser 390 Ala Leu 405 Glu Thr Ala Phe Trp 55 Gly Gly Asp Trp Ser 135 Ala Phe Leu Pro Phe 215 Gly Asp Ala Gin Thr 295 Glu Leu Leu Leu Arg 375 Leu Pro Gly Ile Pro 40 Ile Ser Gly Leu Ala 120 Arg Ser Gly Thr Pro 200 ThI Gly Arg Met Gly 280 Gly Glu Ser Val Met 360 Asp Ile Ser Glu Gly 440 Asn 25 Asp Ser Ala Val Leu 105 Leu Arg Ser Trp, Pro 185 Ala Arg Gly Gly Gly 265 Trp Leu Ser Ala Gly 345 Ser Glu Leu Cys Leu 425 Ser Gly Leu Ala Lou Leu 90 His Val Arg Leu Arg 170 Cys Pro Arg Tyr Leu 250 Asp Val Gly Trp Gly 330 Val Leu Thr Ser Gly 410 Leu Thr Leu Ala Leu Ser 75 Ala Leu Phe Val Leu 155 Gly Gly Pro Ala Phe 235 Gly Ala Pro Leu Gly 315 Ser Gly Gly Gly Gly 395 Pro Pro Leu Ser Glu Ala Thr Ser Tyr Ala Leu 140 Leu Ala Ala Arg Phe 220 Val Gly Gly Leu Trp 300 Gly Tyr Gly Gly Asp 380 Ser Ala Ala Asp Tyr( His Leu Arg Leu Leu 4 Pro 125 Ala Ala Leu eu Ser 205 Ser Pro Tyr Ala Pro 285 Val Pro Ala Val Leu 365 Phe Phe Ser Pro Thr 445 Gly Phe Ala Irp Gly Gly 110 Ala Val Pro Leu Leu 190 Pro Ile Tyr Gly Arg 270 Arg Val Leu Pro Val 350 Leu Thx Ile Pro Gin 430 Thr Leu Asp Val Gly Phe Leu Leu Gly Ala Leu 175 Leu Leu Phe Val Ala 255 Leu Leu Gly Leu Leu 335 Gin Gly Ala Tyr Pro 415 Ala Cys Leu Arg Gin Ala Val Gly Gly Leu Leu 160 Leu Pro Ala Ala His 240 Ala Val Leu Leu Ala 320 Val Ala Pro Ser Ile 400 Ala Val Gly Gly Pro <210> 72 5179 <211> 458 <212> PRT <213> hono sapiens <400> 72 Asx M 1 Val Arg I Gin 1 Gin I Arg I Leu Leu Cys Ala 145 Gin Ser Pro Thr Thr 225 His Ser Leu Thr Pro 305 Ala Arg Gly Gly Gly 385 Thr Iet A ral L ier P 3 la 2 00 ?he C ?ro kla Leu Leu 130 Leu Trp Ala Ser Ser 210 Leu Leu Val Gly Thr 290 Thr Leu Arg Gly Asn 370 Ser Thr la ,eu ,he ;5 la fly Tal 3er 3er LIS Ser rhr Leu Leu Leu 195 Leu Ile Gin Val Asp 275 Leu Ala Ala Ile Let 355 Ty3 Gil Se Arg A Ser A Gly Arg i Ser I Val b E Phe I 100 Gly Cys Gly Leu Ser 180 Ala Leu Asn Asp Ala 260 Ala Thr Leu Pro STyr 340 Leu Thx Ile SGly rg Thr Glu Pro Pro Asp Gly Gly Trp Gly Trp Val 5 la ral ~al 'ro let la 3er Eyr 7al Ser 165 Leu 31u His Thr Leu 245 Ile Val Gly Val Let 325 CyE G11 Al Let Prc Phe F Phe F Ser 1 5 Val C 70 Thr Thr Gly Phe Gly 150 His His Asp His Gly 230 Asp Ser Pro Vai Ala 310 Ala Gly Pro I Ser 1 Leu 390 Gin 'he ,he 'rp ily 3er rrp Ser 135 Leu Tyr Leu Pro Gly 215 Tyr Trp Asp Gly Ser 295 Let PhE Let Prc Phe 37 Th: As Gin S 2 Val G 40 Ile P Ser I Gly I Leu Ala I 120 Arg Ser Ala Val Ala' 200 Pro Phe Asp Leu Pro 280 Leu Ala Ser Gly Leu 360 i Val L c Leu SLeu er 55 ;lu la la Ele Phr L05 eu !Lrg 3er rrp Ala 185 Val Phe Ile Pro Val 265 Val Ala Val Val Le. 341 Se Va Prc Va 10 Ala L Phe Ser I Leu S 7 Leu 1 90 His I Thr I Arg Phe Arg 170 Cys Gly Leu Pro Leu 250 Gly Thr Leu Ala Leu 330 1 Leu Gly L Ala o His 1 Thr 410 leu 'al :le ;er '5 la ~eu ?he Ser rhr 155 Gly 3ly 31y Arg Tyr 235 Pro Arg Arg Phe Tyr 315 Prc Gir Tyi Gl Ph 39 Gli Val P Ala A 4 Gly I Thr L Ala L Tyr I Ala I Leu I 140 Phe I Ser I Ala Pro Tyr' 220 Leu Ala Val' Leu Pro 300 Gly Glu 1 Met Leu r Ala 380 Phe 5 ai Ala he G 3 .la F le P ,ys P reu C reu 'ro ~la kla .eu Leu Axrg 205 rhr His Ala Val Leu 285 Val Phe Leu Ile Arg 365 Phe Cys Leu 'ly 0 'he la ,he ly 3er LbO Phr £'hr Pro Leu Leu 190 Ala Val Leu Phe Ser 270 Met Ala Thx Ile Glt Asi Let Phe As Val L Glu G Val G Gly F 8 Met I Ile C Leu 2 Gly Phe I Leu 175 Arg Gin Ala' Val. Leu 255 Gly Leu Gin Ser Gly 335 1 Ser Val a Leu e Ser a Thr 415 r Thr .eu Ilu l1n 'ro 00 ~eu ly Ua eu Phe 160 JTal Pro Leu Leu Ala 240 Leu Trp Trp Ala Gly 320 ThX Ile Ser Ser Thr 400 Lys Glu Val Pro Leu Pro Lys Glu Gly Leu Glu Gly Gly Leu Asn Se: 420 425 43 52/79 Ser Gly Pro Glu Ser Gin Ser Leu Thr Ala Pro Gly Leu Leu Leu Pro 435 440 445 Arg Leu GJ.y Leu His Arg Thr Thr Val Pro CK1450 455 0 <210> 73 IND ~<211>16 C1 <212> PRT <213> homo sapiens <400> 73 IND Met Thr Met Lys Thx Ser Gly Ala Thr Cys Asp Ala Asn Ser Val Met 1 5 10 Asn Cys Gly Ile Aig Gly Ser Glu Met Phe Ala Glu Met Asp lieu Arg 25 Ala Ile Lys Pro Tyr Gin Thr Leu Ile Lys Lys Val Giy Gin Arg His 40 Cys Val Asp Pro Ala Val Ile Ala Ala Ile Ile Ser Arg Giu Ser His 55 Gly Gly Ser Vai Leu Gin Asp Gly Trp, Asp His Arg Gly Leu Lys Phe 70 75 Gly Leu Met Gin Leu Asp Lys Gin Thr TIyr His Pro Val Gly Ala Trp 90 Asp Ser Lys Giu His Leu Ser Gin Ala Thr Gly Ile Leu Thr Giu Arg 100 105 110 Ile Lys Ala Ile Gin Lys Lys Phe Pro Thr Trp, Ser Val Ala Gin His 115 120 125 Leu Lys Gly Gly Leu Ser Ala Phe Lys Ser Gly Ile Giu Ala Ile Ala 130 135 140 Thr Pro Ser Asp Ile Asp Asn Asp Phe Val Asn Asp Ile Ile Ala Arg 145 150 155 160 Ala Lys Phe Tyr Lys Arg Gin Ser Phe 165 <210> 74 <211> 186 <212> PRT <213> homo sapiens <400> 74 Met Lys Pro His Leu His Pro Arg Leu Tyr His Gly Cys Tyr Gly Asp 1 5 10 Ile Met Thr Met Lys Thx Ser Gly Ala Thr Cys Asp Ala Asn Ser Val 25 Met Asn Cys Giy Ile Azg Giy Ser Glu Met Phe Ala Glu Met Asp Leu 40 Arg Ala Ile Lys Pro Tyr Gin Thr Leu Ile Lys Lys Val Gly Gin Arg 55 His Cys Val Asp Pro Ala Val Ile Ala Ala Ile le Ser Axg Glu Ser 70 75 His Gly Giy Ser Val Leu Gin Asp Gly Trp Asp His Arg Gly Leu Lys 90 Phe Gly Leu Met Gin Leu Asp Lys Gin Thr Tyr His Pro Val Gly Ala 100 105 110 Trp Asp Ser Lys Giu His Leu Ser Gin Ala Thr Gly Ile Leu Thx Giu 115 120 125 Arg Ile Lys Ala Ile Gin Lys Lys Phe Pro Thr Trp Ser Val Ala Gin 53/79 130 His Leu Lys 145 Ala Thr Pro Arg Ala Lys 135 140 Gly Gly Leu Ser Ala Phe Lys Ser Gly Ile Giu Ala Ile 150 155 160 Ser Asp Ile Asp Asn Asp Phe Val Asn Asp Ile Ile Ala 165 170 175 Phe Tyr Lys Arg Gin Ser Phe 180 185 <210> <211> 675 <212> PRT <213> homo sapiens <400> Met 1 Asp Val Lys Met Ser Ser Ala Pro Leu 145 Asp Leu Val Leu Ala 225 Ala Ala Gly Asp Ala 305 Phe lu Ala Leu rhr Val Gly Val Trp Glu 130 Ala Met Tyr Ala Ile 210 Val Sex Phe Val Glr 29 Lys IlE Ser Phe Tyr Lys Trp His Ser Ile 115 Tyr Val Tyr Leu Gly 195 Met Gly Asn His Leu 275 Val Gly Met Gly Thr S 5 Pro Gin L Phe Leu P Arg Asp T Trp Pro V 7 Phe Ile G Ala Tyr G 100 Phe Leu P Leu Arg L Leu Tyr L I Ala Gly P 165 Ala Ile 180 Gly Leu 2 Leu Ile C Gly Met C Arg Ser 245 Ile Phe 260 Phe Gly I Ile Val Gly Ala Val Phe er Ser Pro Gin Pro Pro Gin Leu Asp Pro Leu 10 ss he hr Al 0 ly lu 'ro lys ieu .50 la Fal la ;ly 7lu 230 ,Uu k.rg Met ln Leu 310 Pro Gly I Val I Val I 55 Gly I Leu Leu lie Arg 135 Phe Ile Gly Ala Ala 215 Gly Asn Asp Ser Arg 295 Met Gly ~eu ~eu I0 ys kla kla Asn ITyr 120 Phe Ile Phe Leu Val 200 Leu Leu Sex Prc IlE 28C Tin Ale Mel Glu 1 25 Ala Gly Ser I Gly Gly 105 Ile Gly I Tyr Ile Leu 185 Ile Thr Lys Ser Leu 265 Pro Leu i Ala Val Ile 345 ,ro Tal [yr eu Ser 90 Leu Ala Gly Ile Gin 170 Ala Tyr Leu Glu Cys 250 Thr Ser Ala Tyr Ser 330 Cys Gly Gly Phe Phe 75 Gly Phe Gly Ile Phe 155 Gin Ile Thx Met Lys 235 Gly Ser Leu Ala Leu 315 Arg Gir Asp Ile 2 Leu Trp Leu Ala Ala Ser Ala Ala Ser Val Gin Val 125 Arg Ile 140 Thr Lys Ser Leu Thr Ala Asp Ala 205 Gly Tyr 220 Tyr Phe Leu Pro Asp Leu Trp Tyr 285 Lys Asn 300 Lys Val Ile Leu Lys Ile la Ser 31y Asn rhr Leu 110 Thr Pro Ile His Val 190 Leu Ser Leu Arg Pro 270 Trp Leu Leu Phe Cys Val I Thr Gly Val Gly Met Thr Ile Ser Leu 175 Tyr Gin Phe Ala Glu 255 Trp Cys Ser Pro Pro 335 Ser eu 7al ksp 3iy Ile Leu Met Ile Val 160 Asp Thr Thx Ala Leu 240 Asp Pro Thr His. Leu 320 Asp Asn 325 Gln Val Ala Cys Ala Asp Pro G11 340 54,79 Pro Leu Leu 385 Thr Leu Ile Ile Val 465 Phe Leu Pro Ser Pro 545 Asp Leu Val Asp Cys 625 Ala Ser Pro 370 Met Met Met Leu TIyr 450 Phe Trp Asp Val Thr 530 Pro Pro Thr Gin Met 610 Gly Ile Gly 355 Thr Ser Asp Ile Trp 435 Ile Ile Gly Phe Leu 515 Val Ser Val Leu Phe 595 Thr Ile Ile Cys Gly Ser Lieu Vai 420 Ile Gin Met Leu Ile 500 Val Thr Lys Vai Ser 580 Giu Pro Gin Val Ser Leu Leu Trp 405 Gly Pro Ser Gly Ile 485 Tyr Lys Leu Giu Gin 565 Gin Met Lys Glu Ser 645 Asp Arg Thr 390 Asn Arg Vai Ile Cys 470 Ser Val Ser Ile Met 550 Lys Asn Vai Gin Lys 630 Leu Ile Gly. 375 Ser His Val. Val. Ser 455 Phe Giy Gin Ile Thr 535 Vai Giu Gly Gin Ser 615 Giy Glu Ala 360 Leu Ile Leu Phe Gin 440 Ser Trp Leu Pro His 520 Val Ser Gin Met Glu 600 Lys Lys Glu Ty~r Pro Met Met Phe Asn Arg Pro 410 Vai Leu 425 Ala Ser Tyr Leu Lys Arg Leu Leu 490 Arg Cys 505 Tyr Leu Ser Thr His Leu Ala Pro 570 Pro Giu 585 Asn Thr Vai Val Giu Giu Asn Pro 650 Lays Ala Ser 395 Arg Leu Gin Gin Thr 475 Gly Asp Tyr Val Thr 555 Pro Ala Ser Lys Leu 635 Leu Leu Val 380 Ala Ala Leu Gly Pro 460 Asn Leu Gin Phe Ser 540 Trp Ala Ser Lys Ala 620 Pro Val Val 365 Met Ser Ser Val Gly 445 Pro Giu Val Pro Ser 525 Trp Phe Aia Ser Thr 605 Ile Al a Lys Leu Val Thr Giu Leu 430 Gin Val Lys Arg Asp 510 Met Phe Thr Pro Ser 590 His Leu Arg Thr Giu Leu Ala Ala le Phe 400 Lys Giu 415 Vai Ser Leu Phe Ala Val Gly Alai 480 Leu Val 495 Giu Ar g Ile Leu Thr Giu Arg His 560 Leu Ser 575 Ser Ser Ser Cys Trp Leu Ala Glu 640 Leu Leu 655 Asp Vai Asn Leu 660 Tyr Phe Ala 675 Ile Phe Cys Val Ser 665 Cys Ala Ile Phe Ile Trp Gly 670 <210> 76 <211> 485 <212> PRT <213> homo sapiens <400> 76 Met Glu Pro Cys Trp Giy Giu Gly Leu Phe His Leu Ala Pro Pro Arg 1 5 10 His His Pro Gin Lys Ala Asp Trp His Phe Cys Pro Gin His Ile Gin 25 Giu Phe Thr Asn Giu Thr Trp Gin Ala Arg Thr Gly Giu Pro Leu Pro 40 Asp His Leu Val Leu Leu Met Trp Ser Leu Ile Val Ser Leu Tyr Pro 55 Leu Gly Gly Leu Phe Gly Ala Leu Leu Ala Gly Pro Leu Ala Ile Thr 55/79 70 75 Leu Giy Arg Lys Lys Ser Leu Leu Val Asn Asn Ile Phe Val Val Ser 90 Ala Ala Ile Leu Phe Giy Phe Ser Arg Lys Ala Giy Ser Phe Glu Met C) 100 105 110 0 Ile Met Leu Gly Arg Leu Leu Val Giy Val Asn Ala Gly Val Ser Met 115 120 125 Asn Ile Gin Pro Met Tyr Leu Giy Giu Ser Ala Pro Lys Giu Leu Arg 130 135 140 Gly Ala Vai Ala Met Ser Ser Ala Ile Phe Thr Ala Leu Gly Ile Val 145 150 155 160 Met Gly Gin Val Val Gly Leu Arg Giu Leu Leu Giy Gly Pro Gin Ala IND 165 170 175 Trp Pro Leu Leu Leu Ala Ser Cys Leu Val Pro Gly Ala Leu Gin Leu 180 185 190 Ala Ser Leu Pro Leu Leu Pro Glu Ser Pro Arg Tyr Leu Leu Ile Asp tn 195 200 205 Cys Gly Asp Thr Glu Ala Cys Leu Ala Ala Leu Arg Arg Leu Arg Gly 210 215 220 Ser Gly Asp Leu Ala Gly Giu Leu Giu Giu Leu Giu Giu Giu Arg Ala 225 230 235 240 Ala Cys Gin Gly Cys Arg Ala Arg Arg Pro Trp Glu Leu Phe Gin His 245 250 255* Arg Ala Leu Arg Arg Gin Val Thr Ser Leu Val Val Leu Gly Ser Ala 260 265 270 Met Giu Leu Cys Gly Asn Asp Ser Val Tyr Ala Tyr Ala Ser Ser Val 275 280 285 Phe Arg Lys Ala Gly Val Pro Glu Ala Lys Ile Gin Tyr Ala Ile Ile 290 295 300 Gly Thr Gly Ser Cys Glu Leu Leu Thr Ala Val Val Ser Cys Val Val 305 310 315 320 Ile Giu Arg Val Gly Arg Arg Val Leu Leu Ile Gly Gly Tyr Ser Leu 325 330 335 Met Thr Cys Trp Gly Ser Ile Phe Thr Val Ala Leu Cys Leu Gin Ser 340 345 350 Ser Phe Pro Trp Thr Leu Tyr Leu Ala Met Ala Cys Ile Phe Ala Phe 355 360 365 Ile Leu Ser Phe Gly Ile Gly Pro Ala Gly Val Thr Gly Ile Leu Ala 370 375 380 Thr Giu Leu Phe Asp Gin Met Ala Arg Pro Ala Ala Cys Met Val Cys 385 390 395 400 Gly Ala Leu Met Trp Ile Met Leu Ile Leu Val Gly Leu Gly Phe Pro 405 410 415 Phe Ile Met Glu Ala Leu Ser His Phe Leu Tyr Val Pro Phe Leu Gly 420 425 430 Val Cys Val Cys Gly Ala Ile Tyr Thr Gly Leu Phe Leu Pro Glu Thr 435 440 445 Lys Gly Lys Thr Phe Gin Giu Ile Ser Lys Glu Leu His Arg Leu Asn 450 455 460 Phe Pro Arg Arg Ala Gin Gly-Pro Thr Trp Arg Ser Leu Glu Val Ile 465 470 475 480 Gin Ser Thr Giu Leu 485 <210> 77 <211> 496 <212> PRT <213> homo sapiens 56/79 <400> 77 Met Arg Ala Len Arg Arg Leu Ile Gin Giy Arg Ile Leu Len Leu Thr Ile C Ser I Thr '9 Leu 1 Gly 2 Ser I Gly I Leu I Tyr 145 Ser Gly Ala Leu Ala 225 Gly Arg Gin Asn Val 305 Glu Arg Ser Len Ile 385 Gin Ile Leu .ys :le Prp det kla eu The eu 130 Leu Ser Leu Ser Pro 210 Cys Glu Ala Vai Asp 290 Pro Leu Arg Ile Tyr 37 G1 Met Mel Se Ala Ile Gin Trp Leu Leu Ser 115 Val Gly Ala Arg Cys 195 Glu Leu Leu Arg Thr 275 Ser Gli Lei Val PhE 351 Let r Prc *Al~ Lei Hi 43! Ala C Asn I Ala 2 Ser I Leu 2 Val .2 100 Arg I Gly Glu Ile Glu 180 Leu Ser Ala Glu Arg 260 Ser Val Ala Thr Leu 340 Thr i Ala Ala a Arg u Ile 420 s Phe 5 ly ~la Lrg eu la lsn Lys lal Ser Phe 165 Leu Val Pro Ala Glu 245 Pro Leu Tyr Lys Ala 325 Leu Val Met Gly Pro 405 Let Let Ile C Pro 9I ThX C Ile 1 70 Gly I Asn Ala Asn Ala 150 Thr Leu Pro Arg Leu 230 Leu Trp Val Ala Ile 310 Val Ile Ala Ala Val 390 Ala Val STyr ly 'hr ;ly 5 lal ?ro Ile ly kla 135 Pro Ala Gly Gly Tyr 215 Arg Glu Glu Val Tyr 295 Gin Val Gly Leu CyE 375 Tin Ala Gi) Val Gly Leu 40 Glu Ser Len Phe Ser 120 Gly Lys Leu Gly Ala 200 Leu Arg Glu Len Leu 280 Ala Tyr Ser Glj ys 36C 1i( Gl) LCy~ r Let L Pr 44 Thr P 25 His I Pro L Len Ala I Val 1 105 Phe Val Glu I Gly Pro 185 Len C Len Leu Glu. Phe 265 Gly Ser Ala Cys STyr 345 Len Phe SIle 3 Met a Gly 425 o Phe 0 he le reu -Yr :le 00 Ta! ;lu Ser eu Ile 170 3ml Gln Ile Arg 250 Gin Ser Ser Ile Val 330 Ser Gin Ala Let Val 41C Phe Let Gin P Gin G Pro A 6 Pro L 75 Thr L Ser P Met I Met Arg C 155 Val a Ala Leu 2 Asp Gly 235 Ala His Ala Val Ile 315 Val Leu Ser Phe Ala 395 Cys Pro a Gly he lu ~sp eu reu la :le ~sn ;ly det rrp kla Cys 220 Ser Ala Arg Met Phe 300 Gly Ile Met Sex IlE 380 Thz G11 Phe Va. Gly Phe His Gly Gly Ala Met 125 Ile Ala Gly Pro Ser 205 Gly Gly Cys Ala Glu 285 Arg Thi Glu T]n Phf 361 Let *G1~ r Ai t Ilt L Cy: 44 Tyr A Thr P Leu I Gly I Arg I Ile I 110 Len Gin I Val 2 Gin I Len 190 Len Asp Asp Gin Len 270 Leu Lys Gly Arg Cys 350 Pro a Ser a Leu Len Met 430 s Val Isn sn tal leu rys jeu 'ly ?ro Ua lal 175 Len Pro lhr Len Gly 255 Arg Cys Ala Ser Val 335 Trr Trr PhE Phe Met 41 GlI CYu Len Glu Leu Phe Lys Phe Arg Met Met 160 Val Len Len Glu Ala 240 Cys Arg Gly Gly Cys 320 Gly Gly )Thr Gly Asp 400 Trp a Ala s Gly Ala Ile Tyr Thr Gly Len Phe Len Pro Glu Thr Lys Gly Lys Thr Phe 57/79 450 455 460 Gin Giu Ile Ser Lys Glu Leu His Arg Leu Asn Phe Pro Arg Arg Ala 465 470 475 480 Gin Gly Pro Thr Trp Arg Ser Leu Giu Val Ile Gin Ser Thr Giu Leu 485 490 495 <210> 78 <211> 500 <212> PRT <213> homo sapiens <400> 78 Asx Met Leu His Ala Leu Leu Arg Ser Arg Met Ile Gin Gly Arg Ile 1 Leu Gly Phe His Gly Gly Ala Met Ile 145 Ala Gly Pro Ser Gly 225 Gly Cys Ala Glu Arg 305 Thr Glu Leu ryr rhr Leu Gly Arg Ile Leu 130 Gin Val Gin Leu Leu 210 Asp Asp Gin Leu Leu 290 Lys GlN ArG Leu Asn Asn Vai Leu Lys Leu 115 Gly Pro Ala Vai Leu 195 Pro Thr Leu Gly Arg 275 *Cys Ala Sex Val 5 10 Thr Leu Glu Leu Phe Lys 100 Phe Arg Met Met Vai 180 Leu Leu Glu Ala Cys 260 Arg Gly Gly Cys Gly 340 Ile Ser rhr Leu Gly Ser Gly Leu Tyr Ser 165 Gly Ala Leu Ala Gly 245 Arg Gin Asn Val Gl- 32S Ar Cys 2 lie Trp Met 70 Ala Leu Phe Leu Leu 150 Ser Leu Ser Pro Cys 230 Glu Ala Val Asp Pro 310 Leu Arg kia Ile ,ln 35 rrp Leu Leu Ser Val 135 Gly Ala Arg Cys Glu 215 Leu Leu Arg Thr Ser 295 Glu Leu Val Ala Asn 40 Ala Ser Leu Vai Arg 120 Gly Glu Ile Glu Leu 200 Ser Ala Glu Arg Ser 280 Val Ala Thi Lei Gly Ala Arg Leu Ala 4 Asn 105 Lys Val Ser Phe Leu 185 Val Pro Ala Glu Pro 265 Leu Tyr Lys Ala Leu 345 Ile Pro rhr lie Gly 90 Asn Ala Asn Ala Thr 170 Leu Pro Arg Leu Leu 250 Trp Val Ala Ile Val 330 Ile Gly C Thr I Gly C Val 75 Pro I Ile Gly Ala Pro 155 Ala Gly 4 Gly. Tyr Arg 235 Glu Glu Val Tyr Gin 315 Val Gly ;ly ieu lu 00 3er eu Phe Ser ly 140 Lys Leu ly Ala Leu 220 Arg Glu Leu Leu Ala 300 Tyr Sex G13 Thr His Pro Leu Ala Val Phe 125 Val Glu Gly Pro Leu 205 Leu Leu Glu Phe Gly 285 Ser Ala Cys STyr ?he Cle eu Pyr Ile V.al 110 3iu Ser Leu Ile Gin 190 Gin Ile Arg Arg Gin 270 Ser Ser Ile Val Sex 350 Gin I Gin Pro 2 Pro Thr Ser Met Met Arg Val 175 Ala Leu Asp Gly Ala 255 His Ala Val Ile Val 335 Leu ?he 31u %sp Leu Leu Ala Ile Asn Gly 160 Met Trp Ala Cys Ser 240 Ala Axg Met Phe Gly 320 Ile Met Thr Cys Trp Giy Ser Ile Phe Thr Vai Ala Leu Cys Leu Gin Ser Ser 355 360 365 58/79 Phe Leu 385 Glu Ala Ile Cys Gly 465 Pro Ser Trp Thx Phe Gly Phe Asp Met Trp 420 Glu Ala 435 Cys Gly Thr Phe Arg Ala Glu Len 500 Leu Ile Gin 405 Ile Len Ala Gin Gin 485 Tyr Gly 390 Met Met Ser Ile Glu 470 Gly Leu 375 Pro Ala Len His Tyr 455 Ile Pro Ala Ala Arg Ile Phe 440 Thr Ser Thr Met Gly Pro Leu 425 Len Gly Lys Trp Ala Val Ala 410 Val Tyr Leu Glu Arg 490 Cys Thr 395 Ala Giy Val Phe Len 475 Ser Ile 380 Gly Cys Leu Pro Leu 460 His Len Phe Ile Met Gly Phe 445 Pro Arg Glu Phe Ala Cys 415 Pro Gly Thr Asn Ile 495 Ile Thr 400 Gly Phe Val Lys Phe 480 Gin <210> 79 <211> 1358 <212> PRT <213> homo sapiens <400> 79 Met Val 1 Asn Thr Pro Ala Leu Glu Len Val Thz Val Arg Asp Gly Gly Val Asp 130 Ala Glu 145 Asp Met Phe Leu Glu Lys Tyr Glu 210 Arg Leu 225 Asp Gin Val 3iy Gly Ala Ile Ala Gly Arg 115 Asp Gly Asp Thr Gin 195 Arg Phe Phe Val Len Ser Val Leu Glu Ser 100 His Gin Glu Ser Thr 180 Glu Thr Tyr Thr Lys 5 Ile Gly Arg Gly Leu Len Gin Pro Thr Asp 165 Gly Leu Val Arg Phe Pro Met Asn Thr Met Ala Pro Val Val Thr Arg Len Pro Leu Ala 70 Ala Ser Val Pro Vai 150 Asp His Len Thr His 230 Arg Tyr Gin Glu 55 Ser Ala Asp Gin Val 135 Pro Ser Len Arg Glu 215 Ser Val Glu Asn 40 Val Ser Gly Asn Phe 120 Len Ile Leu Len Gly 200 Trp Gly Gin Gly I 25 Len Val Gly Gin Len 105 Len Asn Len Len Len 185 Len Gin Pro Asp 10 3Gl V1al Ala Ser Val 90 Val Phe Ala Pro Len 170 Arg Trp Gin His Asn 250 Ser Ile Gly Ser 75 Val Leu Pro Asn Len 155 Phe Gin Arg Gin Ser 235 His Arg Ser Leu Ala Tyr Arg Ile Thr 140 Ser Val Thr Lys Asp 220 Pro Asp Pro Asp Arg Pro Gin Met Thr 125 Gly Len Len His Glu 205 Ile Gly Pro Len Glu His Lys His Vai 110 Len Len Ser Glu Pro 190 Gly Thr Pro Pro Thr Asp Gly Ser Asp Asp Val Thr Ala Ser 175 Pro Ala Glu Vai Asn Gly Asp His Phe Asp Gly Pro Leu Thz 160 Pro His Phe Gly Thr 240 Gin 245 255 Ser Gly Len Gin Arg Phe Val Ile Arg Ile His Pro Val Asp Arg Len 5979 260 265 Pro Ser Asp 305 Asp Thr Asn Ala Asn 385 Gin His Asp His Leu 465 Lys Val Val Val Thx 545 Pro Phe Ser Let Glj 62 GitL Va AsE Glr Al Pro Giu Leu 275 Gin Leu Thr 290 Thr Asp Asp Thr Asp Glu Asp Asn Pro 340 His His Lys 355 Thr Arg Val 370 Val Ala Pro Pro Pro Glu His Ile Leu 420 Val Ala His 435 Met Arg Val 450 Glu Asp Ile Ser Leu ThI Val Pro le Pro Ile Let 515 Leu Giu As 530 Asn Giu GI Pro Leu Ty- Thr Gin Ar. 58 Gly Giu 11 595 Ser Asp Me 610 r Val Thr I Ile Phe Va L Ile Thr Se 66 Asp Ile Le 675 u Asn Ile Se 690 a Ile Ser Al 5 I n r 1 1 r E E t t Gly Ser G: Pro Leu A 2 Arg Glu L 310 Asn His L 325 Ser Vai V Ile Ala T Ala Gin P 3 Gly Thr P 390 Ile Leu A 405 Ser Giu T Ile Ser P Ser Gly C 4 Lys Gln C 470 Asp Ser C 485 Thr Leu I Ser His I Gly Ala Thr Asp 550 Giy Glu 565 1 Asp Ile Giy Leu t Ser Gin a Trp Val 630 1 Gly Glu 645 r Val His 0 u Cys Thr r Pro Ala a Phe Asn 710 ly 95 eu eu al yr he 75 he sn hr ,he lIn 155 iy ~ys ?ro hr 535 Asp Ile Leu Leu Glu 615 Thx Gir le Ile Prc 69! Lei Cys 280 Lys Arg Pro Val Arg 360 Gin Thr Thr Glu Thr 440 Ile Arg Ser Vai Thr 520 Glu Leu Leu SGlL, Pro 600 Trn le 1 Let 5 Se~ a Va 68 o Gi: ,Ly P Lys Tyr Ala Thr 345 Pro Phe Leu Gly Leu 425 Leu Leu Vai Leu Asn 505 Gly Ile Met Val GI1 58! Ly Are 3 Le 1 114 c Al 66 L I]. y Se s As Trp L Thr V 3 Pro L 330 His P Pro G Gin V Tyr L 3 Phe I 410 His Thr C His Ser Glu 490 Vai Thn Thr Leu Asn 570 r Ser 3 Ala g~ Ile u Pro a Val 650 a Glu 5 e Gin r Glu p Leu eu al 15 eu he ly 'al leu 95 'hr ral ln Tai [yr 175 Tal krg Eeu Ala Thr 555 GlN Val Asl Gi Va 63! Me As Pr Ly Ar 71 Arg Tyr T 300 Thr Gln S Gly Thr L Thr Gin A 3 Gin Giu L 365 Glu Asp A 380 His Pro T Ile Gin G Asn Asp X Ala Pro I 445 Gly Giy I 460 Ala His I Sen Asp Pro Vai Giu Ser 525 Asn Vai 540 Phe Leu Ile Pro Val Tyr Ser Phe 605 I Gly Asn 620 L Asp Ser t Giu Gly p Val Asp o Thr Ser 685 s Ser Arg 700 g Gin Gly 5 hr er eu la eu xg 'al ;lu rai ~eu ksn I~rg ksp 510 Tyr Ile Leu Ala Thi 590 Asr Th3 Gl AsI Se: 67 Gi1 Al Hi Asp L Pro T 3 Val L 335 Gin I Gly V Ala G Asp A 4 Lys G 415 Asp T His G Phe I Gly I His I 495 Asp Leu Lys Glu Glu 575 His i Leu Ile i Ala p Lys 655 r Leu 0 e Tyr a Gly s Ile eu hr eu le al ly sn :00 Ily Ihr ;ly Iis ~sp fis ;lu ssp ly Asp 560 Gln Thr Ser Gin Pro 640 Ser As Val Ile As 720 ro Leu Arg Met Val Val Gin Glu 285 Tyr Val Gin Ser Val 725 His Lys Gly Val Glu 730 6079 Pro Vai Giu Asp Arg Phe 735 Val Phe Arg Cys Ser Asp Gly Ile Asn Phe Ser Glu Arg Gin Phe Phe 0 740 745 750 Pro Ile Val lie Ile Pro Thr Asn Asp Glu Gin Pro Glu Met Phe Met N 755 760 765 Arg Glu Phe Met Val Met Glu Gly Met Ser Leu Val Ile Asp Thr Pro 770 775 780 Ile Leu Asn Ala Ala Asp Ala Asp Val Pro Leu Asp Asp Leu Thr Phe IN 785 790 795 800 C Thr Ile Thr Gin Phe Pro Thr His Gly His Ile Met Asn Gin Leu Ile 805 810 815 Asn Gly Thr Val Leu Val Glu Ser Phe Thr Leu Asp Gin Ile Ile Glu n 820 825 830 ND Ser Ser Ser Ile Ile Tyr Glu His Asp Asp Ser Glu Thr Gln Glu Asp 835 840 845 Ser Phe Val Ile Lys Leu Thr Asp Gly Lys His Ser Val Glu Lys Thr 850 855 860 V Val Leu Ile Ile Val Ile Pro Val Asp Asp Glu Thr Pro Arg Met Thr S865 870 875 880 Slie Asn Asn Gly Leu Glu Ile Glu Ile Gly Asp Thr Lys Ile Ile Asn N 885 890 895 Asn Lys Ile Leu Met Ala Thr Asp Leu Asp Ser Glu Asp Lys Ser Leu 900 905 910 Val Tyr Ile Ile Arg Tyr Gly Pro Gly His Gly Leu Leu Gin Arg Arg 915 920 925 Lys Pro Thr Gly Ala Phe Glu Asn Ile Thr Leu Gly Met Asn Phe Thr 930 935 940 Gin Asp Glu Val Asp Arg Asn Leu Ile Gin Tyr Val His Leu Gly Gin 945 950 955 960 Glu Gly Ile Arg Asp Leu Ile Lys Phe Asp Val Thr Asp Gly Ile Asn 965 970 975 Pro Leu Ile Asp Arg Tyr Phe Tyr Val Ser I3e Gly Ser Ile Asp Ile 980 985 990 Val Phe Pro Asp Val Ile Ser Lys Gly Val Set Leu Lys Glu Gly Gly 995 1000 1005 Lys Val Thr Leu Thr Thr Asp Leu Leu Ser Thr Ser Asp Leu Asn Ser 1010 1015 1020 Pro Asp Glu Asn Leu Val Phe Thr Ile Thr Arg Ala Pro Met Arg Gly 1025 1030 1035 1040 His Leu Glu Cys Thr Asp Gin Pro Gly Val Ser Ile Thr Ser Phe Thr 1045 1050 1055 Gin Leu Gin Leu Ala Gly Asn Lys Ile Tyr Tyr Ile His Thr Ala Asp 1060 1065 1070 Asp Glu Val Lys Met Asp Ser Phe Glu Phe Gin Val Thr Asp Gly Arg 1075 1080 1085 Asn Pro Val Phe Arg Thr Phe Arg Ile Ser Ile Ser Asp Val Asp Asn 1090 1095 1100 Lys Lys Pro Val Val Thr Ile His Lys Leu Val Val Ser Glu Ser Glu 1105 1110 1115 1120 Asn Lys Leu Ile Thr Pro Phe Glu Leu Thr Val Glu Asp Arg Asp Thr 1125 1130 1135 Pro Asp Lys Leu Leu Lys Phe Thr Ile Thr Gin Val Pro Ile His Gly 1140 1145 1150 His Leu Leu Phe Asn Asn Thr Arg Pro Val Met Val Phe Thr Lys Gin 1155 1160 1165 Asp Leu Asn Glu Asn Leu Ile Ser Tyr Lys His Asp Gly Thr Glu Ser 1170 1175 1180 Ser Glu Asp Ser Phe Ser Phe Thr Val Thr Asp Gly Thr His Thr Asp 1185 1190 1195 1200 Phe Tyr Val Phe Pro Asp Thr Val Phe Glu Thr Arg Arg Pro Gin Val 61/79 Met Val Gly Len 1265 Tyr Gin Ala Lys Gly 1345 1205 1210 1215 Lys Ile Gin Val Leu Ala Val Asp Asn Ser Val Pro Gin Ile Ala 1220 1225 1230 Asn Lys Gly Ala Ser Thr Leu Arg Thr Leu Ala Thr Gly His Leu 1235 1240 1245 Phe Met Ile Thr Ser Lys Ile Len Lys Val Gin Asp Arg Asp Ser 1250 1255 1260 His Ile Ser Leu Arg Phe Ile Val Thx Glu Ala Pro Gin His Gly 1270 1275 1280 Leu Leu Asn Leu Asp Lys Gly Asn His Ser Ile Thr Gin Phe Thr 1285 1290 1295 Ala Asp Ile Asp Asp Met Lys Ile Cys Tyr Val Leu Arg Glu Gly 1300 1305 1310 Asn Ala Thr Ser Asp Met Phe Tyr Phe Ala Val Glu Asp Gly Gly 1315 1320 1325 Tyr Ser Pro Leu Len Val Val Thr Ala Arg Arg Asp Ala Phe Len 1330 1335 1340 Cys Ser Leu Met Thr Leu Len Gin Glu Val Phe Ile Lys 1350 1355 <210> <211> 3105 <212> PRT <213> homo sapiens <400> Met Ala Arg Ser Trp Leu Thr Ala Thr Ser Thr Ser Arg Pro Ala Ala I Phe I Pro Phe Val Leu Phe Ser Ala Len 145 Gly Pro Leu Ala 10 G1y Ala Gly Gin Ala Gly Arg Val 130 Glu Thr Glu Pro Arg Arg Glu Arg Pro Gin Pro Asp 115 Val Val Ser Thr Arg 195 Glu Ala Glu Glu Gly Arg Gly 100 Arg Leu Val Asn Glu 180 Tyr Gly Leu Ala Val Asp Pro Glu Val Pro Thr Ala 165 Glu Gly Gly Leu Ile Trp Arg 70 Gly Val Arg Len Arg 150 Leu Cys Glu Ala Val 230 Ser Val Leu 55 Cys Arg Arg Len Val 135 Asn Asp Arg Len Pro 215 Ar Pro Leu 40 Asp Ala Leu Tyr Gin 120 Len Len Ala Val Leu 200 Glu Tyr lyI 25 Ala Pro Val Ser Ser 105 Len Glu Pro Arg Gly 185 His Thr Arg jeu ksn Leu Ser Pro 90 His Arg Val Leu Ser 170 Ile Tyr Len His Ala Arg His Val 75 Lys Leu Tyr Glu Val 155 Leu Leu Pro Leu Thr 235 Glu 31y 21y Asp Leu Arg Gly Asp Val 140 Val Glu Ser Gin Met 220 Ala Len Ala Leu Len Asp Phe Ala Ala 125 Val Glu Phe Gly Val 205 Asp Ala Arg kla k.rg Val Asn Pro Arg 110 Pro Phe Glu Ala Len 190 Pro Cys Ser Ser Gly Val Len Asp Cys Ser Gly Thr Leu Phe 175 Gly Gly Lys Arg Arg 255 7al Pro ln Ala Asp Pro Gly Gin Leu 160 Gin Ala Gly Ala Ser 240 Gly 210 Phe Gin Glu Len Gly 225 Pro Asn Arg Asp Trp Ile Pro Met Val Val 250 62/79 n) Ala Pro Val Gly Ser Pro Ala Leu Lys Arg Glu His Phe Gin Val Leu 260 265 270 O Val Arg Ile Arg Gly Gly Ala Glu Asn Thr Ala Pro Lys Pro Ser Phe C 275 280 285 Val Ala Met Met Met Met Glu Val Asp Gin Phe Val Leu Thr Ala Leu 290 295 300 Thr Pro Asp Met Leu Ala Ala Glu Asp Ala Glu Ser Pro Ser Asp Leu IN 305 310 315 320 SLeu Ile Phe Asn Leu Thr Ser Pro Phe Gin Pro Gly Gin Gly Tyr Leu 325 330 335 Val Ser Thr Asp Asp Arg Ser Leu Pro Leu Ser Ser Phe Thr Gin Arg 340 345 350 u Asp Leu Arg Leu Leu Lys Ile Ala Tyr Gin Pro Pro Ser Glu Asp Ser 355 360 365 Asp Gin Glu Arg Leu Phe Glu Leu Glu Leu Glu Val Val Asp Leu Glu C 370 375 380 n Gly Ala Ala Ser Asp Pro Phe Ala Phe Met Val Val Val Lys Pro Met 385 390 395 400 Asn Thr Met Ala Pro Val Val Thr Arg Asn Thr Gly Leu Ile Leu Tyr 405 410 415 Glu Gly Gin Ser Arg Pro Leu Thr Gly Pro Ala Gly Ser Gly Pro Gin 420 425 430 Asn Leu Val Ile Ser Asp Glu Asp Asp Leu Glu Ala Val Arg Leu Glu 435 440 445 Val Val Ala Gly Leu Arg His Gly His Leu Val Ile Leu Gly Ala Ser 450 455 460 Ser Gly Ser Ser Ala Pro Lys Ser Phe Thr Val Ala Glu Leu Ala Ala 465 470 475 480 Gly Gin Val Val Tyr Gin His Asp Asp Arg Asp Gly Ser Leu Ser Asp 485 490 495 Asn Leu Val Leu Arg Met Val Asp Gly Gly Gly Arg His Gin Val Gin 500 505 510 Phe Leu Phe Pro Ile Thr Leu Val Pro Val Asp Asp Gin Pro Pro Val 515 520 525 Leu Asn Ala Asn Thr Gly Leu Thr Leu Ala Glu Gly Glu Thr Val Pro 530 535 540 Ile Leu Pro Leu Ser Leu Ser Ala Thr Asp Met Asp Ser Asp Asp Ser 545 550 555 560 Leu Leu Leu Phe Val Leu Glu Ser Pro Phe Leu Thr Thr Gly His Leu 565 570 575 Leu Leu Arg Gin Thr His Pro Pro His Glu Lys Gin Glu Leu Leu Arg 580 585 590 Gly Leu Trp Arg Lys Glu Gly Ala Phe Tyr Glu Arg Thr Val Thr Glu 595 600 605 Trp Gin Gin Gin Asp Ile Thr Glu Gly Arg Leu Phe Tyr Arg His Ser 610 615 620 Gly Pro His Ser Pro Gly Pro Val Thr Asp Gin Phe Thr Phe Arg Val 625 630 635 640 Gin Asp Asn His Asp Pro Pro Asn Gin Ser Gly Leu Gin Arg Phe Val 645 650 655 Ile Arg Ile His Pro Val Asp Arg Leu Pro Pro Glu Leu Gly Ser Gly 660 665 670 Cys Pro Leu Arg Met Val Val Gin Glu Ser Gin Leu Thr Pro Leu Arg 675 680 685 Lys Lys Trp Leu Arg Tyr Thr Asp Leu Asp Thr Asp Asp Arg Glu Leu 690 695 700 Arg Tyr Thr Val Thr Gin Pro Pro Thr Asp Thr Asp Glu Asn His Leu 705 710 715 720 Pro Ala Pro Leu Gly Thr Leu Val Leu Thr Asp Asn Pro Ser Val Val 63/79 In 725 730 735 0 Val Thr His Phe Thr Gin Ala Gin Ile Asn His His Lys Ile Ala Tyr 740 745 750 Arg Pro Pro Gly Gin Glu Leu Gly Val Ala Thr Arg Val Ala Gin Phe o 755 760 765 O Gin Phe Gin Val Glu Asp Arg Ala Gly Asn Val Ala Pro Gly Thr Phe 770 775 780 IN Thr Leu Tyr Leu His Pro Val Asp Asn Gin Pro Pro Glu Ile Leu Asn l 785 790 795 800 Thr Gly Phe Thr Ile Gin Glu Lys Gly His His Ile Leu Ser Glu Thr 805 810 815 n Glu Leu His Val Asn Asp Val Asp Thr Asp Val Ala His Ile Ser Phe ND 820 825 830 Thr Leu Thr Gin Ala Pro Lys His Gly His Met Arg Val Ser Gly Gin C-K 835 840 845 C Ile Leu His Val Gly Gly Leu Phe His Leu Glu Asp Ile Lys Gin Gly n 850 855 860 SArg Val Ser Tyr Ala His Asn Gly Asp Lys Ser Leu Thr Asp Ser Cys 865 870 875 880 Ser Leu Glu Val Ser Asp Arg His His Val Val Pro Ile Thr Leu Arg 885 890 895 Val Asn Val Arg Pro Val Asp Asp Glu Val Pro Ile Leu Ser His Pro 900 905 910 Thr Gly Thr Leu Glu Ser Tyr Leu Asp Val Leu Glu Asn Gly Ala Thr 915 920 925 Glu Ile Thr Ala Asn Val Ile Lys Gly Thr Asn Glu Glu Thr Asp Asp 930 935 940 Leu Met Leu Thr Phe Leu Leu Glu Asp Pro Pro Leu Tyr Gly Glu Ile 945 950 955 960 Leu Val Asn Gly Ile Pro Ala Glu Gin Phe Thr Gin Arg Asp Ile Leu 965 970 975 Glu Gly Ser Val Val Tyr Thr His Thr Ser Gly Glu Ile Gly Leu Leu 980 985 990 Pro Lys Ala Asp Ser Phe Asn Leu Ser Leu Ser Asp Lys Ser Gin Glu 995 1000 1005 Trp Arg Ile Gly Gly Asn Thr Ile Gin Gly Val Thr Ile Trp Val Thr 1010 1015 1020 Ile Leu Pro Val Asp Ser Gin Ala Pro Glu Ile Ser Val Gly Glu Gin 1025 1030 1035 1040 Leu Ile Val Met Glu Gly Asp Lys Ser Val Ile Thr Ser Val His Ile 1045 1050 1055 Ser Ala Glu Asp Val Asp Ser Leu Asn Asp Asp Ile Leu Cys Thr Ile 1060 1065 1070 Val Ile Gin Pro Thr Ser Gly Tyr Val Glu Asn Ile Ser Pro Ala Pro 1075 1080 1085 Gly Ser Glu Lys Ser Arg Ala Gly Ile Ala Ile Ser Ala Phe Asn Leu 1090 1095 1100 Lys Asp Leu Arg Gin Gly His Ile Asn Tyr Val Gin Ser Val His Lys 1105 1110 1115 1120 Gly Val Glu Pro Val Glu Asp Arg Phe Val Phe Arg Cys Ser Asp Gly 1125 1130 1135 Ile Asn Phe Ser Glu Arg Gin Phe Phe Pro Ile Val Ile Ile Pro Thr 1140 1145 1150 Asn Asp Glu Gin Pro Glu Met Phe Met Arg Glu Phe Met Val Met Glu 1155 1160 1165 Gly Met Ser Leu Val Ile Asp Thr Pro Ile Leu Asn Ala Ala Asp Ala 1170 1175 1180 Asp Val Pro Leu Asp Asp Leu Thr Phe Thr Ile Thr Gin Phe Pro Thr 1185 1190 1195 1200 64/79 9 His Gly His lle Met Asn Gin Leu Ile Asn Gly Thr Val Leu Val Glu 1205 1210 1215 Ser Phe Thr Leu Asp Gin Ile Ile Glu Ser Ser Ser Ile Ile Tyr Glu 1220 1225 1230 o His Asp Asp Ser Glu Thr Gin Glu Asp Ser Phe Val Ile Lys Leu Thr 0 1235 1240 1245 Asp Gly Lys His Ser Val Glu Lys Thr Val Leu Ile Ile Val Ile Pro IO 1250 1255 1260 Val Asp Asp Glu Thr Pro Arg Met Thr Ile Asn Asn Gly Leu Glu Ile 1265 1270 1275 1280 Glu Ile Gly Asp Thr Lys Ile Ile Asn Asn Lys Ile Leu Met Ala Thr 1285 1290 1295 \O Asp Leu Asp Ser Glu Asp Lys Ser Leu Val Tyr Ile Ile Arg Tyr Gly 1300 1305 1310 c- Pro Gly His Gly Leu Leu.Gln Arg Arg Lys Pro Thr Gly Ala Phe Glu C1 1315 1320 1325 Q Asn Ile Thr Leu Gly Met Asn Phe Thr Gin Asp Glu Val Asp Arg Asn 1330 1335 1340 Leu Ile Gin Tyr Val His Leu Gly Gin Glu Gly Ile Arg Asp Leu Ile 1345 1350 1355 1360 Lys Phe Asp Val Thr Asp Gly Ile Asn Pro Leu Ile Asp Arg Tyr Phe 1365 1370 1375 Tyr Val Ser Ile Gly Ser Ile Asp Ile Val Phe Pro Asp Val Ile Ser 1380 1385 1390 Lys Gly Val Ser Leu Lys Glu Gly Gly Lys Val Thr Leu Thr Thr Asp 1395 1400 1405 Leu Leu Ser Thr Ser Asp Leu Asn Ser Pro Asp Glu Asn Leu Val Phe 1410 1415 1420 Thr Ile Thr Arg Ala Pro Met Arg Gly His Leu Glu Cys Thr Asp Gin 1425 1430 1435 1440 Pro Gly Val Ser Ile Thr Ser Phe Thr Gin Leu Gin Leu Ala Gly Asn 1445 1450 1455 Lys Ile Tyr Tyr Ile His Thr Ala Asp Asp Glu Val Lys Met Asp Ser 1460 1465 1470 Phe Glu Phe Gin Val Thr Asp Gly Arg Asn Pro Val Phe Arg Thr Phe 1475 1480 1485 Arg Ile Ser Ile Ser Asp Val Asp Asn Lys Lys Pro Val Val Thr Ile 1490 1495 1500 His Lys Leu Val Val Ser Glu Ser Glu Asn Lys Leu Ile Thr Pro Phe 1505 1510 1515 1520 Glu Leu Thr Val Glu Asp Arg Asp Thr Pro Asp Lys Leu Leu Lys Phe 1525 1530 1535 Thr Ile Thr Gin Val Pro Ile His Gly His Leu Leu Phe Asn Asn Thr 1540 1545 1550 Arg Pro Val Met Val Phe Thr Lys Gin Asp Leu Asn Glu Asn Leu Ile 1555 1560 1565 Ser Tyr Lys His Asp Gly Thr Glu Ser Ser Glu Asp Ser Phe Ser Phe 1570 1575 1580 Thr Val Thr Asp Gly Thr His Thr Asp Phe Tyr Val Phe Pro Asp Thr 1585 1590 1595 1600 Val Phe Glu Thr Arg Arg Pro Gin Val Met Lys Ile Gin Val Leu Ala 1605 1610 1615 Val Asp Asn Ser Val Pro Gin Ile Ala Val Asn Lys Gly Ala Ser Thr 1620 1625 1630 Leu Arg Thr Leu Ala Thr Gly His Leu Gly Phe Met Ile Thr Ser Lys 1635 1640 1645 Ile Leu Lys Val Glu Asp Arg Asp Ser Leu His Ile Ser Leu Arg Phe 1650 1655 1660 Ile Val Thr Glu Ala Pro Gin His Gly Tyr Leu Leu Asn Leu Asp Lys 65/79 1665 1670 1675 1680 SGly Asn His Ser Ile Thr Gin Phe Thr Gin Ala Asp Ile Asp Asp Met 1685 1690 1695 Lys Ile Cys Tyr Val Leu Arg Glu Gly Ala Asn Ala Thr Ser Asp Met 0 1700 1705 1710 O Phe Tyr Phe Ala Val Glu Asp Gly Gly Gly Asn Lys Leu Thr Tyr Gin 1715 1720 1725 -O Asn Phe Arg Leu Asn Trp Ala Trp Ile Ser Phe Glu Lys Glu Tyr Tyr 1730 1735 1740 Leu Val Asn Glu Asp Ser Lys Phe Leu Asp Val Val Leu Lys Arg Arg 1745 1750 1755 1760 IN Gly Tyr Leu Gly Glu Thr Ser Phe Ile Ser Ile Gly Thr Arg Asp Arg S1765 1770 1775 Thr Ala Glu Lys Asp Lys Asp Phe Lys Gly Lys Ala Gin Lys Gin Val 1 1780 1785 1790 CGin Phe Asn Pro Gly Gin Thr Arg Ala Thr Trp Arg Val Arg Ile Leu 1795 1800 1805 SSer Asp Gly Glu His Glu Gin Ser Glu Thr Phe Gin Val Val Leu Ser 1810 1815 1820 Glu Pro Val Leu Ala Ala Leu Glu Phe Pro Thr Val Ala Thr Val Glu 1825 1830 1835 1840 Ile Val Asp Pro Gly Asp Glu Pro Thr Val Phe Ile Pro Gin Ser Lys 1845 1850 1855 Tyr Ser Val Glu Glu Asp Val Gly Glu Leu Phe Ile Pro Ile Arg Arg 1860 1865 1870 Ser Gly Asp Val Ser Gin Glu Leu Met Val Val Cys Tyr Thr Gin Gin 1875 1880 1885 Gly Thr Ala Thr Gly Thr Val Pro Thr Ser Val Leu Ser Tyr Ser Asp 1890 1895 1900 Tyr Ile Ser Arg Pro Glu Asp His Thr Ser Val Val Arg Phe Asp Lys 1905 1910 1915 1920 Asp Glu Arg Glu Lys Leu Cys Arg Ile Val Ile Ile Asp Asp Ser Leu 1925 1930 1935 Tyr Glu Glu Glu Glu Thr Phe His Val Leu Leu Ser Met Pro Met Gly 1940 1945 1950 Gly Arg Ile Gly Ser Glu Phe Pro Gly Ala Gin Val Thr Ile Val Pro 1955 1960 1965 Asp Lys Asp Asp Gly Pro Ser Asp Ser Lys Phe Asn Val Ala Glu Asn 1970 1975 1980 Tyr Ser Leu Leu Pro Phe Thr Cys Phe Gin Gly Ser Ile Ala Thr Ala 1985 1990 1995 2000 Glu Ala Ala Thr Gin Gly Gly Gly Arg Ser Thr Arg Gin Val Ala Ala 2005 2010 2015 Val Lys Lys Asp Lys Asp Phe Lys Gly Lys Ala Gin Lys Gin Val Gin 2020 2025 2030 Phe Asn Pro Gly Gin Thr Arg Ala Thr Trp Arg Val Arg Ile Leu Ser 2035 2040 2045 Asp Gly Glu His Glu Gin Ser Glu Thr Phe Gin Val Val Leu Ser Glu 2050 2055 2060 Pro Val Leu Ala Ala Leu Glu Phe Pro Thr Val Ala Thr Val Glu Ile 2065 2070 2075 2080 Val Asp Pro Gly Asp Ala Cys Pro Trp Gly Glu Glu Ser Asp Gin Ser 2085 2090 2095 Ser Gin Gly Leu Lys Leu Gin Ser Phe Leu Thr Lys Met Met Val Ser 2100 2105 2110 Thr Asn Leu Leu Glu Asn Ser Phe Ser Arg Glu Asp Gin His Gin Glu 2115 2120 2125 Gin Leu Ser Arg Gin Lys Lys Trp Glu Ser Lys Thr Met Ile Ile Tyr 2130 2135 2140 66/79 Thr Phe Ile Leu Cys Glu Thr Glu Lys Pro Cys Ile Leu Glu Leu Met 2145 2150 2155 2160 Asp Asp Val Leu Tyr Glu Glu Val Glu Glu Leu Arg Leu Val Leu Gly S2165 2170 2175 0 Thr Pro Gln Ser Asn Ser Pro Phe Gly Ala Ala Val Gly Glu Gln Asn O 2180 2185 2190 Glu Thr Leu Ile Arg Ile Arg Asp Asp Ala Asp Lys Thr Val Ile Lys N 2195 2200 2205 Phe Gly Glu Thr Lys Phe Ser Val Thr Glu Pro Lys Glu Pro Gly Glu 2210 2215 2220 Ser Val Val Ile Arg Ile Pro Val Ile Arg Gin Gly Asp Thr Ser Lys 2225 2230 2235 2240 Val Ser Ile Val Arg Val His Thr Lys Asp Gly Ser Ala Thr Ser Gly 2245 2250 2255 C Glu Asp Tyr His Pro Val Ser Glu Glu Ile Glu Phe Lys Glu Gly Glu S2260 2265 2270 Thr Gln His Val Val Glu Ile Glu Val Thr Phe Asp Gly Val Arg Glu 2275 2280 2285 Met Arg Glu Ala Phe Thr Val His Leu Lys Pro Asp Glu Asn Met Ile 2290 2295 2300 Ala Glu Met Gin Leu Ser Asn Phe Glu Leu Thr Leu Ser Pro Asp Gly 2305 2310 2315 2320 Thr Arg Val Gly Asn His Lys Cys Ser Asn Leu Leu Asp Tyr Thr Glu 2325 2330 2335 Val Lys Thr His Tyr Gly Phe Leu Thr Asp Ala Thr Lys Asn Pro Glu 2340 2345 2350 Ile Ile Gly Glu Thr Tyr Pro Tyr Gin Tyr Ser Leu Ser Ile Arg Gly 2355 2360 2365 Ser Thr Thr Leu Arg Phe Tyr Arg Asn Leu Asn Leu Glu Ala Cys Leu 2370 2375 2380 Trp Glu Phe Val Ser Tyr Tyr Asp Met Ser Glu Leu Leu Ala Asp Cys 2385 2390 2395 2400 Arg Ser Val Leu Asn Ala Ser Ile Phe His Glu Met Ala Pro Glu Gly 2405 2410 2415 Lys Gin Ser Lys Cys Leu Val Asn Ser Thr Leu Tyr Ser Ile Leu Glu 2420 2425 2430 Cys His Glu Ser Leu Pro Asn Phe Cys Ile Ser Ala Leu Arg Met Gly 2435 2440 2445 Lys Trp Arg Lys Ile Lys Ser Lys Pro Ser Ala Gin Thr Pro Cys Ala 2450 2455 2460 Gin Arg Leu Arg Gly Phe Ile Asp His Pro Arg Lys Gin Pro Leu Gin 2465 2470 2475 2480 Gin Ala Ser Ala Asp Pro Gly Met Leu Pro Val Ile Ser Thr Arg Glu 2485 2490 2495 Leu Ser Asn Phe Glu Leu Thr Leu Ser Pro Asp Gly Thr Arg Val Gly 2500 2505 2510 Asn His Lys Cys Ser Asn Leu Leu Asp Tyr Thr Glu Val Lys Thr His 2515 2520 2525 Tyr Gly Phe Leu Thr Asp Ala Thr Lys Asn Pro Glu Ile Ile Gly Glu 2530 2535 2540 Thr Tyr Pro Tyr Gin Tyr Ser Leu Ser Ile Arg Gly Ser Thr Thr Leu 2545 2550 2555 2560 Arg Phe Tyr Arg Asn Leu Asn Leu Glu Ala Cys Leu Trp Glu Phe Val 2565 2570 2575 Ser Tyr Tyr Asp Met Ser Glu Leu Leu Ala Asp Cys Gly Gly Thr Ile 2580 2585 2590 Gly Thr Asp Gly Gin Val Leu Asn Leu Val Gin Ser Tyr Val Thr Leu 2595 2600 2605 Arg Val Pro Leu Tyr Val Ser Tyr Val Phe His Ser Pro Val Gly Val 67/79 2610 2615 2620 O Gly Gly Trp Gin His Phe Asp Leu Lys Ser Glu Leu Arg Leu Thr Phe 2625 2630 2635 2640 Val Tyr Asp Thr Ala Ile Leu Trp Asn Asp Gly Ile Gly Ser Pro Pro 0 2645 2650 2655 Glu Ala Glu Leu Gin Gly Ser Leu Tyr Pro Thr Ser Met Arg Ile Gly 2660 2665 2670 Asp Glu Gly Arg Leu Ala Val His Phe Lys Thr Glu Ala Gin Phe His N 2675 2680 2685 Gly Leu Phe Val Leu Ser His Pro Ala Ser Phe Thr Ser Ser Val Ile 2690 2695 2700 I n Met Ser Ala Asp His Pro Gly Leu Thr Phe Ser Leu Arg Leu Ile Arg 2705 2710 2715 2720 Ser Glu Pro Thr Tyr Asn Gin Pro Val Gin Gin Trp Ser Phe Val Ser C 2725 2730 2735 C Asp Phe Ala Val Arg Asp Tyr Ser Gly Thr Tyr Thr Val Lys Leu Val 2740 2745 2750 Pro Cys Thr Ala Pro Ser His Gin Glu Tyr Arg Leu Pro Val Thr Cys 2755 2760 2765 Asn Pro Arg Glu Pro Val Thr Phe Asp Leu Asp Ile Arg Phe Gin Gin 2770 2775 2780 Val Ser Asp Pro Val Ala Ala Glu Phe Ser Leu Asn Thr Gin Met Tyr 2785 2790 2795 2800 Leu Leu Ser Lys Lys Ser Leu Trp Leu Ser Asp Gly Ser Met Gly Phe 2805 2810 2815 Gly Gin Glu Ser Asp Val Ala Phe Ala Glu Gly Asp Ile Ile Tyr Gly 2820 2825 2830 Arg Val Met Val Asp Pro Val Gin Asn Leu Gly Asp Ser Phe Tyr Cys 2835 2840 2845 Ser Ile Glu Lys Val Phe Leu Cys Thr Gly Ala Asp Gly Tyr Val Pro 2850 2855 2860 Lys Tyr Ser Pro Met Asn Ala Glu Tyr Gly Cys Leu Ala Asp Ser Pro 2865 2870 2875 2880 Ser Leu Leu Tyr Arg Phe Lys Ile Val Asp Lys Ala Gin Pro Glu Thr 2885 2890 2895 Gin Ala Thr Ser Phe Gly Asn Val Leu Phe Asn Ala Lys Leu Ala Val 2900 2905 2910 Asp Asp Pro Glu Ala Ile Leu Leu Val Asn Gin Pro Gly Ser Asp Gly 2915 2920 2925 Phe Lys Val Asp Ser Thr Pro Leu Phe Gin Val Ala Leu Gly Arg Glu 2930 2935 2940 Trp Tyr Ile His Thr Ile Tyr Thr Val Arg Ser Lys Asp Asn Ala Asn 2945 2950 2955 2960 Arg Gly Ile Gly Lys Arg Ser Val Glu Tyr His Ser Leu Val Ser Gin 2965 2970 2975 Gly Lys Pro Gin Ser Thr Thr Lys Ser Arg Lys Lys Arg Glu Ile Arg 2980 2985 2990 Ser Thr Pro Ser Leu Ala Trp Glu Ile Gly Ala Glu Asn Ser Arg Gly 2995 3000 3005 Thr Asn Ile Gin His Ile Ala Leu Asp Arg Thr Lys Arg Gin Ile Pro 3010 3015 3020 His Gly Arg Ala Pro Pro Asp Gly Ile Leu Pro Trp Glu Leu Asn Ser 3025 3030 3035 3040 Pro Ser Ser Ala Val Ser Leu Val Thr Val Val Gly Gly Thr Thr Val 3045 3050 3055 Gly Leu Leu Thr Ile Cys Leu Thr Val Ile Ala Val Leu Met Cys Arg 3060 3065 3070 Gly Lys Glu Ser Phe Arg Gly Lys Asp Ala Pro Lys Gly Ser Ser Ser 3075 3080 3085 68/79 Ser Glu Pro Met Val Pro Pro Gin Ser His His Asn Asp Ser Ser Glu 3090 3095 3100 Val 3105 <210> 81 <211> 457 <212> PRT <213> homo sapiens <400> 8. MIet Gly Cys 1 Pro Ser Trp Ser Giy Ala Val Giu Val Giy Met Ala Leu Gly Gly Pro Ala Glu Asp Gly His 115 Leu Gly Ser 130 Ala Arg Ile 145 Gly Leu Thi Leu Leu Leu Thr Leu Ala 195 Ser Giu Pro 210 His Val Arg 225 Leu Gly Thr Gly Glu Gly Arg Arg Ile 275 Ala Giu Arg 290 Leu Thx Glu 305 Val Ser Tyr His Ile Leu Ala Ala Lys 355 Ser Ala Val Gin Val Leu Asp 300 Ile Cys Thr Pro Val 180 Asp Ser Leu Arg Glu 260 Leu Gin Ala Leu Gly 340 Ala Gly 5 Trp Trp Met Trp Ala Thr Pro His Tyr Ser 165 Pro Asp Pro Ala Glu 245 Arg Gin Trp Gly Pro 325 Leu Pro Ala Arg Ser Arg 70 Ser Gin Ser Trp Trp 150 Asp Gly His Glu Arg 230 Asp Leu Ala Lys Asp 310 Val Leu Arg Trp Lys Arg Val 55 Thx Trp, Asp Glu Asp 135 Gly Pro Gly Asp Val 215 Gin Val Phe Leu Lys 295 Ala Gly Gin Pro ly Met Ala 40 Thr Arg Asp Ser Gin 120 Phe Gin Gly Phe Val 200 Pro Leu Thr Asp Arg 280 Gin Ala Ile Glu Pro Leu Arg 25 Ser Gly Gly Gly Pro 105 Pro Arg Arg Glu Phe 185 Leu Pro Glu Pro Leu 265 Gly Leu Val Glu Glu 345 Gly Ser 10 Thr Val Leu Arg Ile 90 Ala Gly Asn Leu Phe 170 Gly Ser Gin Gly Lys 250 Glu Leu Gly Arg His 330 Leu Gin Cys Pro Pro Gly Gly 75 Gly Ile Asp Arg Arg 155 Cys Val Phe Pro Leu 235 Ser Glu Ser Pro Met 315 His Arg Pro Pro Ser Phe Arg His Ile Arg Gly Pro 140 Met Val Ser Leu Phe 220 Trp Asp Thr Lys Gin 300 Ala Phe Gly Pro Cys Met Ser Arg Val Phe Val Ala 125 His Ser Asp Ala .Thr 205 Leu Ala Ser Leu Gin 285 Ala Ala Leu Pro Axg Pro Arg Ala Gly Gly Phe Leu 110 Ser Pro Leu Val Ala 190 Phe Glu Arg Glu Gly 270 Leu Lys Glu Glu Ala 350 Ala Gin I Asn. Trp Ala Ser Asp Ala Gin Phe Asn Gly 175 Thr Ser Met Leu Ala 255 Arg Ala Pro Ala Leu 335 Lys Ser rhr Arg Glu Gin Val Ser Ser Gly Arg Ser 160 Pro Gly Leu Gin Gly 240 Gin His Gin Gly Gin 320 Asp Ala Ser 365 Cys Leu Gin Pro Gly Ile Phe Leu Phe Tyr Leu Leu Ile Gin Thr Val 69/79 Gly 385 Lys Asn Lys Tyr 370 Phe Th~r Leu Ser Gin 450 Phe Giy Tyr Val 390 Met Ala Phe Met 405 Thr Gly Ser Leu 420 Ala Ala Glu Ala 435 Lys Gin Leu Val 375 380 His Phe Axg Arg Pro Val Pro Arg Pro Ala 395 400 Val Lys Thx Met Val Gly Gly Gin Leu Lys 410 415 Gly Gly Gly Giu Asp Lys Gly Asp Gly Asp 425 430 Gin Gly Met Ser Arg Giu Giu Tyr Giu Giu 440 445 Giu Giu Lys 455 <210> 82 <211> 526 <212> PRT <213> homo sapiens <400> 82 Met Pro Ala Val Ser Gly Pro Gly Pro Leu Phe Cys Leu Leu I n Leu Leu2 Phe Giu Ala Giy Glu Glu Trp Ser Met Arg Trp Tyjr Ala Ser 130 Thr Gin 145 Pro Ser His Trp Tyr Trp, Ser Asp 210 Pro Gly 225 Asp His Pro Giu Ala Arg Giu Asp 290 Arg Leu 305 Iryr Ile V1al Arg Val Thr 115 Trp Asp Glu Asp Gly 195 Pro Gly Asp Val. G. 275 Val Pro Lys Pro Arg Ala Tlir 100 Arg Asp Ser Gin Phe 180 Gin Gly *Phe Val *Pro 260 Leu *Thr eu Phe Ser Gly Giy Gly Pro Pro 165 Arg Arg Giu Phe Leu 245 Pro Prc Ser Ser Trp, Thr 70 Val Leu Arg Ile Ala 150 Gly Asn Leu Phe Gly 230 Ser Gin Gly Lys IGlu 310 ?ro ?he Ser 55 Pro Pro Gly Gly Gly 135 Ile Asp Arg Arg Cys 215 Val. Phe Pro Sex 295 Lys C His I Ser Phe Arg His 120 Ile Arg Gly. Pro Met 200 Val Ser Leu Phe Trp 280 Asp 7hr ;iy is 4et Ser krg 105 V'al Phe Val Ala His 185 Ser Asp Ala Thi Lei 261~ Al~ Se~ Gly Pro2 Gly Arg Ala 90 Gly. Gly Phe Leu Ser 170 Pro Leu Val Ala Phe 250 Giu i Arg SGlu ys k.rg ksp Asn 75 Trp Ser Asp Ala 155 Gin Phe Asn Gly Thr 235 Ser Met Lei: Ala Pro Leu2 Ala Arg Giu' Gin Val Ser 140 Ser Gly Arg Ser *Pro 220 Gly *Leu *Gin Gly Gin 300 ?ro kla Ile Ser Vai Gly Leu 125 Pro Asp Leu Ala Gly 205 Leu Thr Sex His Let 28E G1~ Leu Leu Leu Giy Giu Met 110 Gly Ala Gly Gly Krg 190 *Leu *Leu Leu Giu Val 270 iGly SGiu ieu krg ?ro ;ay kia JIal A.la Gly Giu His Ser 175 Ile Thr Let Alf Prc 25~ Th Gil Leu Arg Gly Leu Val Gin Val Leu Asp Ile 160 Cys Thr Pro Val Asp 240 Ser ;Leu SArg ~Giu e Leu 320 Phe Asp Let Glu Thr Lei .i Gly Arg 315 70/79 His Arg Arg 11. IND 0 Gin Ala Leu Arg Gly Leu Ser Lys Gin Leu Ala Gin Ala Glu Arg Gin 325 Trp Trp Gly Leu 385 Asp Val Leu Arg Ile 465 Val Thr Gly Lys Ala His 370 Leu Ala Gly Gin Pro 450 Phe His Gly Ile Gin 340 Asp Ser Gly Val Glu 420 Glu Gly Phe Arg Leu 500 Arg Leu Ala Met Gin Arg 405 His Leu Gin Tyr Gin 485 Pro Arg Gly Ser Ser Trp 390 Met His Axg Pro Leu 470 Glu Leu Gin Gly 345 Ile Lys Leu Giu Giu 425 Ala Aia Gin Lys Ala 505 Pro 330 Gin Pro Asp Gin Ala 410 Leu Lys Ser Thr Ser 490 Pro Ala Ala Ser Ser Ala 395 Gin Asp Ala Ser Val 475 Leu His Ser Arg Thr Ala 380 Leu Vai His Al a Cys 460 Gly Gin Thr Met Pro Pro 365 Lys Gin Ser Ile Ala 445 Leu Phe Giu Pro Pro 525 Asp 350 Gly Val Giu Tyr Leu 430 Lys Gin Phe Cys Arg 510 Ala Gly Arg Gly Met Leu 415 Gly Ala Pro Gly Leu 495 Ala <210> 83 <211> 904 <212> PRT <213> homo sapiens <400> 83 Met Val Asn Val Thr Ala Ala Leu Leu Phe 145 Leu Giu Arg Leu Ser Gly Pro Phe Pro Lys Tbr Lys 130 Ser Pro Ile Val Leu Gly Phe Val Glu Leu Al a Phe 115 Asp Val Gin Phe Met Ala Gin Giy Ser Gly Ser Giu 100 Leu Asn. Ser Trp Ser 180 Thr Leu Leu Pro His Ala Val Val Asn, Gly Ser Phe 165 Val Pro Cys Giu Gin Pro Thr 70 Phe Thr Lys Ala Asn 150 Leu Asn Trp Ser His His 4 Val 55 Val Giu Leu Ser 135 Ile Lys Arg Ser Ser Ser 40 Leu Thr Gly Asn Ser 120 His Val Ala Gly Leu Gly 25 Giu Thr Leu Asp Thx 105 Asp Phe Lys Pro Pro 185 Ala 10 Asn Val Leu His Phe 90 Met Phe Thr Ile Asp 170 Leu Leu Tyr Vai Ser Ser Val Tyr His Gly Gin 155 Pro Leia Ile Tyr Ser Ser Ser Val Lys Ile Phe 140 Val Thr Thr Phe Cys Leu Al a Leu Leu Asn His 125 Asn Gin Val Gly Ala Thr Ser Giu Ile Arg Gly 110 His Gly Giu Ala Thr 190 Ala Ala Val Ala Leu Cys Asn Ala Ser His Leu 175 Gly Ile Tyr Phe Pro Thr Glu Asp Trp Asn Phe 71/79 Thr Leu Ile Pro Ile Thr Val Asp Asp Ala Cy Pro 225 Gin His Tyr Asn Gly 305 Gin Glu Glu Ala Asp 385 Lys Ser Glr Pro Pro 465 Ar Tin Prc Al~ Gi: 54 Th Se Pr Ar I 62 Se 210 Arg A Gln L Leu S Tyr M 2 Glu S 290 Gin G Asp I Met P His M 3 Tyr 370 Asn I Len C Phe I Leu Cys 450 Val J Val Thr 2 Gly a Arg 530 Glu 5 r Pro r Phe o Tyr g Arg 610 e Leu 5 *r Ser la Ts er et 75 er lu le 'he [et 55 la leu .ys 3eu Sex 135 1iE le Th Tn Asi 51! G1 Ly Me Ii Se 59 Ly Se As Pro T: Gly A~ 2 Len I 260 Glu L Arg S Ala A Phe I 3 His G 340 Ser V Asp G Ser I Pro 1 Arg I 420 Phe Gin Ser Len 500 i Thr 5 y Sen s Glu t Sen e Ala 580 r Val 5 'S Glu !r Ile ;n Asn rp G: 2: sn P: 45 le T eu G er P sp G 3 ie 25 in V 'al T 3iy I) 'no ?he I 105 kla I Pro Jal Val Thr 485 His Len Pro Asp Arg 565 Pro Phe Lys lu 30 ro hr ly yr in 10 lyr 'al Irp 'rp jer 390 jeu ys Prc Let His 47 CY Art GI Ar Cy 55 Ly Al GI Le 215 Val Asp Len Glu His 295 Lys Ile Tyr Ala Leu 375 Thr Ala Lye VaJ i PrC 45 Prc s As g Hi u Va g Se 53 s Va 0 s Ar a Le u Gl un T1 61 Gly Leu Phe Lys 280 Trp Len Arg Arg Len 360 Phe Gin Ile Ser Glu 440 SArg Pro n G11 s Ty3 1 Are 524 r As 5 1 Se g Se: n An .y As 60 Ir Al -5 Ser Len Cys 265 Lys Phe Trp Gin Arg 345 Arg Thr Ser Gly Len 425 Asp Asn Tr p r PhE Tx 501 Glt a Prc r AsI r Se g Le 58 p Th 0 a Va r Tn TAr Leu T1 23 Met G3 250 Asn ME Asp A Gin L Phe P: 3 Gly G 330 Pro A Val A Len P Gin T 3 Pro P 410 Val P Leu I Ile I Thr '1 SGin I 490 Gly i Sen o Val Lys r Cys 570 u Asp 5 r Leu 1 Lys p Asp g Cys 650 's Ile 72/79 1 ui 3 1 1 1 ,1 c r r s Lys Arg Pr 220 r Pro Gly Ly 5 y Pro Phe As t Ala Gly SE 2', .a Len Phe VE 285 r* Phe Ser L 300 :o Pro Gly L L5 Lu Sen Cys L La Giy Gly V 3 sn Sen Ser G 365 te Gin Len G 380 hr His Glu G 95 no Ala His S la Tyr Ile I 4 eu Pro Lys S 445 la Ala Ala 2 460 hr Phe Phe I ,75 he Tyr Ala nlu Lys Len ;ly Len Tyr 525 krg Len Len 540 ksn Pro Ala 555 Ser Sen Len Sen Leu Ile Val Len Arg 605 Tyr Thr Trp 620 Len Leu Ile 635 Ile Gly Tyr Ile Lys Ile o Cys Ala '5 Ii rl 1l in eu eu ly ln ly ;er )ys ezr Chi Ph: 51 9r( Ph Th Se Le 59 CY AS Pr GI G1 Sen P1, 24 Val LE 255 Len P1 Thr G3 Ala G Met Si 3: Val I 335 Pro V Len P Ser V His G 4 Arg G 415 Gly P Gin I His I GlyC SGlui 495 r Len g Cys 4 e Ser r Asn r Ala 575 n Gin 0 s His n Gly o Gin Ly Asp 655 Ln Gly Ly uu le ly er le al lu 00 ily sn 'rp 'ys ;lu 180 ys rhr Gln Ser His 560 Thr Ala Arg Asn Ala 640 Glu Ile Sen Asn Lys 630 Asn Gly Asn 645 Se TY Asn Asp Val Phe Arg Ser Asn Phe L Pro Val Ser Gly. Val Leu Leu Giu Thr Gin Pro Ser 675 680 Val. Gly 705 Gly Ile Tyr Pro Leu 785 Arg Ile Lys Arg Gly 865 Val Ile Glu 690 Asp Arg Arg Gly Gly 770 Ser Arg Gin Asn Ala 850 Ala Tyr Ser Gly Thr Lys Gin Pro 755 Asn Ala Lys Thr Gin 835 Cys Asn Ser Ser Giu Thr Thr Ser 740 Val Arg Leu Ser Thr 820 Glu Ile Thr Giu Lys 900 Met Leu Phe Ser 710 Gin Arg 725 His Ala Gin Ser Asp Gly Leu Leu 790 Val His 805 Gin Leu Leu Glu Trp Ser Ser Arg 870 Vai Lys 885 Asp Glu Val 695 Trp Ser Giy Met Leu 775 Ala Pro Gly Leu Thr 855 Thr Thr Glu Leu Val Cys His Arg Giu Leu Arg Ala 730 Gly Tyr Tyr 745 Val Leu Asn 760 Val. Ala Ala Val. Ala Leu Lys Lys Gly 810 Giu Giu Glu 825 Val. Asn Val 840 Leu Met Gly Leu Leu Glu Gin His Pro 890 Ser Ser Asp 715 Giu Cys Val Gly Leu 795 Asp Giu Gly Thr Asp 875 Va. 700 Met Leu Thr Thr Al a 780 Phe Leu Gly Glu Cys 860 Lys Gly 685 Ala Gin Glu Ala Val 765 Thr His Val. Asn Ser 845 Gin Asp Giy Gin Ala Asp 750 Arg Gly Cys Tyr His 830 Phe Thr Val Gly Ser Pro 735 Asn G).u Gly Trp, Ser 815 Gly Ser Ile Ser Thr Leu 720 Ala Ser Thr Leu Arg 800 Giu Asn His Gly Val 880 Asp Asn Ser Ala Giy Lys 895 <210> 84 <211> 515 <212> PRT <213> homo, sapiens <400> 84 Met Ser Thr Phe Glu Gly Mrg Val Glu Ile 145 Leu Ala Phe Tyr LYS Leu Leu Phe Lys 130 Ser Leu Ala Phe Ala Leu Tyr Leu Glu 115 Leu Asn Trp, Ala Lys Thr Thr Mrg Phe 100 Gly Thr Lys Ala His Gly Glu Leu Cys Ser Asp Ala Ser Ser Lys Giu Lys Thr 70 Gin Ser Thx Val Trp Leu Pro AMg Thr 55 Pro Ala Asp Leu Lys 135 Asp Leu Va. Val 40 Thr Gly Arg Ser Val 120 Tyr Leu Ala Ile 25 Th~r Trp, Asn Gly Leu 105 Leu Thr Leu Phe Ala Ser Va. Leu Thr Tyr His Thr Leu 75 Ser Pro 90 Ile Leu Mrg Cys Trp Asn Ile Pro 155 Pro His Cys Mrg Giu Mrg Gin His Gly 140 Gin Val Pro Asn His Val Ser Ala Mrg 125 Asn Ala Cys Pro Gly Tyr Mrg Asn Pro 110 Mrg Ile Ser Gly Trp Phe Trp, Giu Pro 95 Mrg Leu Ser Gin Thr Gin Gly Ser Va. Ser Lys Ser Asn 160 150 Asn Asn Gly Asn Tyr Arg Cys Ile Gly Tyr Giy Asp Giu Asn Asp Va. 73,79 Phe I Pro C Asn Leu I 225 Ser Gly His Val Met 305 Phe Gin His Gin Asp 385 Leu Gly Pro Ser Glu 465 Arg Lys Glu -xg lu .eu 210 iis rhr Ser Ser Leu 290 Leu Ser Arg Ala Ser 370 Gly Leu Val Gly Leu 450 Ile Thr Thr Glx Ser Asn I 180 Leu Lys 195 Ser Cys Phe Asn Tyr Pro Tyr Trp 260 Pro Ser 275 Leu Glu Val Leu Trp His Ser Leu 340 Gly Gly 355 Met Val Leu Val Ala Val Gly Phe 420 Glu Ser 435 Tyr Val Gin Thr Leu Leu Gin His 500 Ser 515 165 Phe kla Glu Phe Glu 245 Cys Leu Thr Val Arg 325 Arg Tyr Leu Ala Ala 405 Leu Ser Asp Thr Glu 485 Lys I Thr Thr C Phe I 230 Leu Gly Gin Gin Cys 310 Glu Ala Tyr Asn Ala 390 Leu Gly His Val Gin 470 Asp :le Lsp ;In !15 krg .In k1a Ile Pro 295 Ser Asp Glu Cys Val 375 Gly Leu Asp Ser His 455 Leu Lys Ile Ser 200 Leu Asp Leu Glu His 280 Ser Val Met Leu Thr 360 Thr Ala Phe Glu Ile 440 Pro Gly Asp 1,ys L85 3I Pro Giy Pro Thr 265 Val Gly Ala Gin Glu 345 Ala Val Thr His Thr 425 Cys Lys Gli Val 170 Ile C Pro Pro Glu Thr 250 Val Gin. Gly I Glu Glu 330 Leu Asp Arg Gly Cys 410 Arg Pro Lys 1 Glu Ser 490 ;In Phr 3lu Jal 235 Val Arg Arg Gin Gly 315 Ser Pro Asn Glu Gly 395 Trp Leu Ala Gly Glu 475 Val Glu Glu Arg 220 Ile Trp Gly Ile Ala 300 Thr Leu Ala Ser Thr 380 Leu Arg Pro Gin Asp 460 Glu Val Leu I Gly 2 205 Ser I Leu Arg Asn Pro 285 Val Gly Gly Ile Tyr 365 Pro Leu Arg Pro Val 445 Leu Ala Tyr ?he ~sn ksp Ser Glu Ile 270 Val Glu Asp Arg Arg 350 Gly Gly Ser ArG Ala 43C GliL Va Asr Set 175 Pro Ser Thr Asp Asn 255 His Ser Gly Thr Lys 335 Gin Pro Asn Ala Lys 415 Pro i Let L Tya Th.3 r Git His Val Pro Trp 240 Ser Lys Gly Glu Thr 320 Thr Ser Val Arg Leu 400 Ser Gly Gin Ser Ser 480 i Val 495 Pro Asp Asn Ser Ala Gly Lys Ile Ser Ser Lys Asp <210> <211> 831 <212> PRT <213> homo sapiens <400> Asx Met Ala Val Gly Gly Gly His Lys Gly Val Arg Cys Pro Pro Ser 1 5 10 Ala Arg Ser Ser Gin Val Pro Thr Cys Cys Ala Gly Trp Arg Gin Gin 25 Gly Asp Giu Cys Gly lie Ala Vai Cys Giu Giy Asn Ser Thr Cys Ser 40 74/79 Giu Asn Glu Val Cys Val Arg Pro Gly Glu Cys Arg Cys Arg His Gly 55 Tyr Pro Asp Cys Gly Ala 145 Cys Ala Arg Arg Tyr 225 Leu Thr Thr Ser Thr 305 Glu Cys Leu Pro Asp 385 Arg Leu Pro Lys Leu 465 Ala Pro Phe Asp Val Glu Ala 130 Cys Leu Cys Glu Gly 210 Arg Gly Val Lys His 2'90 Gly Thr Ala Cys Gly 370 Thr Lys Leu Thr Ala 450 Pro His Ser Gly Cys Thr His 115 Cys Tyr Cys Asn Arg 195 Arg Gly Cys Ala Cys 275 Arg Lys Lys Asp Ser 355. Leu Cys Gly Leu Arg 435 Pro Arg His Gly Ala Lys Gly 100 Ala Arg Cys His Ser 180 Thx Cys Lys Arg Glu 260 Asp Cys Cys Cys Cys 340 Pro His Asp Val Ser 420 Arg His Ile Asp Leu 500 Asn Giu Gin cys Cys Ser Ala 165 Ser Phe His Tyr Arg 245 Gly Gin Pro Thr Ser 325 Gly Gly Gly Pro Met 405 Leu Pro Arg Pro Leu 485 Glu Cys 70 Leu Cys Gin Giu Ala 150 Gly Pro Gly Pro Cys 230 Arg Arg Pro Pro Arg 310 Asn Ser Val Ala Val 390 Gly Leu Arg Leu Leu 470 Asp Gin Asp Cys Thr Cys Ser 135 Thr Trp, Cys Ala Val 215 Arg Cys Cys Cys Cys 295 Cys Gly Gly His Asp 375 Thr Ala Gly Pro Cys 455 Arg Asn Pro Thr Ser Cys Gin 120 Gly Ser Trp Glu Arg 200 Asp Glu Gly Leu Ala 280 Arg Asn Thr His Gly 360 Cys dly Gly Cys Arg 440 Giy Arg Thr Ser Lys Cys His 105 His Trp Arg Gly Gin 185 Cys Gly Pro Gin Thr 265 Thr Asp Ala Tyr Cys 345 Pro Ala Ala Ala Cys 425 Arg Arg Gin Leu Pro :Cys His 90 Ala Gly Trp Cys Arg 170 Gin Asp Thr Cys Cys 250 Cys Gly Gly Gly Gly 330 Asp His Gin Cys Leu 410 Cys Glu Phe Lys Asn 490 Sex Pro 75 Pro Ar g Thr Gly Asp 155 Ser Ser Arg Cys Pro 235 Lys Glu Phe His Trp 315 Glu Phe Cys Ala His 395 Leu Ala Leu Ser Leu 475 Cys Trp Axg His Arg Cys Ala 140 Pro Cys Gly Tyr Al a 220 Ala Gly Pro Tyr Ala 300 le Asp Gin Asn Cys 380 Leu Val Cys Ser Arg 460 Pro Sex Ser Gin Gly Trp His 125 Gin Gin Asn. Arg Cys 205 Cys Gly Gin Gly Gly 285 Cys Gly Cys Ser Val 365 Sex Giu Leu Arg Leu 445 le Lys Phe Ser Phe 'ln Gly 1.10 Pro Thr Asn Cys 190 Gin Glu Phe Gin Trp 270 Giu Asn Asp Ala Gly 350 Thr Cys Thr Leu Gly 430 Gly Ser Val Leu Arg Trp Cys Ala. Arg Ala Gly. Gin 175 Gin~ Cys Pro Tyr Pro 255 Asn Gly His Arg Phe 335 Arg Cys His Asn Val 415 Lys Axg Met Val Glu 495 Ala Gly Glu Arg Ser Ser Ala 160 Cys Cys Phe Gly Gly 240 Cys Gly Cys Val Cys 320 Val Cys Pro Glu Gin 400 Cys Asp Lys Lys Val 480 Pro Ser 510 Phe Ser Sex Phe Asp Thr Thr Asp Glu Gly Pro Val Tyr Cys Val Pro 75,79 His Glu Glu Ala Pro Ala Glu Ser Arg Asp Pro Glu Val Pro Thr Val Pro 545 Ser Ser Ala Leu Pro 625 Ala Ala His Pro Pro 705 Arg Ala Leu Lys Glu 785 Thr 530 Ala Ala Ala Arg Ser 610 Ala Ala Pro Thr Pro 690 Arg Arg Asp Gly Arg 770 Thr Pro Glu Glu Ser Arg 595 Leu Thr Ala Ser Val 675 Gly Ala Arg Val Ala 755 Ser SPro SArg Ala Glu Ser 580 31u Ser Lys Gly Pro 660 Glu Leu Arg Ser Arg 740 Gin Val Gly Lys Ala 820 Pro Ala 565 Val Ala Pro Pro Arg 645 Ser His Pro Ala Pro 725 Gly Gly Pro Pro Lys 805 Ala 550 Ile Glu Arg Ser Lys 630 Ala Lys Gly Glu Arg 710 Ala Lys Pro Pro Glu 790 Thr 535 Pro Pro Gly Pro Pro 615 Val Pro Arg Ser Glu 695 Ala Lys Thr Arg Ala 775 Lys Pro Ser Leu Pro Ala 600 Glu Ser Ser Lys Pro 680 Ala Ala Arg Arg Glu 760 Ser Ala Ile Pro Pro Gly 585 Arg Arg Trp Pro Arg 665 Arg Thr Pro Ala Ser 745 Lys Pro Ala Gin Arg 825 Val Ala 570 Gly Ala Arg Ile Pro 650 Thr Thr Ala Arg Glu 730 Leu Pro Ala Thr Lys 810 Pro 555 Ser Ala Arg Lys His 635 Pro Pro Arg Leu Pro 715 Ala Gly Ala Arg Asp 795 Prc 540 Leu Ser Leu Gly Pro 620 Gly Pro Ser Asp Ala 700 Leu Ala Arg Pro Ala 780 SLeu SPro Thr Asp ryr Glu 605 Pro Lys Gly Asp Pro 685 Ala Gly Ser Ala Pro 765 Pro Pro Arg Thr Ser Ala 590 Ile Pro His Ser Lys 670 Thr Pro Ala Met Glu 750 Gin Pro Ala Lys Pro Glu 575 Arg Gly Pro Ser Glu 655 Ser Pro Ser His Leu 735 Val Lys SAla Pro SLys 815 Ala 560 Arg Val Gly Asp Ala 640 Ala Ala Arg Pro Gly 720 Ala Ala Ala Thr Glu 800 Ser Arg Glu Ala Gly Glu Leu Gly Ala Gly Ala Pro Thr Leu 830 <210> 86 <211> 871 <212> PRT <213> homo sapiens <400> 86 Asx Met Glu Gly Ala 1 5 Gly Ala Gly Gly Pro Leu Leu Leu Trp Met Pro Arg Gly Arg Asn Cys Cys Ala Gly Trp Cys Glu Gly Asn Ser Gly Pro Leu Val Arg 70 Thr Pro Ser Pro Cys 55 Gin Cys Arg Pro Asp 40 Arg Gin Ser Gly Ala Gly 10 Leu Leu Pro 25 Thr Val Ala Ala Pro Gly Gly Asp Glu 75 Glu Asn Glu 90 76/79 Pro Ser Pro Ser Cys Val Ala Leu Gin Gin Gly Cys Arg Leu Glu Val Ile Val Arg Leu Leu Pro Ala Arg Arg Leu Asn Thr Val Pro Giy Glu Cys Arg Cys Arg His Gly Tyr Phe Gly Ala Asn Cys Asp Thr 100 105 110 Lys Cys His2 145 His Trp Arg Gly Gin 225 Cys Gly Pro GIn Thr ~305 Thr Asp Ala Tyr Cx's 385 Pro Ala Ala Ala Cys 465 Arg Arg Gin Leu Pro 545 -ys 5i 130 kla ly rrp -Cys k.rg 210 Gln Asp Thr Cys Cys 290 Cys Gly Gly Gly Gly 370 Asp His Gin Cys Leu 450 Cys Glu PhE Lys Asr 53 C Sea Pro Pro Arg Thr Gly Asp 195 Ser Ser Arg Cys Pro 275 L~ys Giu Phe Hi-s Trp 355 Giu Phe Cys Ala *His 435 Leu *Ala Leu Ser Leu 515 iCys -Trp, krg Hi Arg x's Alia 180 Pro Cx's Gly Tyr Ala 260 Al a Gly Pro Tyr Ala 340 Ile Asp Gin Asn Cys 420 Leu Val Cys Ser Arg 500 Pro Ser Ser Gin Gix' Trp His 165 Gin Gin Asn Arg Cys 245 Cx's Gly Gin Giy Gly 325 Cys Gly Cys S er Val 405 Ser Giu Leu Ang Lea 485 Ile Lys *Phe *Sex Phe 9) Gin Gly2 150 Pro2 Cx's2 Thr Asn Cx's 230 Gin Giu Phe Gin Trp 310 Giu Asn Asp Aia Gly 390 Thr Cys Th~r *Leu *Gly 470 *Gix' Ser Val Leu Arg 550 ~rp 'Ys L3 5 kUa Lrg kla 31Y 215 Gln Cx's Pro Tyr Pro 295 Asn Gly His Arg Phe 375 Arg Cx's His Asn Vai 455 Lys Arg Met Val Glu 535 Ala Gly 120 Giu Arg Ser Ser Ala 200 Cx's Cx's Phe Gly Gly 280 Cys Gly Cx's Val Cx's 360 Val Cx's Pro Gir 440 Cys Asi *Lys *Lyl Va 52 Pr Se Pro Asp Cx's Gly Ala 185 Cx's Ala Arg Arg Tyr 265 Leu Thr Thr Ser Thbr 345 Giu Cys Leu Pro Asp 425 Arg Leu )Pro Ly's Leu 505 1Ala Pro Phe ksp Val G1u Ala 170 Cys Leu Cx's Giu Gix' 250 Arg Gix' Vai Lys His 330 dly Thr Ala Cx's Gly 410 Tbx Lys Leu Thr Ala 490 Prc His Sea Sea Cx's L Thr C 1 His 2 155 Cys Tyr(c Cx's I Asn Arg 235 Ang Gly Cx's Ala Cx's 31i5 Axg Lys Lys Asp Ser 395 Leu Cys Gly Leu *Ang 475 Pro Ang His *Gix' *Ser 555 'xs 1l a rg ~ys ~i s 'er Phr -'ys k.rg Glu 300 A~sp cx's Cys Cys Cys 380 Pro His Asp Val Ser 460 His Ile Asj LeL 540 PhE Giu 1 125 GinC Cys Cys Ser2 Ala 205 Ser Phe His Tyr' Arg 285 Gix' Gin Pro Thr Ser 365 Gly Gly Giy Pro Met 445 Leu Pro Arg Pro Leu 525 1Giu Asp jeu "hs In ;lu kla 190 3 1 y Pro Pro Cx's 270 A.rg Arg Pro Pro Arg 350 Asn Ser Val Ala Val 430 Gix' Leu Ar g Leu Leu 510 Gin Thr Cys Thr Cys Ser 175 Thr Trp Cys Ala Val 255 Arg Cys Cx's Cys Cys 335 Cys Glx' Gly His Asp 415 Thr Ala Gly Pro Cys 495 Arq Asr LPrc Thu Ser Cx's Gin 160 Gix' Ser Trp, Giu Arg 240 Asp Glu Gly Leu Ala 320 Arg Asn Thr His Gly 400 *Cx's Gly *Gix' -Cys Ang 480 Gly Arg 1Thr Ser Asp 560 Giu Gix' Pro Val Tyr Cx's Val Pro His Glu Giu Aia Pro Ala G].u Ser 77/79 565 Val Pro Arg Asp Pro Glu Thr Val Pro Pro Pro Gly 625 Arg Arg Trp Pro Arg 705 Arg Thr Pro Ala Ser 785 Lys Pro Ala Gin Arg 865 Jal Ala 610 Gly Ala Arg Ile Pro 690 Thr Thr Ala Arg Glu 770 Leu Pro Ala Thr Lys 850 Pro 595 Ser Ala Arg Lys His 675 Pro Pro Arg Leu Pro 755 Ala Gly Ala Arg Asi 83 Pr 580 Leu Ser Leu Gly Pro 660 Gly Pro Ser Asp Ala 740 Leu Ala Arg SPro Ala 820 SLeu o Pro rhr Asp Pyr Glu 545 Pro Lys Gly Asp Pro 725 Ala Gly Ser Ala Pro 805 Pro Pro Arg Thr Ser Ala 630 Ile Pro His Ser Lys 710 Thr Pro Ala Met Glu 790 Gin Pro Ala Lys Pro Glu 615 Arg Gly Pro Ser Glu 695 Ser Pro Ser His Leu 775 Val Lys Ala Pro Lys 855 Ala 600 Arg Val Gly Asp Ala 680 Ala Ala Arg Pro Gly 760 Ala Ala Ala Thr SGlu 840 585 Ser Ser Ala Leu Pro 665 Ala Ala His Pro Pro 745 Arg Ala Let Lys Gl 825 Thl 570 Ala C Ala C Ala Arg Ser 650 Ala Ala Pro Thr Pro 730 Arg Arg SAsp Gly SArg 810 i Thr 5 r Pro lu Ser xrg 635 Leu Thr Ala Ser Val 715 Gly Ala Arg Val Ala 795 Ser Pro Arg 575 Pro Ser Glu 1 Ser 620 Glu Ser Lys Gly Pro 700 Glu Leu Arg Ser Arg 780 Gin Val SGly Lys Ala 860 Ala 605 Val Ala Pro Pro Arg 685 Ser His Pro Ala Pro 765 Gly Gly Pro Pro Lys 845 590 Ile Glu Arg Ser Lys 670 Ala Lys Gly Glu Arg 750 Ala Lys Pro SPro Glu 830 Thr Pro l1y Pro Pro 655 Val Pro Arg Ser Glu 735 Ala Lys Thr Arg Ala 815 Lys Pro Leu Pro Ala 640 Glu Ser Ser Lys Pro 720 Ala Ala Arg Arg Glu 800 Ser Ala Ile Glu Ala Pro Ala i Ser Arg Glu Ala Gly Glu Leu Gly Ala Gly Ala Pro Thr Leu 870 <210> 87 <211> 134 <212> PRT <213> homo sapiens <400> 87 Ile Asp Cys Arg Ala Glu Gin 1 5 Gly Leu Pro Asp Pro Ala Leu Glu Gin Gly Ala Ala Val Asn Leu Ser Leu Ala Cys Glu Arg 55 Val Gin Phe Ser Gly Asp Pro 70 Pro Val Met Trp Ala Ala Ala Gly Arg Leu 40 Gly Glu Cys Arg Thr 10 Ala Arg 25 Arg Asp His Leu Ala Ala Gly His 90 78/79 Pro Phe Glu Asp Asp 75 Gly Leu Val Arg Ala Ser Ala Met Arg Gly Val Ala Val Val Ala Leu Leu Arg Thr Gin Leu Gly Asn Leu Glu Val Leu Ala Leu Ser Phe Leu Val Arg Ser Phe Arg Arg Leu Gly Leu Arg Leu Asp Arg Thr Asn 100 105 110 Arg Ala Gly Leu Thr Ala Leu Gln Leu Ala Ala Ala Arg Gly His Gly 115 120 125 Thr Cys Val Gin Ala Leu 130 <210> 88 <211> 324 <212> PRT <213> homo sapiens <400> 88 Met Leu Lys Pro Lys Asp Leu Cys Pro Arg Ala Gly Thr Arg Thx Phe 1 Leu Glu Ala 5 Asp. Thr Arg Asp Leu Ala His Leu 145 Ala Ala Glu Thr Pro 225 Val Ser Arg Gly Val 305 Ala Pro Phe Glu Asp Asp Gly 130 Arg Ala Gly Arg Glu 210 Asn Leu Pro Arg Pro 290 Pro Leu Leu Val Arg Ala Ser 115 Ala Leu Ala Ser Pro 195 Glu Ser Glu His Ser 275 Glu Gly Met Asp Met Arg Gly Val 100 Ala Val Asp Arg Ala 180 Glu Glu Pro Gly Pro 260 Thr Ser Pro Gin Arg Val Leu Arg Gin Gly. Leu Arg Gly 165 Gly Leu Ala Gin Ala 245 Glu Ala Gly k1a Ser Ala Leu 70 Thr Leu Asn Glu Thr 150 His Lys Gly Ala Ser 230 Pro Gly Pro Pro Gly Ile Val 55 Leu Ala Leu Ser Phe 135 Asn Gly Asn Arg Arg 215 Ser Pro Gly Asp GlL 295 Lys Ile 40 Gly Glu Leu Val Pro 120 Leu Arg Thr Ser Ser 200 Leu Gly Thr Pro Ile 280 Leu Val 25 Asp Leu Gin Ser Gin 105 Val Vai Ala Ser Gly 185 Met Arg Thr Leu Gi. 265 Pro Glt His Cys Pro Gly. Leu 90 Phe Met Arg Gly Ala 170 Arg Ser Ala Gly Ala 250 Ser Ser Ala Leu A.rg Asp Ala 75 Ala Ser Trp Ser Leu 155 Gly His Leu Gly Arg 235 Gin Gly Leu Asr Ala Ala Pro Ala Cys Gly. Ala Phe 140 Thr Gly Arg Ala Ala 220 Trp Ala Arg Val Ala 300 krg 3lu Ala Vral Glu Asp Ala 125 Arg Ala His Ala Leu 205 Leu Arg Pro Leu Gly 285 Leu Phe Gin Leu Asn Arg Pro 110 Ala Arg Leu Gly Gin 190 Gly Met Ser Ile Gly 270 Glu Ser Val Gly Arg Leu Gly Glu Cys Leu Gin Gly 175 Gly Ala Ala Gin Gly 255 Leu Ala Val ,eu krg Ala Arg His Ala Gly Gly Lea 160 Glu Ser Val Leu Glu 240 Leu Arg Pro Sex Asn Pro Trp Gin Ala Gly Thr Glu Ala Val Val Leu Arg Ala Gin Arg 79/79