CA2380549A1 - Secretory molecules - Google Patents

Abstract

The present invention provides purified secretory polynucleotides (sptm). Also encompassed are the polypeptides (SPTM) encoded by sptm. The invention also provides for the use of sptm, or complements, oligonucleotides, or fragments thereof in diagnostic assays. The invention further provides for vectors and host cells containing sptm for the expression of SPTM. The invention additionally provides for the use of isolated and purified SPTM to induce antibodies and to screen libraries of compounds and the use of anti-SPTM
antibodies in diagnostic assays. Also provided are microarrays containing sptm and methods of use.

Description

SECRETORY MOLECULES
TECHNICAL FIELD
The present invention relates to secretory molecules and to the use of these sequences in the s diagnosis, study, prevention, and treatment of diseases associated with cell signaling.
BACKGROUND OF THE INVENTION
Protein transport and secretion are essential for cellular function. Protein transport is mediated by a signal peptide located at the amino terminus of the protein to be transported or so secreted. The signal peptide is comprised of about ten to twenty hydrophobic amino acids which target the nascent protein from the ribosome to a particular membrane bound compartment such as the endoplasmic reticulum (ER). Proteins targeted to the ER may either proceed through the secretory pathway or remain in any of the secretory organelles such as the ER, Golgi apparatus, or lysosomes.
Proteins that transit through the secretory pathway are either secreted into the extracellular space or is retained in the plasma membrane. Proteins that are retained in the plasma membrane contain one or more transmembrane domains, each comprised of about 20 hydrophobic amino acid residues.
Proteins that are secreted from the cell are generally synthesized as inactive precursors that are activated by post-translational processing events during transit through the secretory pathway. Such events include glycosylation, proteolysis, and removal of the signal peptide by a signal peptidase.
2o Other events that may occur during protein transport include chaperone-dependent unfolding and folding of the nascent protein and interaction of the protein with a receptor or pore complex.
Examples of secretory proteins with amino terminal signal peptides are discussed below and include proteins with important roles in cell-to-cell signaling. Such proteins include transmembrane receptors and cell surface markers, extracellular matrix molecules, cytokines, hormones, growth and 2 s differentiation factors, neuropeptides, vasomediators, ion channels, transporters/pumps, and proteases. (Reviewed in Alberts, B. et al. (1994) Molecular Biology of The Cell, Garland Publishing, New York, NY, pp. 557-560, 582-592.) G-protein coupled receptors (GPCRs) comprise a superfamily of integral membrane proteins which transduce extracellular signals. Not all GPCRs contain N-terminal signal peptides. GPCRs 3 o include receptors for biogenic amines such as dopamine, epinephrine, histamine, glutamate (metabotropic-type), acetylcholine (muscarinic-type), and serotonin; for lipid mediators of inflammation such as prostaglandins, platelet activating factor, and leukotrienes; far peptide hormones such as calcitonin, CSa anaphylatoxin, follicle stimulating hormone, gonadotropin releasing hormone, neurokinin, oxytocin, and thrombin; and for sensory signal mediators such as retinal 35 photopigments and olfactory stimulatory molecules. The structure of these highly conserved receptors consists of seven hydrophobic transmembrane regions, cysteine disulfide bridges between the second and third extracellular loops, an extracellular N-terminus, and a cytoplasmic C-ternunus.
The N-terminus interacts with ligands, the disulfide bridges interact with agonists and antagonists, and the large third intracellular loop interacts with G proteins to activate second messengers such as cyclic AMP, phospholipase C, inositol triphosphate, or ion channels. (Reviewed in Watson, S. and Arkinstall, S. ( 1994) The G-protein Linked Receptor Facts Book, Academic Press, San Diego, CA, pp. 2-6; and Bolander, F.F. (1994) Molecular Endocrinolosy, Academic Press, San Diego, CA, pp.
162-176.) Other types of receptors include cell surface antigens identified on leukocytic cells of the immune system. These antigens have been identified using systematic, monoclonal antibody (mAb)-lo based "shot gun" techniques. These techniques have resulted in the production of hundreds of mAbs directed against unknown cell surface leukocytic antigens. These antigens have been grouped into "clusters of differentiation" based on common immunocytochemical localization patterns in various differentiated and undifferentiated leukocytic cell types. Antigens in a given cluster are presumed to identify a single cell surface protein and are assigned a "cluster of differentiation" or "CD"
designation. Some of the genes encoding proteins identified by CD antigens have been cloned and verified by standard molecular biology techniques. CD antigens have been characterized as both transmembrane proteins and cell surface proteins anchored to the plasma membrane via covalent attachment to fatty acid-containing glycolipids such as glycosylphosphatidylinositol (GPn.
(Reviewed in Barclay, A. N. et al. (1995) The Leucocyte Antigen Facts Book, Academic Press, San zo Diego, CA, pp. 17-20.) Matrix proteins (MPs) are transmembrane and extracellular proteins which function in formation, growth, remodeling, and maintenance of tissues and as important mediators and regulators of the inflammatory response. The expression and balance of MPs may be perturbed by biochemical changes that result from congenital, epigenetic, or infectious diseases. In addition, MPs affect z s leukocyte migration, proliferation, differentiation, and activation in the immune response. MPs are frequently characterized by the presence of one or more domains which may include collagen-like domains, EGF-like domains, immunoglobulin-like domains, and fibronectin-like domains. In addition, MPs may be heavily glycosylated and may contain an Arginine-Glycine-Aspartate (RGD) tripeptide motif which may play a role in adhesive interactions. MPs include extracellular proteins 3o such as fibronectin, collagen, galectin, vitronectin and its proteolytic derivative somatomedin B; and cell adhesion receptors such as cell adhesion molecules (CAMs), cadherins, and integrins. (Reviewed in Ayad, S. et al. (1994) The Extracellular Matrix Facts Book, Academic Press, San Diego, CA, pp. 2-16; Ruoslahti, E. (1997) Kidney Int. 51:1413-1417; Sjaastad, M.D. and Nelson, W.J. (1997) BioEssays 19:47-55.) 35 Cytokines are secreted by hematopoietic cells in response to injury or infection. Interleukins, neurotrophins, growth factors, interferons, and chemokines all define cytokine families that work in conjunction with cellular receptors to regulate cell proliferation and differentiation. In addition, cytokines effect activities such as leukocyte migration and function, hematopoietic cell proliferation, temperature regulation, acute response to infection, tissue remodeling, and apoptosis.
Chemokines, in particular, are small chemoattractant cytokines involved in inflammation, s leukocyte proliferation and migration, angiogenesis and angiostasis, regulation of hematopoiesis, HIV
infectivity, and stimulation of cytokine secretion. Chemokines generally contain 70-100 amino acids and are subdivided into four subfamilies based on the presence of conserved cysteine-based motifs.
(Callard, R. and Gearing, A. (1994) The Cytokine Facts Book, Academic Press, New York, NY, pp.
181-190, 210-213, 223-227.) to Growth and differentiation factors are secreted proteins which function in intercellular communication. Some factors require oligomerization or association with MPs for activity. Complex interactions among these factors and their receptors trigger intracellular signal transduction pathways that stimulate or inhibit cell division, cell differentiation, cell signaling, and cell motility. Most growth and differentiation factors act on cells in their local environment (paracrine signaling). There is are three broad classes of growth and differentiation factors. The first class includes the large polypeptide growth factors such as epidermal growth factor, fibroblast growth factor, transforming growth factor, insulin-like growth factor, and platelet-derived growth factor.
The second class includes the hematopoietic growth factors such as the colony stimulating factors (CSFs).
Hematopoietic growth factors stimulate the proliferation and differentiation of blood cells such as B-20 lymphocytes, T-lymphocytes, erythrocytes, platelets, eosinophils, basophils, neutrophils, macrophages, and their stem cell precursors. The third class includes small peptide factors such as bombesin, vasopressin, oxytocin, endothelin, transferrin, angiotensin II, vasoactive intestinal peptide, and bradykinin which function as hormones to regulate cellular functions other than proliferation.
Growth and differentiation factors play critical roles in neoplastic transformation of cells in 2s vitro and in tumor progression in vivo. Inappropriate expression of growth factors by tumor cells may contribute to vascularization and metastasis of tumors. During hematopoiesis, growth factor misregulation can result in anemias, leukemias, and lymphomas. Certain growth factors such as interferon are cytotoxic to tumor cells both in vivo and in vitro. Moreover, some growth factors and growth factor receptors are related both structurally and functionally to oncoproteins. In addition, 3o growth factors affect transcriptional regulation of both proto-oncogenes and oncosuppressor genes.
(Reviewed in Pimentel, E. (1994) Handbook of Growth Factors, CRC Press, Ann Arbor, MI, pp. 1-9.) Proteolytic enzymes or proteases either activate or deactivate proteins by hydrolyzing peptide bonds. Proteases are found in the cytosol, in membrane-bound compartments, and in the extracellular space. The major families are the zinc, serine, cysteine, thiol, and carboxyl proteases.
3s Ion channels, ion pumps, and transport proteins mediate the transport of molecules across cellular membranes. Transport can occur by a passive, concentration-dependent mechanism or can be linked to an energy source such as ATP hydrolysis. Symporters and antiporters transport ions and small molecules such as amino acids, glucose, and drugs. Symporters transport molecules and ions unidirectionally, and antiporters transport molecules and ions bidirectionally. Transporter superfamilies include facilitative transporters and active ATP-binding cassette transporters which are s involved in multiple-drug resistance and the targeting of antigenic peptides to MHC Class I
molecules. These transporters bind to a specific ion or other molecule and undergo a conformational change in order to transfer the ion or molecule across the membrane. (Reviewed in Alberts, B. et al.
(1994) Molecular Biology of The Cell, Garland Publishing, New York, NY, pp.
523-546.) Ion channels are formed by transmembrane proteins which create a lined passageway across to the membrane through which water and ions, such as Na+, K+, Ca2+, and Cl-, enter and exit the cell.
For example, chloride channels are involved in the regulation of the membrane electric potential as well as absorption and secretion of ions across the membrane. Chloride channels also regulate the internal pH of membrane-bound organelles.
Ion pumps are ATPases which actively maintain membrane gradients. Ion pumps are is classified as P, V, or F according to their structure and function. All have one or more binding sites for ATP in their cytosolic domains. The P-class ion pumps include Ca2+ ATPase and Na'/K+ ATPase and function in transporting H+, Na+, K+, and Caz+ ions. P-class pumps consist of two a and two [3 transmembrane subunits. The V- and F-class ion pumps have similar structures but transport only H+.
F class H+ pumps mediate transport across the membranes of mitochondria and chloroplasts, while V-2 o class H+ pumps regulate acidity inside lysosomes, endosomes, and plant vacuoles.
A family of structurally related intrinsic membrane proteins known as facilitative glucose transporters catalyze the movement of glucose and other selected sugars across the plasma membrane.
The proteins in this family contain a highly conserved, large transmembrane domain comprised of 12 a-helices, and several weakly conserved, cytoplasmic and exoplasmic domains.
(Pessin, J. E., and 2s Bell, G.I. (1992) Annu. Rev. Physiol. 54:911-930.) Amino acid transport is mediated by Na+ dependent amino acid transporters.
These transporters are involved in gastrointestinal and renal uptake of dietary and cellular amino acids and in neuronal reuptake of neurotransmitters. Transport of cationic amino acids is mediated by the system y+ family and the cationic amino acid transporter (CAT) family. Members of the CAT family 3o share a high degree of sequence homology, and each contains 12-14 putative transmembrane domains. (Ito, K. and Groudine, M. (1997) J. Biol. Chem. 272:26780-26786.) Hormones are secreted molecules that travel through the circulation and bind to specific receptors on the surface of, or within, target cells. Although they have diverse biochemical compositions and mechanisms of action, hormones can be grouped into two categories. One category 35 includes small lipophilic hormones that diffuse through the plasma membrane of target cells, bind to cytosolic or nuclear receptors, and form a complex that alters gene expression. Examples of these molecules include retinoic acid, thyroxine, and the cholesterol-derived steroid hormones such as progesterone, estrogen, testosterone, cortisol, and aldosterone. The second category includes hydrophilic hormones that function by binding to cell surface receptors that transduce signals across the plasma membrane. Examples of such hormones include amino acid derivatives such as s catecholamines and peptide hormones such as glucagon, insulin, gastrin, secretin, cholecystokinin, adrenocorticotropic hormone, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, and vasopressin. (See, for example, Lodish et al. (1995) Molecular Cell BioloQV, Scientific American Books Inc., New York, NY, pp. 856-864.) Neuropeptides and vasomediators (NP/VM) comprise a large family of endogenous signaling to molecules. Included in this family are neuropeptides and neuropeptide hormones such as bombesin, neuropeptide Y, neurotensin, neuromedin N, melanocortins, opioids, galanin, somatostatin, tachykinins, urotensin II and related peptides involved in smooth muscle stimulation, vasopressin, vasoactive intestinal peptide, and circulatory system-borne signaling molecules such as angiotensin, complement, calcitonin, endothelins, formyl-methionyl peptides, glucagon, cholecystokinin and 15 gastrin. NP/VMs can transduce signals directly, modulate the activity or release of other neurotransmitters and hormones, and act as catalytic enzymes in cascades. The effects of NP/VMs range from extremely brief to long-lasting. (Reviewed in Martin, C. R. et al.
(1985) Endocrine Physiology, Oxford University Press, New York, NY, pp. 57-62.) The discovery of new secretory molecules satisfies a need in the art by providing new 2o compositions which are useful in the diagnosis, study, prevention, and treatment of diseases associated with cell signaling.
SUMMARY OF THE INVENTION
The present invention relates to nucleic acid sequences comprising human polynucleotides 2s encoding secretory polypeptides that contain signal peptides and/or transmembrane domains. These human polynucleotides (sptm) as presented in the Sequence Listing uniquely identify genes encoding structural, functional, and regulatory polypeptides (SPTM) involved in cell signaling.
The invention provides an isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting 30 of SEQ )D NO:1-26; b) a naturally occurring polynucleotide sequence having at least 90°1o sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b);
and e) an RNA equivalent of a) through d). In one alternative, the polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26.
In another 35 alternative, the polynucleotide comprises at least 60 contiguous nucleotides of a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26; b) a naturally occurring polynucleotide sequence having at least 90%
sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The invention further provides a composition for s the detection of expression of secretory polynucleotides comprising at least one isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26;
b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ >D NO:1-26; c) a polynucleotide sequence to complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d); and a detectable label.
The invention also provides a method for detecting a target polynucleotide in a sample, said target polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ )D NO:1-26;
b) a naturally 15 occurnng polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the 2o sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof. In one alternative, the probe comprises at least 30 contiguous nucleotides. In another alternative, the probe comprises at least 60 contiguous nucleotides.
z 5 The invention further provides a recombinant polynucleotide comprising a promoter sequence operably linked to an isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26; b) a naturally occurring polynucleotide sequence having at least 90%
sequence identity to a polynucleotide sequence selected from the group consisting of SEQ )D NO:1-26;
c) a polynucleotide 3o sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA
equivalent of a) through d). In one alternative, the invention provides a cell transformed with the recombinant polynucleotide. In another alternative, the invention provides a transgenic organism comprising the recombinant polynucleotide. In a further alternative, the invention provides a method for producing a secretory polypeptide, the method comprising a) culturing a cell under conditions 35 suitable for expression of the secretory polypeptide, wherein said cell is transformed with the recombinant polynucleotide, and b) recovering the secretory polypeptide so expressed.

The invention also provides a purified secretory polypeptide (SPTM) encoded by at least one polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ 1D
NO:1-26. Additionally, the invention provides an isolated antibody which specifically binds to the secretory polypeptide. The invention further provides a method of identifying a test compound which specifically binds to the secretory polypeptide, the method comprising the steps of a) providing a test compound; b) combining the secretory polypeptide with the test compound for a sufficient time and under suitable conditions for binding; and c) detecting binding of the secretory polypeptide to the test compound, thereby identifying the test compound which specifically binds the secretory polypeptide.
The invention further provides a microarray wherein at least one element of the microarray is to an isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ )D NO:1-26; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ )D NO:1-26; c) a polynucleotide sequence complementary to a); d) is a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The invention also provides a method for generating a transcript image of a sample which contains polynucleotides. The method comprises a) labeling the polynucleotides of the sample, b) contacting the elements of the microarray with the labeled polynucleotides of the sample under conditions suitable for the formation of a hybridization complex, and c) quantifying the expression of the 2o polynucleotides in the sample.
Additionally, the invention provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ 1D NO:1-26; b) a naturally occurnng polynucleotide sequence 25 having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ >D NO:1-26; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The method comprises a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.
3o The invention further provides a method for detecting a target polynucleotide in a sample for toxicity testing of a compound, said target polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ 1D NO:1-26; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26; c) a 35 polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b);
and e) an RNA equivalent of a) through d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide, b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof, and c) comparing the presence, absence or amount of said target polynucleotide in a first biological sample and a second biological sample, wherein said first biological sample has been contacted with said compound, and said second sample is a control, whereby a change in presence, absence or amount of said target polynucleotide in said first sample, as compared with said second sample, is indicative of toxic response to said compound.
to DESCRIPTION OF THE TABLES
Table 1 shows the sequence identification numbers (SEQ ID NOa) and template identification numbers (template IDs) corresponding to the polynucleotides of the present invention, along with their GenBank hits (GI Numbers), probability scores, and functional annotations is corresponding to the GenBank hits.
Table 2 shows the sequence identification numbers (SEQ >D NOa) and template identification numbers (template IDs) corresponding to the polynucleotides of the present invention, along with polynucleotide segments of each template sequence as defined by the indicated "start" and "stop" nucleotide positions. The reading frames of the polynucleotide segments are shown, and the 2 o polypeptides encoded by the polynucleotide segments constitute either signal peptide (SP) or transmembrane (TM) domains, as indicated.
Table 3 shows the sequence identification numbers (SEQ )D NOa) and template identification numbers (template IDs) corresponding to the polynucleotides of the present invention, along with component sequence identification numbers (component IDs) corresponding to each 2 s template. The component sequences, which were used to assemble the template sequences, are defined by the indicated "start" and "stop" nucleotide positions along each template.
Table 4 summarizes the bioinformatics tools which are useful for analysis of the polynucleotides of the present invention. The first column of Table 4 lists analytical tools, programs, and algorithms, the second column provides brief descriptions thereof, the third column presents 3 o appropriate references, all of which are incorporated by reference herein in their entirety, and the fourth column presents, where applicable, the scores, probability values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score, the greater the homology between two sequences).

Before the nucleic acid sequences and methods are presented, it is to be understood that this invention is not limited to the particular machines, methods, and materials described. Although particular embodiments are described, machines, methods, and materials similar or equivalent to these embodiments may be used to practice the invention. The preferred machines, methods, and materials set forth are not intended to limit the scope of the invention which is limited only by the s appended claims.
The singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. All technical and scientific terms have the meanings commonly understood by one of ordinary skill in the art. All publications are incorporated by reference for the purpose of describing and disclosing the cell lines, vectors, and methodologies which are presented and which to might be used in connection with the invention. Nothing in the specification is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.
Definitions As used herein, the lower case "sptm" refers to a nucleic acid sequence, while the upper case 15 "SPTM" refers to an amino acid sequence encoded by sptm. A "full-length"
sptm refers to a nucleic acid sequence containing the entire coding region of a gene endogenously expressed in human tissue.
"Adjuvants" are materials such as Freund's adjuvant, mineral gels (aluminum hydroxide), and' surface active substances (lysolecithin, pluronic polyols, polyanions, peptides" oil emulsions, keyhole limpet hemocyanin, and dinitrophenol) which may be administered to increase a host's 2 o immunological response.
"Allele" refers to an alternative form of a nucleic acid sequence. Alleles result from a "mutation," a change or an alternative reading of the genetic code. Any given gene may have none, one, or many allelic forms. Mutations which give rise to alleles include deletions, additions, or substitutions of nucleotides. Each of these changes may occur alone, or in combination with the 25 others, one or more times in a given nucleic acid sequence. The present invention encompasses allelic sptm.
"Amino acid sequence" refers to a peptide, a polypeptide, or a protein of either natural or synthetic origin. The amino acid sequence is not limited to the complete, endogenous amino acid sequence and may be a fragment, epitope, variant, or derivative of a protein expressed by a nucleic 3 o acid sequence.
"Amplification" refers to the production of additional copies of a sequence and is carried out using polymerase chain reaction (PCR) technologies well known in the art.
"Antibody" refers to intact molecules as well as to fragments thereof, such as Fab, F(ab')2, and Fv fragments, which are capable of binding the epitopic determinant.
Antibodies that bind SPTM
35 polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or peptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and can be conjugated to a carrier protein if desired. Commonly used Garners that are chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet hemocyanin (KLH).
The coupled peptide is then used to immunize the animal.
"Antisense sequence" refers to a sequence capable of specifically hybridizing to a target sequence. The antisense sequence may include DNA, RNA, or any nucleic acid mimic or analog such as peptide nucleic acid (PNA); oligonucleotides having modified backbone linkages such as phosphorothioates, methylphosphonates, or benzylphosphonates; oligonucleotides having modified sugar groups such as 2'-methoxyethyl sugars or 2'-methoxyethoxy sugars; or oligonucleotides having to modified bases such as 5-methyl cytosine, 2'-deoxyuracil, or 7-deaza-2'-deoxyguanosine.
"Antisense sequence" refers to a sequence capable of specifically hybridizing to a target sequence. The antisense sequence can be DNA, RNA, or any nucleic acid mimic or analog.
"Antisense technology" refers to any technology which relies on the specific hybridization of an antisense sequence to a target sequence.
A "bin" is a portion of computer memory space used by a computer program for storage of data, and bounded in such a manner that data stored in a bin may be retrieved by the program.
"Biologically active" refers to an amino acid sequence having a structural, regulatory, or biochemical function of a naturally occurring amino acid sequence.
"Clone joining" is a process for combining gene bins based upon the bins' containing 2 o sequence information from the same clone. The sequences may assemble into a primary gene transcript as well as one or more splice variants.
"Complementary" describes the relationship between two single-stranded nucleic acid sequences that anneal by base-pairing (5'-A-G-T-3' pairs with its complement 3'-T-C-A-5').
A "component sequence" is a nucleic acid sequence selected by a computer program such as PHRED and used to assemble a consensus or template sequence from one or more component sequences.
A "consensus sequence" or "template sequence" is a nucleic acid sequence which has been assembled from overlapping sequences, using a computer program for fragment assembly such as the GELVIEW fragment assembly system (Genetics Computer Group (GCG), Madison WI) or using a 3o relational database management system (RDMS).
"Conservative amino acid substitutions" are those substitutions that, when made, least interfere with the properties of the original protein, i.e., the structure and especially the function of the protein is conserved and not significantly changed by such substitutions.
The table below shows amino acids which may be substituted for an original amino acid in a protein and which are regarded as conservative substitutions.

Original Residue Conservative Substitution Ala Gly, Ser Arg His, Lys Asn Asp, Gln, His Asp Asn, Glu Cys Ala, Ser Gln Asn, Glu, His Glu Asp, Gln, His Gly Ala to His Asn, Arg, Gln, Glu Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu Met Leu, Ile Phe His, Met, Leu, Trp, Tyr Ser Cys, Thr Thr Ser, Val Trp Phe, Tyr Tyr His, Phe, Trp 2o Val Ile, Leu, Thr Conservative substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain.
"Deletion" refers to a change in either a nucleic or amino acid sequence in which at least one nucleotide or amino acid residue, respectively, is absent.
"Derivative" refers to the chemical modification of a nucleic acid sequence, such as by replacement of hydrogen by an alkyl, acyl, amino, hydroxyl, or other group.
3 o The terms "element" and "array element" refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray.
"E-value" refers to the statistical probability that a match between two sequences occurred by chance.
A "fragment" is a unique portion of sptm or SPTM which is identical in sequence to but shorter in length than the parent sequence. A fragment may comprise up to the entire length of the defined sequence, minus one nucleotidelamino acid residue. For example, a fragment may comprise from 10 to 1000 contiguous amino acid residues or nucleotides. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other purposes, may be at least 5, 10, 15, 16, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500 contiguous amino acid residues or nucleotides in length.
4o Fragments may be preferentially selected from certain regions of a molecule. For example, a polypeptide fragment may comprise a certain length of contiguous amino acids selected from the first 250 or 500 amino acids (or first 25% or 50%) of a polypeptide as shown in a certain defined sequence. Clearly these lengths are exemplary, and any length that is supported by the specification, including the Sequence Listing and the figures, may be encompassed by the present embodiments.
A fragment of sptm comprises a region of unique polynucleotide sequence that specifically identifies sptm, for example, as distinct from any other sequence in the same genome. A fragment of sptm is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish sptm from related polynucleotide sequences. The precise length of a fragment of sptm and the region of sptm to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.
A fragment of SPTM is encoded by a fragment of sptm. A fragment of SPTM
comprises a 1o region of unique amino acid sequence that specifically identifies SPTM. For example, a fragment of SPTM is useful as an immunogenic peptide for the development of antibodies that specifically recognize SPTM. The precise length of a fragment of SPTM and the region of SPTM to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.
A "full length" nucleotide sequence is one containing at least a start site for translation to a protein sequence, followed by an open reading frame and a stop site, and encoding a "full length"
polypeptide.
"Hit" refers to a sequence whose annotation will be used to describe a given template.
Criteria for selecting the top hit are as follows: if the template has one or more exact nucleic acid 2 o matches, the top hit is the exact match with highest percent identity. If the template has no exact matches but has significant protein hits, the top hit is the protein hit with the lowest E-value. If the template has no significant protein hits, but does have significant non-exact nucleotide hits, the top hit is the nucleotide hit with the lowest E-value.
"Homology" refers to sequence similarity either between a reference nucleic acid sequence 2 5 and at least a fragment of an sptm or between a reference amino acid sequence and a fragment of an SPTM.
"Hybridization" refers to the process by which a strand of nucleotides anneals with a complementary strand through base pairing. Specific hybridization is an indication that two nucleic acid sequences share a high degree of identity. Specific hybridization complexes form under defined 3 o annealing conditions, and remain hybridized after the "washing" step. The defined hybridization conditions include the annealing conditions and the washing step(s), the latter of which is particularly important in determining the stringency of the hybridization process, with more stringent conditions allowing less non-specific binding, i.e., binding between pairs of nucleic acid probes that are not perfectly matched. Permissive conditions for annealing of nucleic acid sequences are routinely 35 determinable and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency.

Generally, stringency of hybridization is expressed with reference to the temperature under which the wash step is carried out. Generally, such wash temperatures are selected to be about 5°C to 20°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The T", is the temperature (under defined ionic strength and pH) at which 50% of the target s sequence hybridizes to a perfectly matched probe. An equation for calculating Tm and conditions for nucleic acid hybridization is well known and can be found in Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2°° ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY;
specifically see volume 2, chapter 9.
High stringency conditions for hybridization between polynucleotides of the present to invention include wash conditions of 68°C in the presence of about 0.2 x SSC and about 0.1% SDS, for 1 hour. Alternatively, temperatures of about 65°C, 60°C, or 55°C may be used. SSC
concentration may be varied from about 0.2 to 2 x SSC, with SDS being present at about 0.1 %.
Typically, blocking reagents are used to block non-specific hybridization.
Such blocking reagents include, for instance, denatured salmon sperm DNA at about 100-200 pg/ml.
Useful variations on 15 these conditions will be readily apparent to those skilled in the art.
Hybridization, particularly under high stringency conditions, may be suggestive of evolutionary similarity between the nucleotides.
Such similarity is strongly indicative of a similar role for the nucleotides and their resultant proteins.
Other parameters, such as temperature, salt concentration, and detergent concentration may be varied to achieve the desired stringency. Denaturants, such as formanude at a concentration of 2o about 35-50% v/v, may also be used under particular circumstances, such as RNA:DNA
hybridizations. Appropriate hybridization conditions are routinely determinable by one of ordinary skill in the art.
"Immunogenic" describes the potential for a natural, recombinant, or synthetic peptide, epitope, polypeptide, or protein to induce antibody production in appropriate animals, cells, or cell 25 lines.
"Insertion" or "addition" refers to a change in either a nucleic or amino acid sequence in which at least one nucleotide or residue, respectively, is added to the sequence.
"Labeling" refers to the covalent or noncovalent joining of a polynucleotide, polypeptide, or antibody with a reporter molecule capable of producing a detectable or measurable signal.
30 "Microarray" is any arrangement of nucleic acids, amino acids, antibodies, etc., on a substrate. The substrate may be a solid support such as beads, glass, paper, nitrocellulose, nylon, or an appropriate membrane.
"Linkers" are short stretches of nucleotide sequence which may be added to a vector or an sptm to create restriction endonuclease sites to facilitate cloning.
"Polylinkers" are engineered to 35 incorporate multiple restriction enzyme sites and to provide for the use of enzymes which leave 5' or 3' overhangs (e.g., BamHI, EcoRI, and HindII>] and those which provide blunt ends (e.g., EcoRV, SnaBI, and Stun.
"Naturally occurring" refers to an endogenous polynucleotide or polypeptide that may be isolated from viruses or prokaryotic or eukaryotic cells.
"Nucleic acid sequence" refers to the specific order of nucleotides joined by phosphodiester bonds in a linear, polymeric arrangement. Depending on the number of nucleotides, the nucleic acid sequence can be considered an oligomer, oligonucleotide, or polynucleotide.
The nucleic acid can be DNA, RNA, or any nucleic acid analog, such as PNA, may be of genomic or synthetic origin, may be either double-stranded or single-stranded, and can represent either the sense or antisense i o (complementary) strand.
"Oligomer" refers to a nucleic acid sequence of at least about 6 nucleotides and as many as about 60 nucleotides, preferably about 15 to 40 nucleotides, and most preferably between about 20 and 30 nucleotides, that may be used in hybridization or amplification technologies. Oligomers may be used as, e.g., primers for PCR, and are usually chemically synthesized.
"Operably linked" refers to the situation in which a first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences may be in close proxinuty or contiguous and, where necessary to join two protein coding regions, in the same reading frame.
"Peptide nucleic acid" (PNA) refers to a DNA mimic in which nucleotide bases are attached to a pseudopeptide backbone to increase stability. PNAs, also designated antigene agents, can prevent gene expression by targeting complementary messenger RNA.
The phrases "percent identity" and "% identity", as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences.
Percent identity between polynucleotide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN
version 3.12e 3o sequence alignment program. This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison WI). CLUSTAL V is described in Higgins, D.G. and Sharp, P.M. (1989) CABIOS 5:151-153 and in Higgins, D.G. et al. (1992) CABIOS 8:189-191. For pairwise alignments of polynucleotide sequences, the default parameters are set as follows: Ktuple=2, gap penalty=5, window=4, and "diagonals saved"=4.
The "weighted"
residue weight table is selected as the default. Percent identity is reported by CLUSTAL V as the "percent similarity" between aligned polynucleotide sequence pairs.

Alternatively, a suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S.F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, MD, and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes various sequence analysis programs including "blastn," that is used to determine alignment between a known polynucleotide sequence and other sequences on a variety of databases. Also available is a tool called "BLAST 2 Sequences" that is used for direct pairwise comparison of two nucleotide sequences.
"BLAST 2 Sequences" can be accessed and used interactively at to http:/lwww.ncbi.nlm.nih.govlgorf/b12/. The "BLAST 2 Sequences" tool can be used for both blastn and blastp (discussed below). BLAST programs are commonly used with gap and other parameters set to default settings. For example, to compare two nucleotide sequences, one may use blastn with the "BLAST 2 Sequences" tool Version 2Ø9 (May-07-1999) set at default parameters. Such default parameters may be, for example:
Matrix: BLOSUM62 Reward for match: 1 Penalty for mismatch: -2 Open Gap: S and Extension Gap: 2 penalties Gap x drop-off.' SO
z o Expect: 70 Word Size: J I
Filter: on Percent identity may be measured over the length of an entire defined sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in figures or Sequence Listings, may be used to describe a length over which percentage identity may be measured.
3 o Nucleic acid sequences that do not show a high degree of identity may nevertheless encode similar amino acid sequences due to the degeneracy of the genetic code. It is understood that changes in nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid sequences that all encode substantially the same protein.
The phrases "percent identity" and "°!o identity", as applied to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment methods take into account conservative amino acid substitutions.
Such conservative substitutions, explained in more detail above, generally preserve the hydrophobicity and acidity of the substituted residue, thus preserving the structure (and therefore function) of the folded polypeptide.
Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN
version 3.12e sequence alignment program (described and referenced above). For pairwise alignments of polypeptide sequences using CLUSTAL V, the default parameters are set as follows: Ktuple=1, gap penalty=3, window=5, and "diagonals saved"=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide alignments, the percent identity is reported by 1o CLUSTAL V as the "percent similarity" between aligned polypeptide sequence pairs.
Alternatively the NCBI BLAST software suite may be used. For example, for a pairwise comparison of two polypeptide sequences, one may use the "BLAST 2 Sequences"
tool Version 2Ø9 (May-07-1999) with blastp set at default parameters. Such default parameters may be, for example:
Matrix: BLOSUM62 Open Gap: 1l and Extension Gap: l penalty Cap x drop-off.' S0 Expect: 10 Word Size: 3 Filter: on 2o Percent identity may be measured over the length of an entire defined polypeptide sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in figures or Sequence Listings, may be used to describe a length over which percentage identity may be measured.
"Post-translational modification" of an SPTM may involve lipidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur synthetically or biochemically. Biochemical modifications will 3 o vary by cell type depending on the enzymatic milieu and the SPTM.
"Probe" refers to sptm or fragments thereof, which are used to detect identical, allelic or related nucleic acid sequences. Probes are isolated oligonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, ligands, chemiluminescent agents, and enzymes. "Primers" are short nucleic acids, usually DNA
oligonucleotides, which may be annealed to a target polynucleotide by complementary base-pairing.
The primer may then be extended along the target DNA strand by a DNA
polymerase enzyme.

Primer pairs can be used for amplification (and identification) of a nucleic acid sequence, e.g., by the polymerase chain reaction (PCR).
Probes and primers as used in the present invention typically comprise at least 15 contiguous nucleotides of a known sequence. In order to enhance specificity, longer probes and primers may also be employed, such as probes and primers that comprise at least 20, 30, 40, 50, 60, 70, 80, 90, 100, or at least 150 consecutive nucleotides of the disclosed nucleic acid sequences.
Probes and primers may be considerably longer than these examples, and it is understood that any length supported by the specification, including the figures and Sequence Listing, may be used.
Methods for preparing and using probes and primers are described in the references, for to example Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2"d ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; Ausubel et a1.,1987, Current Protocols in Molecular Biology, Greene Publ. Assoc. & Wiley-Intersciences, New York NY; Innis et al., 1990, PCR Protocols, A
Guide to Methods and Applications, Academic Press, San Diego CA. PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that purpose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge MA).
Oligonucleotides for use as primers are selected using software known in the art for such purpose. For example, OLIGO 4.06 software is useful for the selection of PCR
primer pairs of up to 100 nucleotides each, and for the analysis of oligonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases.
Similar primer 2 o selection programs have incorporated additional features for expanded capabilities. For example, the PrimOU primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas TX) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome-wide scope. The Primer3 primer selection program (available to the public from the Whitehead Institute/MIT Center for 2 s Genome Research, Cambridge MA) allows the user to input a "mispriming library," in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user's specific needs.) The PrimeGen program (available to the public from the UK Human Genome Mapping 3o Project Resource Centre, Cambridge UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences. Hence, this program is useful for identification of both unique and conserved oligonucleotides and polynucleotide fragments. The oligonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization 3 s technologies, for example, as PCR or sequencing primers, microarray elements, or specific probes to identify fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.
"Purified" refers to molecules, either polynucleotides or polypeptides that are isolated or separated from their natural environment and are at least 60% free, preferably at least 75% free, and most preferably at least 90% free from other compounds with which they are naturally associated.
A "recombinant nucleic acid" is a sequence that is not naturally occurnng or has a sequence that is made by an artificial combination of two or more otherwise separated segments of sequence.
This artificial combination is often accomplished by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, e.g., by genetic engineering techniques to such as those described in Sambrook, supra. The term recombinant includes nucleic acids that have been altered solely by addition, substitution, or deletion of a portion of the nucleic acid. Frequently, a recombinant nucleic acid may include a nucleic acid sequence operably linked to a promoter sequence. Such a recombinant nucleic acid may be part of a vector that is used, for example, to transform a cell.
Alternatively, such recombinant nucleic acids may be part of a viral vector, e.g., based on a vaccinia virus, that could be use to vaccinate a mammal wherein the recombinant nucleic acid is expressed, inducing a protective immunological response in the mammal.
"Regulatory element" refers to a nucleic acid sequence from nontranslated regions of a gene, and includes enhancers, promoters, introns, and 3' untranslated regions, which interact with host 2 o proteins to carry out or regulate transcription or translation.
"Reporter" molecules are chemical or biochemical moieties used for labeling a nucleic acid, an amino acid, or an antibody. They include radionuclides; enzymes;
fluorescent, chemiluminescent, or chromogenic agents; substrates; cofactors; inhibitors; magnetic particles;
and other moieties known in the art.
An "RNA equivalent," in reference to a DNA sequence, is composed of the same linear sequence of nucleotides as the reference DNA sequence with the exception that all occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.
"Sample" is used in its broadest sense. Samples may contain nucleic or amino acids, 3o antibodies, or other materials, and may be derived from any source (e.g., bodily fluids including, but not limited to, saliva, blood, and urine; chromosome(s), organelles, or membranes isolated from a cell; genomic DNA, RNA, or cDNA in solution or bound to a substrate; and cleared cells or tissues or blots or imprints from such cells or tissues).
"Specific binding" or "specifically binding" refers to the interaction between a protein or peptide and its agonist, antibody, antagonist, or other binding partner. The interaction is dependent upon the presence of a particular structure of the protein, e.g., the antigenic determinant or epitope, recognized by the binding molecule. For example, if an antibody is specific for epitope "A," the presence of a polypeptide containing epitope A, or the presence of free unlabeled A, in a reaction containing free labeled A and the antibody will reduce the amount of labeled A
that binds to the antibody.
"Substitution" refers to the replacement of at least one nucleotide or amino acid by a different nucleotide or anuno acid.
"Substrate" refers to any suitable rigid or semi-rigid support including, e.g., membranes, filters, chips, slides, wafers, fibers, magnetic or nonmagnetic beads, gels, tubing, plates, polymers, microparticles or capillaries. The substrate can have a variety of surface forms, such as wells, Zo trenches, pins, channels and pores, to which polynucleotides or polypeptides are bound.
A "transcript image" refers to the collective pattern of gene expression by a particular tissue or cell type under given conditions at a given time.
"Transformation" refers to a process by which exogenous DNA enters a recipient cell.
Transformation may occur under natural or artificial conditions using various methods well known in i5 the art. Transformation may rely on any known method for the insertion of foreign nucleic acid sequences into a prokaryotic or eukaryotic host cell. The method is selected based on the host cell being transformed.
"Transformants" include stably transformed cells in which the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome, as well zo as cells which transiently express inserted DNA or RNA.
A "transgenic organism," as used herein, is any organism, including but not limited to animals and plants, in which one or more of the cells of the organism contains heterologous nucleic acid introduced by way of human intervention, such as by transgenic techniques well known in the art.
The nucleic acid is introduced into the cell, directly or indirectly by introduction into a precursor of 25 the cell, by way of deliberate genetic manipulation, such as by microinjection or by infection with a recombinant virus. The term genetic manipulation does not include classical cross-breeding, or in vitro fertilization, but rather is directed to the introduction of a recombinant DNA molecule. The transgenic organisms contemplated in accordance with the present invention include bacteria, cyanobacteria, fungi, and plants and animals. The isolated DNA of the present invention can be s o introduced into the host by methods known in the art, for example infection, transfection, transformation or transconjugation. Techniques for transferring the DNA of the present invention into such organisms are widely known and provided in references such as Sambrook et al. (1989), supra.
A "variant" of a particular nucleic acid sequence is defined as a nucleic acid sequence having 35 at least 25% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the "BLAST 2 Sequences" tool Version 2Ø9 (May-07-1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 30%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or even at least 98% or greater sequence identity over a certain defined length. The variant may result in "conservative"
amino acid changes which do not affect structural and/or chemical properties.
A variant may be described as, for example, an "allelic" (as defined above), "splice,"
"species," or "polymorphic"
variant. A splice variant may have significant identity to a reference molecule, but will generally have a greater or lesser number of polynucleotides due to alternate splicing of exons during mRNA
processing. The corresponding polypeptide may possess additional functional domains or lack domains that are present in the reference molecule. Species variants are polynucleotide sequences to that vary from one species to another. The resulting polypeptides generally will have significant amino acid identity relative to each other. A polymorphic variant is a variation in the polynucleotide sequence of a particular gene between individuals of a given species.
Polymorphic variants also may encompass "single nucleotide polymorphisms" (SNPs) in which the polynucleotide sequence varies by one base. The presence of SNPs may be indicative of, for example, a certain population, a disease is state, or a propensity for a disease state.
In an alternative, variants of the polynucleotides of the present invention may be generated through recombinant methods. One possible method is a DNA shuffling technique such as MOLECULARBREEDING (Maxygen Inc., Santa Clara CA; described in U.S. Patent Number 5,837,458; Chang, C.-C. et al. (1999) Nat. Biotechnol. 17:793-797; Christians, F.C. et al. (1999) Nat.
2o Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol.
14:315-319) to alter or improve the biological properties of SPTM, such as its biological or enzymatic activity or its ability to bind to other molecules or compounds. DNA shuffling is a process by which a library of gene variants is produced using PCR-mediated recombination of gene fragments. The library is then subjected to selection or screening procedures that identify those gene variants with the desired 25 properties. These preferred variants may then be pooled and further subjected to recursive rounds of DNA shuffling and selectionlscreening. Thus, genetic diversity is created through "artificial"
breeding and rapid molecular evolution. For example, fragments of a single gene containing random point mutations may be recombined, screened, and then reshuffled until the desired properties are optimized. Alternatively, fragments of a given gene may be recombined with fragments of 3 o homologous genes in the same gene fanuly, either from the same or different species, thereby maximizing the genetic diversity of multiple naturally occurring genes in a directed and controllable manner.
A "variant" of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of 35 the polypeptide sequences using blastp with the "BLAST 2 Sequences" tool Version 2Ø9 (May-07-1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% or greater sequence identity over a certain defined length of one of the polypeptides.
THE INVENTION
In a particular embodiment, cDNA sequences derived from human tissues and cell lines were aligned based on nucleotide sequence identity and assembled into "consensus"
or "template"
sequences which are designated by the template identification numbers (template IDs) in column 2 of Table 1. The sequence identification numbers (SEQ ID NOa) corresponding to the template IDs are shown in column 1. The template sequences have similarity to GenBank sequences, or "hits," as to designated by the GI Numbers in column 3. The statistical probability of each GenBank hit is indicated by a probability score in column 4, and the functional annotation corresponding to each GenBank hit is listed in column 5.
Segments of each template sequences are defined by the "start" and "stop"
nucleotide positions listed in columns 3 and 4 of Table 2. These segments, when translated in the reading frames i5 indicated in column 5, have similarity to signal peptide (SP) or transmembrane (TM) domain consensus sequences, as indicated in column 6.
The invention incorporates the nucleic acid sequences of these templates as disclosed in the Sequence Listing and the use of these sequences in the diagnosis and treatment of disease states characterized by defects in cell signaling. The invention further utilizes these sequences in 2o hybridization and amplification technologies, and in particular, in technologies which assess gene expression patterns correlated with specific cells or tissues and their responses in vivo or in vitro to pharmaceutical agents, toxins, and other treatments. In this manner, the sequences of the present invention are used to develop a transcript image for a particular cell or tissue.
z s Derivation of Nucleic Acid Sequences cDNA was isolated from libraries constructed using RNA derived from normal and diseased human tissues and cell lines. The human tissues and cell lines used for cDNA
library construction were selected from a broad range of sources to provide a diverse population of cDNAs representative of gene transcription throughout the human body. Descriptions of the human tissues and cell lines 3 o used for cDNA library construction are provided in the LIFESEQ database (Incyte Genomics, Inc.
(Incyte), Palo Alto CA). Human tissues were broadly selected from, for example, cardiovascular, dermatologic, endocrine, gastrointestinal, hematopoietic/immune system, musculoskeletal, neural, reproductive, and urologic sources.
Cell lines used for cDNA library construction were derived from, for example, leukemic 35 cells, teratocarcinomas, neuroepitheliomas, cervical carcinoma, lung fibroblasts, and endothelial cells.
Such cell lines include, for example, THP-1, Jurkat, HUVEC, hNT2, WI38, HeLa, and other cell lines commonly used and available from public depositories (American Type Culture Collection, Manassas VA). Prior to mRNA isolation, cell lines were untreated, treated with a pharmaceutical agent such as 5 =aza-2'-deoxycytidine, treated with an activating agent such as lipopolysaccharide in the case of leukocytic cell lines, or, in the case of endothelial cell lines, subjected to shear stress.
Sepuencin~ of the cDNAs Methods for DNA sequencing are well known in the art. Conventional enzymatic methods employ the Klenow fragment of DNA polymerase I, SEQUENASE DNA polymerase (U.S.
Biochemical Corporation, Cleveland OH), Taq polymerase (PE Biosystems, Foster City CA), to thermostable T7 polymerase (Amersham Pharmacia Biotech, Inc. (Amersham Pharmacia Biotech), Piscataway NJ), or combinations of polymerases and proofreading exonucleases such as those found in the ELONGASE amplification system (Life Technologies Inc. (Life Technologies), Gaithersburg MD), to extend the nucleic acid sequence from an oligonucleotide primer annealed to the DNA
template of interest. Methods have been developed for the use of both single-stranded and double-ts stranded templates. Chain termination reaction products may be electrophoresed on urea-polyacrylamide gels and detected either by autoradiography (for radioisotope-labeled nucleotides) or by fluorescence (for fluorophore-labeled nucleotides). Automated methods for mechanized reaction preparation, sequencing, and analysis using fluorescence detection methods have been developed.
Machines used to prepare cDNAs for sequencing can include the MICROLAB 2200 liquid transfer 2 o system (Hamilton Company (Hamilton), Reno NV), Pettier thermal cycler (PTC200; MJ Research, Inc. (MJ Research), Watertown MA), and ABI CATALYST 800 thermal cycler (PE
Biosystems).
Sequencing can be carried out using, for example, the ABI 373 or 377 (PE
Biosystems) or MEGABACE 1000 (Molecular Dynamics, Inc. (Molecular Dynamics), Sunnyvale CA) DNA
sequencing systems, or other automated and manual sequencing systems well known in the art.
25 The nucleotide sequences of the Sequence Listing have been prepared by current, state-of the-art, automated methods and, as such, may contain occasional sequencing errors or unidentified nucleotides. Such unidentified nucleotides are designated by an N. These infrequent unidentified bases do not represent a hindrance to practicing the invention for those skilled in the art. Several methods employing standard recombinant techniques may be used to correct errors and complete the 3o missing sequence information. (See, e.g., those described in Ausubel, F.M.
et al. (1997) Short Protocols in Molecular Biolo~y, John Wiley & Sons, New York NY; and Sambrook, J. et al. (1989) Molecular Cloning. A Laboratory Manual, Cold Spring Harbor Press, Plainview NY.) Assembly of cDNA Sequences 35 Human polynucleotide sequences may be assembled using programs or algorithms well known in the art. Sequences to be assembled are related, wholly or in part, and may be derived from a single or many different transcripts. Assembly of the sequences can be performed using such programs as PHRAP (Phils Revised Assembly Program) and the GELVIEW fragment assembly system (GCG), or other methods known in the art.
Alternatively, cDNA sequences are used as "component" sequences that are assembled into s "template" or "consensus" sequences as follows. Sequence chromatograms are processed, verified, and quality scores are obtained using PHRED. Raw sequences are edited using an editing pathway known as Block 1 (See, e.g., the LIFESEQ Assembled User Guide, Incyte Genomics, Palo Alto, CA).
A series of BLAST comparisons is performed and low-information segments and repetitive elements (e.g., dinucleotide repeats, Alu repeats, etc.) are replaced by "n's", or masked, to prevent spurious to matches. Mitochondria) and ribosomal RNA sequences are also removed. The processed sequences are then loaded into a relational database management system (RDMS) which assigns edited sequences to existing templates, if available. When additional sequences are added into the RDMS, a process is initiated which modifies existing templates or creates new templates from works in progress (i.e., nonfinal assembled sequences) containing queued sequences or the sequences 15 themselves. After the new sequences have been assigned to templates, the templates can be merged into bins. If multiple templates exist in one bin, the bin can be split and the templates reannotated.
Once gene bins have been generated based upon sequence alignments, bins are "clone joined"
based upon clone information. Clone joining occurs when the S' sequence of one clone is present in one bin and the 3' sequence from the same clone is present in a different bin, indicating that the two 2o bins should be merged into a single bin. Only bins which share at least two different clones are merged.
A resultant template sequence may contain either a partial or a full length open reading frame, or all or part of a genetic regulatory element. This variation is due in part to the fact that the full length cDNAs of many genes are several hundred, and sometimes several thousand, bases in 25 length. With current technology, cDNAs comprising the coding regions of large genes cannot be cloned because of vector limitations, incomplete reverse transcription of the mRNA, or incomplete "second strand" synthesis. Template sequences may be extended to include additional contiguous sequences derived from the parent RNA transcript using a variety of methods known to those of skill in the art. Extension may thus be used to achieve the full length coding sequence of a gene.
Analysis of the cDNA Sequences The cDNA sequences are analyzed using a variety of programs and algorithms which are well known in the art. (See, e.g., Ausubel, 1997, supra, Chapter 7.7; Meyers, R.A.
(Ed.) (1995) Molecular Biology and Biotechnology, Wiley VCH, New York NY, pp. 856-853; and Table 4.) These analyses comprise both reading frame determinations, e.g., based on triplet codon periodicity for particular organisms (Fickett, J.W. (1982) Nucleic Acids Res. 10:5303-5318); analyses of potential start and stop codons; and homology searches.
Computer programs known to those of skill in the art for performing computer-assisted searches for amino acid and nucleic acid sequence similarity, include, for example, Basic Local s Alignment Search Tool (BLAST; Altschul, S.F. (1993) J. Mol. Evol. 36:290-300; Altschul, S.F. et al.
(1990) J. Mol. Biol. 215:403-410). BLAST is especially useful in determining exact matches and comparing two sequence fragments of arbitrary but equal lengths, whose alignment is locally maximal and for which the alignment score meets or exceeds a threshold or cutoff score set by the user (Karlin, S. et al. ( 1988) Proc. Natl. Acad. Sci. USA 85:841-845). Using an appropriate search io tool (e.g., BLAST or HMM), GenBank, SwissProt, BLOCKS, PFAM and other databases may be searched for sequences containing regions of homology to a query sptm or SPTM
of the present invention.
Other approaches to the identification, assembly, storage, and display of nucleotide and polypeptide sequences are provided in "Relational Database for Storing Biomolecule Information,"
15 U.S.S.N. 08/947,845, filed October 9, 1997; "Project-Based Full-Length Biomolecular Sequence Database," U.S.S.N. 08/811,758, filed March 6, 1997; and "Relational Database and System for Storing Information Relating to Biomolecular Sequences," U.S.S.N. 09/034,807, filed March 4, 1998, all of which are incorporated by reference herein in their entirety.
Protein hierarchies can be assigned to the putative encoded polypeptide based on, e.g., motif, 2o BLAST, or biological analysis. Methods for assigning these hierarchies are described, for example, in "Database System Employing Protein Function Hierarchies for Viewing Biomolecular Sequence Data," U.S.S.N. 08/812,290, filed March 6, 1997, incorporated herein by reference.
Se9uences of Human Secretory Molecules z s The sptm of the present invention may be used for a variety of diagnostic and therapeutic purposes. For example, an sptm may be used to diagnose a particular condition, disease, or disorder associated with cell signaling. Such conditions, diseases, and disorders include, but are not limited to, a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal 3o hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, a cancer of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; an immune system 3s disorder such as such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AmS), Addison's disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irritable bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflanunation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjogren's syndrome, systemic anaphylaxis, to systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma; and a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease, dementia, Parkinson's i5 disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and 2o Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorder of the central nervous system, cerebral palsy, a neuroskeletal disorder, an autonomic nervous system disorder, a cranial nerve disorder, a spinal cord disease, muscular dystrophy and other neuromuscular disorder, a 25 peripheral nervous system disorder, dermatomyositis and polymyositis, inherited, metabolic, endocrine, and toxic myopathy, myasthenia gravis, periodic paralysis, a mental disorder including mood, anxiety, and schizophrenic disorder, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette's disorder. The sptm can be used to detect the presence of, or to quantify the 3 o amount of, an sptm-related polynucleotide in a sample. This information is then compared to information obtained from appropriate reference samples, and a diagnosis is established.
Alternatively, a polynucleotide complementary to a given sptm can inhibit or inactivate a therapeutically relevant gene related to the sptm.

Analysis of sntm Expression Patterns The expression of sptm may be routinely assessed by hybridization-based methods to determine, for example, the tissue-specificity, disease-specificity, or developmental stage-specificity of sptm expression. For example, the level of expression of sptm may be compared among different cell types or tissues, among diseased and normal cell types or tissues, among cell types or tissues at different developmental stages, or among cell types or tissues undergoing various treatments. This type of analysis is useful, for example, to assess the relative levels of sptm expression in fully or partially differentiated cells or tissues, to determine if changes in sptm expression levels are correlated with the development or progression of specific disease states, and to assess the response to of a cell or tissue to a specific therapy, for example, in pharmacological or toxicological studies.
Methods for the analysis of sptm expression are based on hybridization and amplification technologies and include membrane-based procedures such as northern blot analysis, high-throughput procedures that utilize, for example, microarrays, and PCR-based procedures.
Hybridization and Genetic Analysis The sptm, their fragments, or complementary sequences, may be used to identify the presence of and/or to determine the degree of sinvlarity between two (or more) nucleic acid sequences. The sptm may be hybridized to naturally occurnng or recombinant nucleic acid sequences under appropriately selected temperatures and salt concentrations. Hybridization with a probe based on the 2 o nucleic acid sequence of at least one of the sptm allows for the detection of nucleic acid sequences, including genomic sequences, which are identical or related to the sptm of the Sequence Listing.
Probes may be selected from non-conserved or unique regions of at least one of the polynucleotides of SEQ ID NO:1-26 and tested for their ability to identify or amplify the target nucleic acid sequence using standard protocols.
z5 Polynucleotide sequences that are capable of hybridizing, in particular, to those shown in SEQ m NO:1-26 and fragments thereof, can be identified using various conditions of stringency.
(See, e.g., Wahl, G.M. and S.L. Berger (1987) Methods Enzymol. 152:399-407;
Kimmel, A.R. (1987) Methods Enzymol. 152:507-511.) Hybridization conditions are discussed in "Definitions."
A probe for use in Southern or northern hybridization may be derived from a fragment of an 3 o sptm sequence, or its complement, that is up to several hundred nucleotides in length and is either single-stranded or double-stranded. Such probes may be hybridized in solution to biological materials such as plasmids, bacterial, yeast, or human artificial chromosomes, cleared or sectioned tissues, or to artificial substrates containing sptm. Microarrays are particularly suitable for identifying the presence of and detecting the level of expression for multiple genes of interest by examining gene 35 expression correlated with, e.g., various stages of development, treatment with a drug or compound, or disease progression. An array analogous to a dot or slot blot may be used to arrange and link polynucleotides to the surface of a substrate using one or more of the following: mechanical (vacuum), chemical, thermal, or UV bonding procedures. Such an array may contain any number of sptm and may be produced by hand or by using available devices, materials, and machines.
Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., s Brennan, T.M. et al. (1995) U.S. Patent No. 5,474,796; Schena, M. et al.
(1996) Proc. Natl. Acad. Sci.
USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application W0951251 l 16; Shalon, D. et al.
(1995) PCT application W095/35505; Heller, R.A. et al. (1997) Proc. Natl.
Acad. Sci. USA 94:2150 2155; and Heller, M.J. et al. (1997) U.S. Patent No. 5,605,662.) Probes may be labeled by either PCR or enzymatic techniques using a variety of to commercially available reporter molecules. For example, commercial kits are available for radioactive and chemiluminescent labeling (Amersham Pharmacia Biotech) and for alkaline phosphatase labeling (Life Technologies). Alternatively, sptm may be cloned into commercially available vectors for the production of RNA probes. Such probes may be transcribed in the presence of at least one labeled nucleotide (e.g.,'ZP-ATP, Amersham Pharmacia Biotech).
is Additionally the polynucleotides of SEQ )D NO:1-26 or suitable fragments thereof can be used to isolate full length cDNA sequences utilizing hybridization and/or amplification procedures well known in the art, e.g., cDNA library screening, PCR amplification, etc.
The molecular cloning of such full length cDNA sequences may employ the method of cDNA library screening with probes using the hybridization, stringency, washing, and probing strategies described above and in Ausubel, 2o supra, Chapters 3, 5, and 6. These procedures may also be employed with genomic libraries to isolate genomic sequences of sptm in order to analyze, e.g., regulatory elements.
Genetic Mapping Gene identification and mapping are important in the investigation and treatment of almost all z5 conditions, diseases, and disorders. Cancer, cardiovascular disease, Alzheimer's disease, arthritis, diabetes,,and mental illnesses are of particular interest. Each of these conditions is more complex than the single gene defects of sickle cell anemia or cystic fibrosis, with select groups of genes being predictive of predisposition for a particular condition, disease, or disorder.
For example, cardiovascular disease may result from malfunctioning receptor molecules that fail to clear 3 o cholesterol from the bloodstream, and diabetes may result when a particular individual's immune system is activated by an infection and attacks the insulin-producing cells of the pancreas. In some studies, Alzheimer s disease has been linked to a gene on chromosome 21; other studies predict a different gene and location. Mapping of disease genes is a complex and reiterative process and generally proceeds from genetic linkage analysis to physical mapping.
35 As a condition is noted among members of a family, a genetic linkage map traces parts of chromosomes that are inherited in the same pattern as the condition.
Statistics link the inheritance of particular conditions to particular regions of chromosomes, as defined by RFLP
or other markers.
(See, for example, Lander, E. S. and Botstein, D. (1986) Proc. Natl. Acad.
Sci. USA 83:7353-7357.) Occasionally, genetic markers and their locations are known from previous studies. More often, however, the markers are simply stretches of DNA that differ among individuals. Examples of genetic linkage maps can be found in various scientific journals or at the Online Mendelian Inheritance in Man (OMIM) World Wide Web site.
In another embodiment of the invention, sptm sequences may be used to generate hybridization probes useful in chromosomal mapping of naturally occurring genomic sequences.
Either coding or noncoding sequences of sptm may be used, and in some instances, noncoding to sequences may be preferable over coding sequences. For example, conservation of an sptm coding sequence among members of a mufti-gene family may potentially cause undesired cross hybridization during chromosomal mapping. The sequences may be mapped to a particular chromosome, to a specific region of a chromosome, or to artificial chromosome constructions, e.g., human artificial chromosomes (HACs), yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), bacterial P1 constructions, or single chromosome cDNA libraries. (See, e.g., Harrington, J.J.
et al. (1997) Nat. Genet. 15:345-355; Price, C.M. (1993) Blood Rev. 7:127-134;
and Trask, B.J.
(1991) Trends Genet. 7:149-154.) Fluorescent in situ hybridization (FISH) may be correlated with other physical chromosome mapping techniques and genetic map data. (See, e.g., Meyers, supra, pp. 965-968.) Correlation 2o between the location of sptm on a physical chromosomal map and a specific disorder, or a predisposition to a specific disorder, may help define the region of DNA
associated with that disorder. The sptm sequences may also be used to detect polymorphisms that are genetically linked to the inheritance of a particular condition, disease, or disorder.
In situ hybridization of chromosomal preparations and genetic mapping techniques, such as z5 linkage analysis using established chromosomal markers, may be used for extending existing genetic maps. Often the placement of a gene on the chromosome of another mammalian species, such as mouse, may reveal associated markers even if the number or arm of the corresponding human chromosome is not known. These new marker sequences can be mapped to human chromosomes and may provide valuable information to investigators searching for disease genes using positional 3o cloning or other gene discovery techniques. Once a disease or syndrome has been crudely correlated by genetic linkage with a particular genomic region, e.g., ataxia-telangiectasia to l 1q22-23, any sequences mapping to that area may represent associated or regulatory genes for further investigation.
(See, e.g., Gatti, R.A. et al. (1988) Nature 336:577-580.) The nucleotide sequences of the subject invention may also be used to detect differences in chromosomal architecture due to translocation, 35 inversion, etc., among normal, carrier, or affected individuals.

Once a disease-associated gene is mapped to a chromosomal region, the gene must be cloned in order to identify mutations or other alterations (e.g., translocations or inversions) that may be correlated with disease. This process requires a physical map of the chromosomal region containing the disease-gene of interest along with associated markers. A physical map is necessary for s determining the nucleotide sequence of and order of marker genes on a particular chromosomal region. Physical mapping techniques are well known in the art and require the generation of overlapping sets of cloned DNA fragments from a particular organelle, chromosome, or genome.
These clones are analyzed to reconstruct and catalog their order. Once the position of a marker is determined, the DNA from that region is obtained by consulting the catalog and selecting clones from io that region. The gene of interest is located through positional cloning techniques using hybridization or similar methods.
Diagnostic Uses The sptm of the present invention may be used to design probes useful in diagnostic assays.
i5 Such assays, well known to those skilled in the art, may be used to detect or confirm conditions, disorders, or diseases associated with abnormal levels of sptm expression.
Labeled probes developed from sptm sequences are added to a sample under hybridizing conditions of desired stringency. In some instances, sptm, or fragments or oligonucleotides derived from sptm, may be used as primers in amplification steps prior to hybridization. The amount of hybridization complex formed is quantified 2o and compared with standards for that cell or tissue. If sptm expression varies significantly from the standard, the assay indicates the presence of the condition, disorder, or disease. Qualitative or quantitative diagnostic methods may include northern, dot blot, or other membrane or dip-stick based technologies or multiple-sample format technologies such as PCR, enzyme-linked immunosorbent assay (ELISA)-like, pin, or chip-based assays.
z5 The probes described above may also be used to monitor the progress of conditions, disorders, or diseases associated with abnormal levels of sptm expression, or to evaluate the efficacy of a particular therapeutic treatment. The candidate probe may be identified from the sptm that are specific to a given human tissue and have not been observed in GenBank or other genome databases.
Such a probe may be used in animal studies, preclinical tests, clinical trials, or in monitoring the 3 o treatment of an individual patient. In a typical process, standard expression is established by methods well known in the art for use as a basis of comparison, samples from patients affected by the disorder or disease are combined with the probe to evaluate any deviation from the standard profile, and a therapeutic agent is administered and effects are monitored to generate a treatment profile. Efficacy is evaluated by determining whether the expression progresses toward or returns to the standard 35 normal pattern. Treatment profiles may be generated over a period of several days or several months.

Statistical methods well known to those skilled in the art may be use to determine the significance of such therapeutic agents.
The polynucleotides are also useful for identifying individuals from minute biological samples, for example, by matching the RFLP pattern of a sample's DNA to that of an individual's s DNA. The polynucleotides of the present invention can also be used to determine the actual base-by-base DNA sequence of selected portions of an individual's genome.
These sequences can be used to prepare PCR primers for amplifying and isolating such selected DNA, which can then be sequenced. Using this technique, an individual can be identified through a unique set of DNA
sequences. Once a unique ID database is established for an individual, positive identification of that to individual can be made from extremely small tissue samples.
In a particular aspect, oligonucleotide primers derived from the sptm of the invention may be used to detect single nucleotide polymorphisms (SNPs). SNPs are substitutions, insertions and deletions that are a frequent cause of inherited or acquired genetic disease in humans. Methods of SNP detection include, but are not limited to, single-stranded conformation polymorphism (SSCP) is and fluorescent SSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from sptm are used to amplify DNA using the polymerase chain reaction (PCR). The DNA may be derived, for example, from diseased or normal tissue, biopsy samples, bodily fluids, and the like. SNPs in the DNA cause differences in the secondary and tertiary structures of PCR products in single-stranded form, and these differences are detectable using gel electrophoresis in non-denaturing gels. In 2o fSCCP, the oligonucleotide primers are fluorescently labeled, which allows detection of the amplimers in high-throughput equipment such as DNA sequencing machines.
Additionally, sequence database analysis methods, termed in silico SNP (isSNP), are capable of identifying polymorphisms by comparing the sequences of individual overlapping DNA fragments which assemble into a common consensus sequence. These computer-based methods filter out sequence variations due to 25 laboratory preparation of DNA and sequencing errors using statistical models and automated analyses of DNA sequence chromatograms. In the alternative, SNPs may be detected and characterized by mass spectrometry using, for example, the high throughput MASSARRAY system (Sequenom, Inc., San Diego CA).
DNA-based identification techniques are critical in forensic technology. DNA
sequences 3 o taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, etc., can be amplified using, e.g., PCR, to identify individuals. (See, e.g., Erlich, H.
(1992) PCR TechnoloQV, Freeman and Co., New York, NY). Similarly, polynucleotides of the present invention can be used as polymorphic markers.
There is also a need for reagents capable of identifying the source of a particular tissue.
3 5 Appropriate reagents can comprise, for example, DNA probes or primers prepared from the sequences of the present invention that are specific for particular tissues.
Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue cultures for contamination.
The polynucleotides of the present invention can also be used as molecular weight markers on nucleic acid gels or Southern blots, as diagnostic probes for the presence of a specific mRNA in a particular cell type, in the creation of subtracted cDNA libraries which aid in the discovery of novel polynucleotides, in selection and synthesis of oligomers for attachment to an array or other support, and as an antigen to elicit an immune response.
Disease Model Svstems Using-sptm The sptm of the invention or their mammalian homologs may be "knocked out" in an animal to model system using homologous recombination in embryonic stem (ES) cells.
Such techniques are well known in the art and are useful for the generation of animal models of human disease. (See, e.g., U.S. Patent Number 5,175,383 and U.S. Patent Number 5,767,337.) For example, mouse ES cells, such as the mouse 129/SvJ cell line, are derived from the early mouse embryo and grown in culture.
The ES cells are transformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphotransferase gene (neo; Capecchi, M.R. (1989) Science 244:1288-1292).
The vector integrates into the corresponding region of the host genome by homologous recombination. Alternatively, homologous recombination takes place using the Cre-IoxP system to knockout a gene of interest in a tissue- or developmental stage-specific manner (March, J.D. (1996) Clin. Invest. 97:1999-2002; Wagner, K.U. et al. (1997) Nucleic Acids Res.
25:4323-4330).
2o Transformed ES cells are identified and nucroinjected into mouse cell blastocysts such as those from the C57BL/6 mouse strain. The blastocysts are surgically transferred to pseudopregnant dams, and the resulting chimeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents.
The sptm of the invention may also be manipulated in vitro in ES cells derived from human blastocysts. Human ES cells have the potential to differentiate into at least eight separate cell lineages including endoderm, mesoderm, and ectodermal cell types. These cell lineages differentiate into, for example, neural cells, hematopoietic lineages, and cardiomyocytes (Thomson, J.A. et al.
(1998) Science 282:1145-1147).
The sptm of the invention can also be used to create "knockin" humanized animals (pigs) or 3o transgenic animals (mice or rats) to model human disease. With knockin technology, a region of sptm is injected into animal ES cells, and the injected sequence integrates into the animal cell genome.
Transformed cells are injected into blastulae, and the blastulae are implanted as described above.
Transgenic progeny or inbred lines are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease. Alternatively, a mammal inbred to overexpress sptm, resulting, e.g., in the secretion of SPTM in its milk, may also serve as a convenient source of that protein (Janne, J. et al. ( 1998) Biotechnol. Annu. Rev. 4:55-74).

Screening Assays SPTM encoded by polynucleotides of the present invention may be used to screen for molecules that bind to or are bound by the encoded polypeptides. The binding of the polypeptide and the molecule may activate (agonist), increase, inhibit (antagonist), or decrease activity of the polypeptide or the bound molecule. Examples of such molecules include antibodies, oligonucleotides, proteins (e.g., receptors), or small molecules.
Preferably, the molecule is closely related to the natural ligand of the polypeptide, e.g., a ligand or fragment thereof, a natural substrate, or a structural or functional mimetic. (See, Coligan et al., (1991) Current Protocols in Immunology 1(2): Chapter 5.) Similarly, the molecule can be closely to related to the natural receptor to which the polypeptide binds, or to at least a fragment of the receptor, e.g., the active site. In either case, the molecule can be rationally designed using known techniques.
Preferably, the screening for these molecules involves producing appropriate cells which express the polypeptide, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or E. coli. Cells expressing the polypeptide or cell membrane fractions i5 which contain the expressed polypeptide are then contacted with a test compound and binding, stimulation, or inhibition of activity of either the polypeptide or the molecule is analyzed.
An assay may simply test binding of a candidate compound to the polypeptide, wherein binding is detected by a fluorophore, radioisotope, enzyme conjugate, or other detectable label.
Alternatively, the assay may assess binding in the presence of a labeled competitor.
2o Additionally, the assay can be carried out using cell-free preparations, polypeptide/molecule affixed to a solid support, chemical libraries, or natural product mixtures.
The assay may also simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide, measuring polypeptide/molecule activity or binding, and comparing the polypeptide/molecule activity or binding to a standard.
25 Preferably, an ELISA assay using, e.g., a monoclonal or polyclonal antibody, can measure polypeptide level in a sample. The antibody can measure polypeptide level by either binding, directly or indirectly, to the polypeptide or by competing with the polypeptide for a substrate.
All of the above assays can be used in a diagnostic or prognostic context. The molecules discovered using these assays can be used to treat disease or to bring about a particular result in a 3o patient (e.g., blood vessel growth) by activating or inhibiting the polypeptide/molecule. Moreover, the assays can discover agents which may inhibit or enhance the production of the polypeptide from suitably manipulated cells or tissues.
Transcript Imaging Another embodiment relates to the use of sptm to develop a transcript image of a tissue or s5 cell type. A transcript image is the collective pattern of gene expression by a particular tissue or cell type under given conditions and at a given time. This pattern of gene expression is defined by the number of expressed genes, their abundance, and their function. Thus the sptm of the present invention may be used to develop a transcript image of a tissue or cell type by hybridizing, preferably in a microarray format, the sptm of the present invention to the totality of transcripts or reverse transcripts of a tissue or cell type. The resultant transcript image would provide a profile of gene activity pertaining to cell signaling.
Transcript images which profile sptm expression may be generated using transcripts isolated from tissues, cell lines, biopsies, or other biological samples. The transcript image may thus reflect sptm expression in vivo, as in the case of a tissue or biopsy sample, or in vitro, as in the case of a cell line. Transcript images may be used to profile sptm expression in distinct tissue types. This process to can be used to determine cell signaling activity in a particular tissue type relative to this activity in a different tissue type. Transcript images may be used to generate a profile of sptm expression characteristic of diseased tissue. Transcript images of tissues before and after treatment may be used for diagnostic purposes, to monitor the progression of disease, and to monitor the efficacy of drug treatments for diseases which affect cell signaling.
Transcript images which profile sptm expression may also be used in conjunction with in vitro model systems and preclinical evaluation of pharmaceuticals. Transcript images of cell lines can be used to assess cell signaling activity and/or to identify cell lines that lack or nusregulate this activity. Such cell lines may then be treated with pharmaceutical agents, and a transcript image following treatment may indicate the efficacy of these agents in restoring desired levels of this 2 o activity. A similar approach may be used to assess the toxicity of pharmaceutical agents as reflected by undesirable changes in cell signaling. Candidate pharmaceutical agents may be evaluated by comparing their associated transcript images with those of pharmaceutical agents of known effectiveness.
Antisense Molecules 2 5 The polynucleotides of the present invention are useful in antisense technology. Antisense technology or therapy relies on the modulation of expression of a target protein through the specific binding of an antisense sequence to a target sequence encoding the target protein or directing its expression. (See, e.g., Agrawal, S., ed. (1996) Antisense Therapeutics, Humana Press Inc., Totawa NJ; Alama, A. et al. (1997) Pharmacol. Res. 36(3):171-178; Crooke, S.T. (1997) Adv. Pharmacol.
30 40:1-49; Sharma, H.W. and R. Narayanan (1995) Bioessays 17(12):1055-1063;
and Lavrosky, Y. et al. (1997) Biochem. Mol. Med. 62(1):11-22.) An antisense sequence is a polynucleotide sequence capable of specifically hybridizing to at least a portion of the target sequence. Antisense sequences bind to cellular mRNA and/or genomic DNA, affecting translation and/or transcription. Antisense sequences can be DNA, RNA, or nucleic acid mimics and analogs. (See, e.g., Rossi, J.J. et al. (1991) 35 Antisense Res. Dev. 1(3):285-288; Lee, R. et al. (1998) Biochemistry 37(3):900-1010; Pardridge, W.M. et al. (1995) Proc. Natl. Acad. Sci. USA 92(12):5592-5596; and Nielsen, P. E. and Haaima, G.

(1997) Chem. Soc. Rev. 96:73-78.) Typically, the binding which results in modulation of expression occurs through hybridization or binding of complementary base pairs. Antisense sequences can also bind to DNA duplexes through specific interactions in the major groove of the double helix.
The polynucleotides of the present invention and fragments thereof can be used as antisense sequences to modify the expression of the polypeptide encoded by sptm. The antisense sequences can be produced ex vivo, such as by using any of the ABI nucleic acid synthesizer series (PE
Biosystems) or other automated systems known in the art. Antisense sequences can also be produced biologically, such as by transforming an appropriate host cell with an expression vector containing the sequence of interest. (See, e.g., Agrawal, su ra.) to In therapeutic use, any gene delivery system suitable for introduction of the antisense sequences into appropriate target cells can be used. Antisense sequences can be delivered intracellularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the cellular sequence encoding the target protein. (See, e.g., Slater, J.E., et al. (1998) J. Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K.J., et al. (1995) 9(13):1288-1296.) Antisense sequences can also be introduced intracellularly through the use of viral vectors, such as retrovirus and adeno-associated virus vectors. (See, e.g., Miller, A.D. (1990) Blood 76:271; Ausubel, F.M. et al. (1995) Current Protocols in Molecular BioloQV, John Wiley &
Sons, New York NY; Uckert, W. and W. Walther (1994) Pharmacol. Ther. 63(3):323-347.) Other gene delivery mechanisms include liposome-derived systems, artificial viral envelopes, and other 2o systems known in the art. (See> e.g., Rossi> J.J. (1995) Br. Med. Bull.
51(1):217-225; Boado, R.J. et al. (1998) J. Pharm. Sci. 87(11):1308-1315; and Morris> M.C. et al. (1997) Nucleic Acids Res.
25( 14):2730-2736.) Expression In order to express a biologically active SPTM, the nucleotide sequences encoding SPTM or z5 fragments thereof may be inserted into an appropriate expression vector, 1.e., a vector which contains the necessary elements for transcriptional and translational control of the inserted coding sequence in a suitable host. Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding SPTM and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA
techniques, 3o synthetic techniques, and in vivo genetic recombination. (See, e.g., Sambrook, supra, Chapters 4, 8, 16, and 17; and Ausubel, supra, Chapters 9, I0, 13, and 16.) A variety of expression vector/host systems may be utilized to contain and express sequences encoding SPTM. These include, but are not linuted to, nucroorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors;
yeast transformed 35 with yeast expression vectors; insect cell systems infected with viral expression vectors (e.g., baculovirus); plant cell systems transformed with viral expression vectors (e.g., cauliflower mosaic virus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal (mammalian) cell systems. (See, e.g., Sambrook, su ra; Ausubel, 1995, su~a, Van Heeke, G. and S.M. Schuster (1989) J. Biol. Chem. 264:5503-5509; Bitter, G.A. et al. (1987) Methods Enzymol. 153:516-544; Scorer, C.A. et al. (1994) Bio/Technology 12:181-184;
s Engelhard, E.K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227;
Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945; Takamatsu, N. (1987) EMBO J. 6:307-311; Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Brogue, R. et al. (1984) Science 224:838-843; Winter, J.
et al. (1991) Results Probl. Cell Differ. 17:85-105; The McGraw Hill Yearbook of Science and TechnoloQy (1992) McGraw Hill, New York NY, pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad.
to Sci. USA 81:3655-3659; and Harrington, J.J. et al. (1997) Nat. Genet.
15:345-355.) Expression vectors derived from retroviruses, adenoviruses, or herpes or vaccinia viruses, or from various bacterial plasmids, may be used for delivery of nucleotide sequences to the targeted organ, tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther.
5(6):350-356; Yu, M. et al., (1993) Proc. Natl. Acad. Sci. USA 90(13):6340-6344; Buller, R.M. et al. (1985) Nature 15 317(6040):813-815; McGregor, D.P. et al. (1994) Mol. Immunol. 31(3):219-226; and Verma, LM.
and N. Somia (1997) Nature 389:239-242.) The invention is not limited by the host cell employed.
For long term production of recombinant proteins in mammalian systems, stable expression of SPTM in cell lines is preferred. For example, sequences encoding SPTM can be transformed into cell lines using expression vectors which may contain viral origins of replication and/or endogenous zo expression elements and a selectable marker gene on the same or on a separate vector. Any number of selection systems may be used to recover transformed cell lines. (See, e.g., Wigler, M. et al.
(1977) Cell 11:223-232; Lowy, I. et al. (1980) Cell 22:817-823.; Wigler, M. et al. (1980) Proc. Natl.
Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol.
150:1-14; Hartman, S.C. and R.C.Mulligan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051; Rhodes, C.A. (1995) z5 Methods Mol. Biol. 55:121-131.) Therapeutic Uses of sptm The sptm of the invention may be used for somatic or germline gene therapy.
Gene therapy may be performed to (i) correct a genetic deficiency (e.g., in the cases of severe combined immunodeficiency (SCID)-X1 disease characterized by X-linked inheritance (Cavazzana-Calvo, M.
3 o et al. (2000) Science 288:669-672), severe combined immunodeficiency syndrome associated with an inherited adenosine deaminase (ADA) deficiency (Blaese, R.M. et al. ( 1995) Science 270:475-480;
Bordignon, C. et al. (1995) Science 270:470-475), cystic fibrosis (Zabner, J.
et al. (1993) Cell 75:207-216; Crystal, R.G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R.G. et al. (1995) Hum. Gene Therapy 6:667-703), thalassemias, familial hypercholesterolenva, and hemophilia 35 resulting from Factor VIII or Factor IX deficiencies (Crystal, R.G. (1995) Science 270:404-410;
Verma, LM. and Somia, N. ( 1997) Nature 389:239-242)), (ii) express a conditionally lethal gene product (e.g., in the case of cancers which result from unregulated cell proliferation), or (iii) express a protein which affords protection against intracellular parasites (e.g., against human retroviruses, such as human immunodeficiency virus (HIV) (Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad. Sci. USA. 93:11395-11399), hepatitis B or C
virus (HBV, HCV);
s fungal parasites, such as Candida albicans and Paracoccidioides brasiliensis; and protozoan parasites such as Plasmodium falciparum and Trvnanosoma cruzi). In the case where a genetic deficiency in sptm expression or regulation causes disease, the expression of sptm from an appropriate population of transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.
In a further embodiment of the invention, diseases or disorders caused by deficiencies in to sptm are treated by constructing mammalian expression vectors comprising sptm and introducing these vectors by mechanical means into sptm-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vitro include (i) direct DNA microinjection into individual cells, (ii) ballistic gold particle delivery, (iii) liposome-mediated transfection, (iv) receptor-mediated gene transfer, and (v) the use of DNA transposons (Morgan, R.A. and Anderson, W.F.
(1993) Annu. Rev.
15 Biochem. 62:191-217; Ivics, Z. (1997) Cell 91:501-510; Boulay, J-L. and Recipon, H. (1998) Curr.
Opin. Biotechnol. 9:445-450).
Expression vectors that may be effective for the expression of sptm include, but are not limited to, the PCDNA 3.1, EPTTAG, PRCCMV2, PREP, PVAX vectors (Invitrogen, Carlsbad CA), PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla CA), and PTET-OFF, 2o PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto CA). The sptm of the invention may be expressed using (i) a constitutively active promoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), or ~i-actin genes), (ii) an inducible promoter (e.g., the tetracycline-regulated promoter (Gossen, M. and Bujard, H.
(1992) Proc. Natl.
Acad. Sci. U.S.A. 89:5547-5551; Gossen, M. et al., (1995) Science 268:1766-1769; Rossi, F.M.V.
2s and Blau, H.M. (1998) Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REX
plasmid (Invitrogen)); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter (Rossi, F.M.V. and Blau, H.M. su ra)), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding SPTM from a normal individual.
3 o Commercially available liposome transformation kits (e.g., the PERFECT

TRANSFECTION KIT, available from Invitrogen) allow one with ordinary skill in the art to deliver polynucleotides to target cells in culture and require minimal effort to optimize experimental parameters. In the alternative, transformation is performed using the calcium phosphate method (Graham, F.L. and Eb, A.J. (1973) Virology 52:456-467), or by electroporation (Neumann, E. et al.
35 (1982) EMBO J. 1:841-845). The introduction of DNA to primary cells requires modification of these standardized mammalian transfection protocols.

In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to sptm expression are treated by constructing a retrovirus vector consisting of (i) sptm under the control of an independent promoter or the retrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNA packaging signals, and (iii) a Rev-responsive element (RRE) along with additional retrovirus cis-acting RNA sequences and coding sequences required for efficient vector propagation.
Retrovirus vectors (e.g., PFB and PFBNEO) are commercially available (Stratagene) and are based on published data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. U.S.A.
92:6733-6737), incorporated by reference herein. The vector is propagated in an appropriate vector producing cell line (VPCL) that expresses an envelope gene with a tropism for receptors on the target cells or a promiscuous 1o envelope protein such as VSVg (Armentano, D. et al. (1987) J. Virol.
61:1647-1650; Bender, M.A. et al. (1987) J. Virol. 61:1639-1646; Adam, M.A. and Miller, A.D. (1988) J.
Virol. 62:3802-3806; Dull, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey, R. et al. (1998) J. Virol.
72:9873-9880). U.S.
Patent Number 5,910,434 to Rigg ("Method for obtaining retrovirus packaging cell lines producing high transducing efficiency retroviral supernatant") discloses a method for obtaining retrovirus packaging cell lines and is hereby incorporated by reference. Propagation of retrovirus vectors, transduction of a population of cells (e.g., CD4+ T-cells), and the return of transduced cells to a patient are procedures well known to persons skilled in the art of gene therapy and have been well documented (Ranga, U. et al. (1997) J. Virol. 71:7020-7029; Bauer, G. et al.
(1997) Blood 89:2259-2267; Bonyhadi, M.L. (1997) J. Virol. 71:4707-4716; Ranga, U. et al. (1998) Proc. Natl. Acad. Sci.
2o U.S.A. 95:1201-1206; Su, L. (1997) Blood 89:2283-2290).
In the alternative, an adenovirus-based gene therapy delivery system is used to deliver sptm to cells which have one or more genetic abnormalities with respect to the expression of sptm. The construction and packaging of adenovirus-based vectors are well known to those with ordinary skill in the art. Replication defective adenovirus vectors have proven to be versatile for importing genes z5 encoding imrnunoregulatory proteins into intact islets in the pancreas (Csete, M.E. et al. (1995) Transplantation 27:263-268). Potentially useful adenoviral vectors are described in U.S. Patent Number 5,707,618 to Armentano ("Adenovirus vectors for gene therapy"), hereby incorporated by reference. For adenoviral vectors, see also Antinozzi, P.A. et al. (1999) Annu. Rev. Nutr.
19:511-544 and Verma, LM. and Somia, N. (1997) Nature 18:389:239-242, both incorporated by 3 o reference herein.
In another alternative, a herpes-based, gene therapy delivery system is used to deliver sptm to target cells which have one or more genetic abnormalities with respect to the expression of sptm.
The use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing sptm to cells of the central nervous system, for which HSV has a tropism. The construction and 35 packaging of herpes-based vectors are well known to those with ordinary skill in the art. A
replication-competent herpes simplex virus (HSV) type 1-based vector has been used to deliver a reporter gene to the eyes of primates (Liu, X. et al. (1999) Exp. Eye Res.169:385-395). The construction of a HSV-1 virus vector has also been disclosed in detail in U.S.
Patent Number 5,804,413 to DeLuca ("Herpes simplex virus strains for gene transfer"), which is hereby incorporated by reference. U.S. Patent Number 5,804,413 teaches the use of recombinant HSV
d92 which consists of a genome containing at least one exogenous gene to be transferred to a cell under the control of the appropriate promoter for purposes including human gene therapy.
Also taught by this patent are the construction and use of recombinant HSV strains deleted for ICP4, ICP27 and ICP22.
For HSV vectors, see also Goins, W. F. et al. 1999 J. Virol. 73:519-532 and Xu, H. et al., (1994) Dev. Biol. 163:152-161, hereby incorporated by reference. The manipulation of cloned herpesvirus to sequences, the generation of recombinant virus following the transfection of multiple plasmids , containing different segments of the large herpesvirus genomes, the growth and propagation of herpesvirus, and the infection of cells with herpesvirus are techniques well known to those of ordinary skill in the art.
In another alternative, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver sptm to target cells. The biology of the prototypic alphavirus, Semliki Forest Virus (SFV), has been studied extensively and gene transfer vectors have been based on the SFV genome (Garoff, H. and Li, K-J. (1998) Curr. Opin. Biotech. 9:464-469). During alphavirus RNA
replication, a subgenomic RNA is generated that normally encodes the viral capsid proteins.
This subgenomic RNA replicates to higher levels than the full-length genomic RNA, resulting in the overproduction of 2o capsid proteins relative to the viral proteins with enzymatic activity (e.g., protease and polymerase).
Similarly, inserting sptm into the alphavirus genome in place of the capsid-coding region results in the production of a large number of sptm RNAs and the synthesis of high levels of SPTM in vector transduced cells. While alphavirus infection is typically associated with cell lysis within a few days, the ability to establish a persistent infection in hamster normal kidney cells (BHK-21) with a variant of Sindbis virus (SIN) indicates that the lytic replication of alphaviruses can be altered to suit the needs of the gene therapy application (Dryga, S.A. et al. (1997) Virology 228:74-83). The wide host range of alphaviruses will allow the introduction of SPTM into a variety of cell types. The specific transduction of a subset of cells in a population may require the sorting of cells prior to transduction.
The methods of manipulating infectious cDNA clones of alphaviruses, performing alphavirus cDNA
3o and RNA transfections, and performing alphavirus infections, are well known to those with ordinary skill in the art.
Antibodies Anti-SPTM antibodies may be used to analyze protein expression levels. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, and Fab fragments.

For descriptions of and protocols of antibody technologies, see, e.g., Pound J.D. ( 1998) Immunochemical Protocols, Humana Press, Totowa, NJ.
The amino acid sequence encoded by the sptm of the Sequence Listing may be analyzed by appropriate software (e.g., LASERGENE NAVIGATOR software, DNASTAR) to determine regions s of high immunogenicity. The optimal sequences for immunization are selected from the C-terminus, the N-terminus, and those intervening, hydrophilic regions of the polypeptide which are likely to be exposed to the external environment when the polypeptide is in its natural conformation. Analysis used to select appropriate epitopes is also described by Ausubel (1997, supra, Chapter 11.7).
Peptides used for antibody induction do not need to have biological activity;
however, they must be to antigenic. Peptides used to induce specific antibodies may have an amino acid sequence consisting of at five amino acids, preferably at least 10 amino acids, and most preferably l5 amino acids. A
peptide which mimics an antigenic fragment of the natural polypeptide may be fused with another protein such as keyhole limpet cyanin (KLH; Sigma, St. Louis MO) for antibody production. A
peptide encompassing an antigenic region may be expressed from an sptm, synthesized as described 15 above, or purified from human cells.
Procedures well known in the art may be used for the production of antibodies.
Various hosts including mice, goats, and rabbits, may be immunized by injection with a peptide. Depending on the host species, various adjuvants may be used to increase immunological response.
In one procedure, peptides about 15 residues in length may be synthesized using an ABI
zo 431A peptide synthesizer (PE Biosystems) using fmoc-chemistry and coupled to KLH (Sigma) by reaction with M-maleimidobenzoyl-N-hydroxysuccinimide ester (Ausubel, 1995, su ra . Rabbits are immunized with the peptide-KLH complex in complete Freund's adjuvant. The resulting antisera are tested for antipeptide activity by binding the peptide to plastic, blocking with 1 % bovine serum albumin (BSA), reacting with rabbit antisera, washing, and reacting with radioiodinated goat anti-25 rabbit IgG. Antisera with antipeptide activity are tested for anti-SPTM
activity using protocols well known in the art, including ELISA, radioimmunoassay (RIA), and immunoblotting.
In another procedure, isolated and purified peptide may be used to immunize mice (about 100 pg of peptide) or rabbits (about 1 mg of peptide). Subsequently, the peptide is radioiodinated and used to screen the immunized animals' B-lymphocytes for production of antipeptide antibodies.
3o Positive cells are then used to produce hybridomas using standard techniques. About 20 mg of peptide is sufficient for labeling and screening several thousand clones.
Hybridomas of interest are detected by screening with radioiodinated peptide to identify those fusions producing peptide-specific monoclonal antibody. In a typical protocol, wells of a multi-well plate (FAST, Becton-Dickinson, Palo Alto, CA) are coated with affinity-purified, specific rabbit-anti-mouse (or suitable 35 anti-species IgG) antibodies at 10 mg/ml. The coated wells are blocked with 1 % BSA and washed and exposed to supernatants from hybridomas. After incubation, the wells are exposed to radiolabeled peptide at 1 mg/ml.
Clones producing antibodies bind a quantity of labeled peptide that is detectable above background. Such clones are expanded and subjected to 2 cycles of cloning.
Cloned hybridomas are injected into pristane-treated mice to produce ascites, and monoclonal antibody is purified from the ascitic fluid by affinity chromatography on protein A (Amersham Pharmacia Biotech). Several procedures for the production of monoclonal antibodies, including in vitro production, are described in Pound su ra). Monoclonal antibodies with antipeptide activity are tested for anti-SPTM activity using protocols well known in the art, including ELISA, RIA, and immunoblotting.
to Antibody fragments containing specific binding sites for an epitope may also be generated.
For example, such fragments include, but are not limited to, the F(ab~2 fragments produced by pepsin digestion of the antibody molecule, and the Fab fragments generated by reducing the disulfide bridges of the F(ab~2 fragments. Alternatively, construction of Fab expression libraries in filamentous bacteriophage allows rapid and easy identification of monoclonal fragments with desired specificity (Pound, supra, Chaps. 45-47). Antibodies generated against polypeptide encoded by sptm can be used to purify and characterize full-length SPTM protein and its activity, binding partners, etc.
Assays Using Antibodies Anti-SPTM antibodies may be used in assays to quantify the amount of SPTM
found in a 2o particular human cell. Such assays include methods utilizing the antibody and a label to detect expression level under normal or disease conditions. The peptides and antibodies of the invention may be used with or without modification or labeled by joining them, either covalently or noncovalently, with a reporter molecule.
Protocols for detecting and measuring protein expression using either polyclonal or monoclonal antibodies are well known in the art. Examples include ELISA, RIA, and fluorescent activated cell sorting (FACS). Such immunoassays typically involve the formation of complexes between the SPTM and its specific antibody and the measurement of such complexes. These and other assays are described in Pound (su ra).
Without further elaboration, it is believed that one skilled in the art can, using the preceding 3o description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
The disclosures of all patents, applications, and publications mentioned above and below, in particular U.S. Ser. No. 60/147,501, and U.S. Ser. No. 60/147,500 are hereby expressly incorporated by reference.

EXAMPLES
I. Construction of cDNA Libraries RNA was purchased from CLONTECH Laboratories, Inc. (Palo Alto CA) or isolated from various tissues. Some tissues were homogenized and lysed in guanidinium isothiocyanate, while others were homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TRIZOL (Life Technologies), a monophasic solution of phenol and guanidine isothiocyanate. The resulting lysates were centrifuged over CsCI cushions or extracted with chloroform. RNA was precipitated with either isopropanol or sodium acetate and ethanol, or by other routine methods.
Phenol extraction and precipitation of RNA were repeated as necessary to increase RNA
to purity. In most cases, RNA was treated with DNase. For most libraries, poly(A+) RNA was isolated using oligo d(T)-coupled paramagnetic particles (Promega Corporation (Promega), Madison WI), OLIGOTEX latex particles (QIAGEN, Inc. (QIAGEN), Valencia CA), or an OLIGOTEX
mRNA
purification kit (QIAGEN). Alternatively, RNA was isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA purification kit (Ambion, Inc., Austin TX).
In some cases, Stratagene was provided with RNA and constructed the corresponding cDNA
libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed with the UNIZAP
vector system (Stratagene Cloning Systems, Inc. (Stratagene), La Jolla CA) or SUPERSCRIPT
plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, Chapters 5.1 through 6.6.) Reverse transcription was 2o initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters were ligated to double stranded cDNA, and the cDNA was digested with the appropriate restriction enzyme or enzymes. For most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL SI000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel electrophoresis. cDNAs were ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT
plasmid (Stratagene), pSPORTI plasmid (Life Technologies), or pINCY (Incyte). Recombinant plasmids were transformed into competent E. coli cells including XL1-Blue, XL1-BIueMRF, or SOLR from Stratagene or DHSa, DHlOB, or ElectroMAX DH10B from Life Technologies.
3 o II. Isolation of cDNA Clones Plasmids were recovered from host cells by in vivo excision using the UNIZAP
vector system (Stratagene) or by cell lysis. Plasmids were purified using at least one of the following: the Magic or WIZARD Minipreps DNA purification system (Promega); the AGTC Miniprep purification kit (Edge BioSystems, Gaithersburg MD); and the QIAWELL 8, QIAWELL 8 Plus, and QIAWELL 8 Ultra plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification kit (QIAGEN). Following precipitation, plasmids were resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4°C.
Alternatively, plasmid DNA was amplified from host cell lysates using direct link PCR in a high-throughput format. (Rao, V.B. (1994) Anal. Biochem. 216:1-14.) Host cell lysis and thermal cycling steps were carried out in a single reaction mixture. Samples were processed and stored in 384-well plates, and the concentration of amplified plasmid DNA was quantified fluorometrically using PICOGREEN dye (Molecular Probes, Inc. (Molecular Probes), Eugene OR) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland).
to III. Sequencing and Analysis cDNA sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 thermal cycler (PE Biosystems) or the PTC-200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific Corp., Sunnyvale CA) or the MICROLAB 2200 liquid transfer system (Hamilton).
cDNA
i5 sequencing reactions were prepared using reagents provided by Amersham Pharmacia Biotech or supplied in ABI sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (PE Biosystems). Electrophoretic separation of cDNA
sequencing reactions and detection of labeled polynucleotides were carried out using the MEGABACE 1000 DNA sequencing system (Molecular Dynamics); the ABI PRISM 373 or 377 sequencing system (PE
Biosystems) in 2 o conjunction with standard ABI protocols and base calling software; or other sequence analysis systems known in the art. Reading frames within the cDNA sequences were identified using standard methods (reviewed in Ausubel, 1997, supra, Chapter 7.7). Some of the cDNA sequences were selected for extension using the techniques disclosed in Example VIII.
2 s IV. Assembly and Analysis of Sequences Component sequences from chromatograms were subject to PHRED analysis and assigned a quality score. The sequences having at least a required quality score were subject to various pre-processing editing pathways to eliminate, e.g., low quality 3' ends, vector and linker sequences, polyA tails, Alu repeats, mitochondrial and ribosomal sequences, bacterial contamination sequences, 3 o and sequences smaller than 50 base pairs. In particular, low-information sequences and repetitive elements (e.g., dinucleotide repeats, Alu repeats, etc.) were replaced by "n's", or masked, to prevent spurious matches.
Processed sequences were then subject to assembly procedures in which the sequences were assigned to gene bins (bins). Each sequence could only belong to one bin.
Sequences in each gene 35 bin were assembled to produce consensus sequences (templates). Subsequent new sequences were added to existing bins using BLASTn (v.1.4 WashU) and CROSSMATCH. Candidate pairs were identified as all BLAST hits having a quality score greater than or equal to 150. Alignments of at least 82% local identity were accepted into the bin. The component sequences from each bin were assembled using a version of PHRAP. Bins with several overlapping component sequences were assembled using DEEP PHRAP. The orientation (sense or antisense) of each assembled template was determined based on the number and orientation of its component sequences.
Template sequences as disclosed in the sequence listing correspond to sense strand sequences (the "forward"
reading frames), to the best determination. The complementary (antisense) strands are inherently disclosed herein. The component sequences which were used to assemble each template consensus sequence are listed in Table 3, along with their positions along the template nucleotide sequences.
to Bins were compared against each other and those having local similarity of at least 82%
were combined and reassembled. Reassembled bins having templates of insufficient overlap (less than 95% local identity) were re-split. Assembled templates were also subject to analysis by STITCHER/EXON MAPPER algorithms which analyze the probabilities of the presence of splice variants, alternatively spliced exons, splice junctions, differential expression of alternative spliced is genes across tissue types or disease states, etc. These resulting bins were subject to several rounds of the above assembly procedures.
Once gene bins were generated based upon sequence alignments, bins were clone joined based upon clone information. If the S' sequence of one clone was present in one bin and the 3' sequence from the same clone was present in a different bin, it was likely that the two bins actually 2 o belonged together in a single bin. The resulting combined bins underwent assembly procedures to regenerate the consensus sequences.
The final assembled templates were subsequently annotated using the following procedure.
Template sequences were analyzed using BLASTn (v2.0, NCBI) versus gbpri (GenBank version 116). "Hits" were defined as an exact match having from 95% local identity over 200 base pairs 25 through 100% local identity over 100 base pairs, or a homolog match having an E-value, i.e. a probability score, of s 1 x 10-g. The hits were subject to frameshift FASTx versus GENPEPT
(GenBank version 116). (See Table 4). In this analysis, a homolog match was defined as having an E-value of <_ 1 x 10-8. The assembly method used above was described in "System and Methods for Analyzing Biomolecular Sequences," U.S.S.N. 09/276,534, filed March 25, 1999, and the LIFESEQ
3 o Gold user manual (Incyte) both incorporated by reference herein.
Following assembly, template sequences were subjected to motif, BLAST, and functional analyses, and categorized in protein hierarchies using methods described in, e.g., "Database System Employing Protein Function Hierarchies for Viewing Biomolecular Sequence Data," U.S.S.N.
08/812,290, filed March 6, 1997; "Relational Database for Storing Biomolecule Information,"
35 U.S.S.N. 08/947,845, filed October 9, 1997; "Project-Based Full-Length Biomolecular Sequence Database," U.S.S.N. 08/811,758, filed March 6, 1997; and "Relational Database and System for Storing Information Relating to Biomolecular Sequences," U.S.S.N. 09/034,807, filed March 4, 1998, all of which are incorporated by reference herein.
The template sequences are further analyzed by translating each template in all three forward reading frames and searching each translation against the Pfam database of hidden Markov model-s based protein families and domains using the HMMER software package (available to the public from Washington University School of Medicine, St. Louis MO). (See also World Wide Web site http://pfam.wustl.edu/ for detailed descriptions of Pfam protein domains and families.) Additionally, the template sequences were translated in all three forward reading frames and each translation was searched against hidden Markov models for signal peptide and transmembrane to domains using the HMMER software package. Construction of hidden Markov models and their usage in sequence analysis has been described. (See, for example, Eddy, S.R.
(1996) Curr. Opin. Str.
Biol. 6:361-365.) Segments of templates which, when translated, contain similarity to signal peptide or transmembrane domain consensus sequences are reported in Table 2. Only those signal peptide or transmembrane hits with a cutoff score of 11 bits or greater are reported. A
cutoff score of 11 bits or 15 greater corresponds to at least about 91-94% true-positives in signal peptide prediction, and at least about 75% true-positives in transmembrane domain prediction.
The results of BLAST analysis as reported in Table 1 may support the results of HMMER
analysis as reported in Table 2 or may suggest alternative or additional properties of template-encoded secretory polypeptides not previously uncovered by HMMER or other analyses.
2o Template sequences are further analyzed using the bioinformatics tools listed in Table 4, or using sequence analysis software known in the art such as MACDNASIS PRO
software (Hitachi Software Engineering, South San Francisco CA) and LASERGENE software (DNASTAR).
Template sequences may be further queried against public databases such as the GenBank rodent, mammalian, vertebrate, prokaryote, and eukaryote databases.
V. Analysis of Polynucleotide Expression Northern analysis is a laboratory technique used to detect the presence of a transcript of a gene and involves the hybridization of a labeled nucleotide sequence to a membrane on which RNAs from a particular cell type or tissue have been bound. (See, e.g., Sambrook, s. unra, ch. 7; Ausubel, 1995, supra, ch. 4 and 16.) Analogous computer techniques applying BLAST are used to search for identical or related molecules in cDNA databases such as GenBank or LIFESEQ (Incyte Pharmaceuticals). This analysis is much faster than multiple membrane-based hybridizations. In addition, the sensitivity of the computer search can be modified to determine whether any particular match is categorized as exact or similar. The basis of the search is the product score, which is defined as:

BLAST Score x Percent Identity x minimum { length(Seq. 1 ), length(Seq. 2) }
The product score takes into account both the degree of similarity between two sequences and the 5 length of the sequence match. The product score is a normalized value between 0 and 100, and is calculated as follows: the BLAST score is multiplied by the percent nucleotide identity and the product is divided by (5 times the length of the shorter of the two sequences). The BLAST score is calculated by assigning a score of +5 for every base that matches in a high-scoring segment pair (HSP), and -4 for every mismatch. Two sequences may share more than one HSP
(separated by to gaps). If there is more than one HSP, then the pair with the highest BLAST
score is used to calculate the product score. The product score represents a balance between fractional overlap and quality in a BLAST alignment. For example, a product score of 100 is produced only for 100%
identity over the entire length of the shorter of the two sequences being compared. A product score of 70 is produced either by 100% identity and 70% overlap at one end, or by 88% identity and 100% overlap at the i5 other. A product score of 50 is produced either by 100% identity and SO%
overlap at one end, or 79% identity and 100% overlap.
VI. Tissue Distribution Profiling A tissue distribution profile is determined for each template by compiling the cDNA library 2o tissue classifications of its component cDNA sequences. Each component sequence, is derived from a cDNA library constructed from a human tissue. Each human tissue is classified into one of the following categories: cardiovascular system; connective tissue; digestive system; embryonic structures; endocrine system; exocrine glands; genitalia, female; genitalia, male; germ cells; heroic and immune system; liver; musculoskeletal system; nervous system; pancreas;
respiratory system;
25 sense organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. Template sequences, component sequences, and cDNA library/tissue information are found in the LIFESEQ
GOLD database (Incyte Genomics, Palo Alto CA).
VII. Transcript Image Analysis 3o Transcript images are generated as described in Seilhamer et al., "Comparative Gene Transcript Analysis," U.S. Patent Number 5,840,484, incorporated herein by reference.
VIII. Extension of Polynucleotide Sequences and Isolation of a Full-length cDNA
Oligonucleotide primers designed using an sptm of the Sequence Listing are used to extend 35 the nucleic acid sequence. One primer is synthesized to initiate 5' extension of the template, and the other primer, to initiate 3' extension of the template. The initial primers may be designed using OLIGO 4.06 software (National Biosciences, Inc. (National Biosciences), Plymouth MN), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC
content of about 50%
or more, and to anneal to the target sequence at temperatures of about 68°C to about 72°C. Any stretch of nucleotides which would result in hairpin structures and primer-primer dimerizations are avoided. Selected human cDNA libraries are used to extend the sequence. If more than one extension is necessary or desired, additional or nested sets of primers are designed.
High fidelity amplification is obtained by PCR using methods well known in the art. PCR is performed in 96-well plates using the PTC-200 thermal cycler (MJ Research).
The reaction mix contains DNA template, 200 nmol of each primer, reaction buffer containing Mg2+, (NH4)zS04, and to B-mercaptoethanol, Taq DNA polymerase (Amersham Pharmacia Biotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase (Stratagene), with the following parameters for primer pair PCI A and PCI B: Step 1: 94°C, 3 min; Step 2: 94°C, 15 sec; Step 3: 60°C, 1 min; Step 4: 68°C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6:
68°C, 5 min; Step 7: storage at 4°C. In the alternative, the parameters for primer pair T7 and SK+ are as follows: Step 1: 94°C, 3 15 min; Step 2: 94°C, 15 sec; Step 3: 57°C, 1 min; Step 4:
68°C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68°C, 5 min; Step 7: storage at 4°C.
The concentration of DNA in each well is determined by dispensing 100 p1 PICOGREEN
quantitation reagent (0.25% (v/v); Molecular Probes) dissolved in 1X Tris-EDTA
(TE) and 0.5 p1 of undiluted PCR product into each well of an opaque fluorimeter plate (Corning Incorporated 20 (Corning), Corning NY), allowing the DNA to bind to the reagent. The plate is scanned in a FLUOROSKAN II (Labsystems Oy) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 p1 to 10 p1 aliquot of the reaction nuxture is analyzed by electrophoresis on a 1 % agarose nuni-gel to determine which reactions are successful in extending the sequence.
The extended nucleotides are desalted and concentrated, transferred to 384-well plates, 2s digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison WI), and sonicated or sheared prior to religation into pUC 18 vector (Amersham Pharmacia Biotech). For shotgun sequencing, the digested nucleotides are separated on low concentration (0.6 to 0.8%) agarose gels, fragments are excised, and agar digested with AGAR ACE
(Promega). Extended clones are religated using T4 ligase (New England Biolabs, Inc., Beverly MA) into pUC 18 vector 30 (Amersham Pharmacia Biotech), treated with Pfu DNA polymerase (Stratagene) to fill-in restriction site overhangs, and transfected into competent E. coli cells. Transformed cells are selected on antibiotic-containing media, individual colonies are picked and cultured overnight at 37°C in 384-well plates in LB/2x carbenicillin liquid media.
The cells are lysed, and DNA is amplified by PCR using Taq DNA polymerase (Amersham 35 Pharmacia Biotech) and Pfu DNA polymerase (Stratagene) with the following parameters: Step 1:
94°C, 3 min; Step 2: 94°C, IS sec; Step 3: 60°C, 1 min;
Step 4: 72°C, 2 min; Step 5: steps 2, 3, and 4 repeated 29 times; Step 6: 72°C, 5 min; Step 7: storage at 4°C. DNA is quantified by PICOGREEN reagent (Molecular Probes) as described above. Samples with low DNA
recoveries are reamplified using the same conditions as described above. Samples are diluted with 20%
dimethysulfoxide (1:2, v/v), and sequenced using DYENAMIC energy transfer sequencing primers and the DYENAMIC DIRECT kit (Amersham Pharmacia Biotech) or the ABI PRISM
BIGDYE
Terminator cycle sequencing ready reaction kit (PE Biosystems).
In like manner, the sptm is used to obtain regulatory sequences (promoters, introns, and enhancers) using the procedure above, oligonucleotides designed for such extension, and an appropriate genomic library.
IX. Labeling of Probes and Southern Hybridization Analyses Hybridization probes derived from the sptm of the Sequence Listing are employed for screening cDNAs, mRNAs, or genomic DNA. The labeling of probe nucleotides between 100 and 1000 nucleotides in length is specifically described, but essentially the same procedure may be used is with larger cDNA fragments. Probe sequences are labeled at room temperature for 30 minutes using a T4 polynucleotide kinase, y3zP-ATP, and O.SX One-Phor-All Plus (Amersham Pharmacia Biotech) buffer and purified using a ProbeQuant G-50 Microcolumn (Amersham Pharmacia Biotech). The probe mixture is diluted to 10' dpm/pg/ml hybridization buffer and used in a typical membrane-based hybridization analysis.
2 o The DNA is digested with a restriction endonuclease such as Eco RV and is electrophoresed through a 0.7% agarose gel. The DNA fragments are transferred from the agarose to nylon membrane (NYTRAN Plus, Schleicher & Schuell, Inc., Keene NH) using procedures specified by the manufacturer of the membrane. Prehybridization is carried out for three or more hours at 68°C, and hybridization is carried out overnight at 68°C. To remove non-specific signals, blots are 25 sequentially washed at room temperature under increasingly stringent conditions, up to O. lx saline sodium citrate (SSC) and 0.5% sodium dodecyl sulfate. After the blots are placed in a PHOSPHORIMAGER cassette (Molecular Dynamics) or are exposed to autoradiography film, hybridization patterns of standard and experimental lanes are compared.
Essentially the same procedure is employed when screening RNA.
X. Chromosome Mapping of sptm The cDNA sequences which were used to assemble SEQ ID NO:1-26 are compared with sequences from the Incyte LIFESEQ database and public domain databases using BLAST and other implementations of the Smith-Waterman algorithm. Sequences from these databases that match SEQ
ID NO:1-26 are assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as PHRAP (Table 4). Radiation hybrid and genetic mapping data available from public resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome Research (WIGR), and Genethon are used to determine if any of the clustered sequences have been previously mapped. Inclusion of a mapped sequence in a cluster will result in the assignment of all sequences of that cluster, including its particular SEQ ID
NO:, to that map location.
The genetic map locations of SEQ ID NO:1-26 are described as ranges, or intervals, of human chromosomes. The map position of an interval, in centiMorgans, is measured relative to the terminus of the chromosome's p-arm. (The centiMorgan (cM) is a unit of measurement based on recombination frequencies between chromosomal markers. On average, 1 cM is roughly equivalent to 1 megabase (Mb) of DNA in humans, although this can vary widely due to hot and cold spots of to recombination.) The cM distances are based on genetic markers mapped by Genethon which provide boundaries for radiation hybrid markers whose sequences were included in each of the clusters.
XI. Microarray Analysis Probe Preparation from Tissue or Cell Samples is Total RNA is isolated from tissue samples using the guanidinium thiocyanate method and polyA+ RNA is purified using the oligo (dT) cellulose method. Each polyA+ RNA
sample is reverse transcribed using MMLV reverse-transcriptase, 0.05 pg/lrl oligo-dT primer (2lmer), 1X first strand buffer, 0.03 units/pl RNase inhibitor, 500 NM dATP, 500 pM dGTP, 5001rM dTTP, 40 pM dCTP, 40 pM dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse transcription 2o reaction is performed in a 25 ml volume containing 200 ng polyA+ RNA with GEMBRIGHT kits (Incyte). Specific control polyA+ RNAs are synthesized by in vitro transcription from non-coding yeast genomic DNA (W. Lei, unpublished). As quantitative controls, the control mRNAs at 0.002 ng, 0.02 ng, 0.2 ng, and 2 ng are diluted into reverse transcription reaction at ratios of 1:100,000, 1:10,000, 1:1000, I :100 (w1w) to sample mRNA respectively. The control mRNAs are diluted into 25 reverse transcription reaction at ratios of 1:3, 3:1, 1:10, 10:1, 1:25, 25:1 (w/w) to sample mRNA
differential expression patterns. After incubation at 37° C for 2 hr, each reaction sample (one with Cy3 and another with Cy5 labeling) is treated with 2.5 ml of 0.5M sodium hydroxide and incubated for 20 minutes at 85°C to the stop the reaction and degrade the RNA.
Probes are purified using two successive CHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, Inc.
so (CLONTECH), Palo Alto CA) and after combining, both reaction samples are ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodium acetate, and 300 ml of 100%
ethanol. The probe is then dried to completion using a SpeedVAC (Savant Instruments Inc., Holbrook NY) and resuspended in 14 p1 5X SSC/0.2% SDS.
Microarray Preparation 35 Sequences of the present invention are used to generate array elements.
Each array element is amplified from bacterial cells containing vectors with cloned cDNA inserts.
PCR amplification uses primers complementary to the vector sequences flanking the cDNA insert.
Array elements are amplified in thirty cycles of PCR from an initial quantity of 1-2 ng to a final quantity greater than 5 pg. Amplified array elements are then purified using SEPHACRYL-400 (Amersham Pharmacia Biotech).
s Purified array elements are immobilized on polymer-coated glass slides.
Glass microscope slides (Corning) are cleaned by ultrasound in 0.1% SDS and acetone, with extensive distilled water washes between and after treatments. Glass slides are etched in 4%
hydrofluoric acid (VWR
Scientific Products Corporation (VWR), West Chester, PA), washed extensively in distilled water, and coated with 0.05% aminopropyl silane (Sigma) in 95% ethanol. Coated slides are cured in a l0 110°C oven.
Array elements are applied to the coated glass substrate using a procedure described in US
Patent No. 5,807,522, incorporated herein by reference. 1 p1 of the array element DNA, at an average concentration of 100 ng/pl, is loaded into the open capillary printing element by a high-speed robotic apparatus. The apparatus then deposits about 5 n1 of array element sample per slide.
15 Microarrays are UV-crosslinked using a STRATALINKER UV-crosslinker (Stratagene).
Microarrays are washed at room temperature once in 0.2% SDS and three times in distilled water.
Non-specific binding sites are blocked by incubation of microarrays in 0.2%
casein in phosphate buffered saline (PBS) (Tropix, Inc., Bedford, MA) for 30 minutes at 60°C followed by washes in 0.2% SDS and distilled water as before.
2 o Hybridization Hybridization reactions contain 9 p1 of probe mixture consisting of 0.2 pg each of Cy3 and Cy5 labeled cDNA synthesis products in 5X SSC, 0.2% SDS hybridization buffer.
The probe mixture is heated to 65°C for 5 minutes and is aliquoted onto the microarray surface and covered with an 1.8 cmz coverslip. The arrays are transferred to a waterproof chamber having a cavity just 25 slightly larger than a microscope slide. The chamber is kept at 100%
humidity internally by the addition of 140 p1 of Sx SSC in a comer of the chamber. The chamber containing the arrays is incubated for about 6.5 hours at 60° C. The arrays are washed for 10 min at 45° C in a first wash buffer (1X SSC, 0.1% SDS), three times for 10 minutes each at 45°C in a second wash buffer (0.1X
SSC), and dried.
3o Detection Reporter-labeled hybridization complexes are detected with a microscope equipped with an Innova 70 mixed gas 10 W laser (Coherent, Inc., Santa Clara CA) capable of generating spectral lines at 488 nm for excitation of Cy3 and at 632 nm for excitation of CyS. The excitation laser light is focused on the array using a 20X microscope objective (Nikon, Inc., Melville NY). The slide 35 containing the array is placed on a computer-controlled X-Y stage on the microscope and raster-scanned past the objective. The 1.8 cm x 1.8 cm array used in the present example is scanned with a resolution of 20 micrometers..
In two separate scans, a mixed gas multiline laser excites the two fluorophores sequentially.
Emitted light is split, based on wavelength, into two photomultiplier tube detectors (PMT 81477, s Hamamatsu Photonics Systems, Bridgewater NJ) corresponding to the two fluorophores.
Appropriate filters positioned between the array and the photomultiplier tubes are used to filter the signals. The emission maxima of the fluorophores used are 565 nm for Cy3 and 650 nm for CyS.
Each array is typically scanned twice, one scan per fluorophore using the appropriate filters at the laser source, although the apparatus is capable of recording the spectra from both fluorophores to simultaneously.
The sensitivity of the scans is typically calibrated using the signal intensity generated by a cDNA control species added to the probe mix at a known concentration. A
specific location on the array contains a complementary DNA sequence, allowing the intensity of the signal at that location to be correlated with a weight ratio of hybridizing species of 1:100,000. When two probes from 15 different sources (e.g., representing test and control cells), each labeled with a different fluorophore, are hybridized to a single array for the purpose of identifying genes that are differentially expressed, the calibration is done by labeling samples of the calibrating cDNA with the two fluorophores and adding identical amounts of each to the hybridization mixture.
The output of the photomultiplier tube is digitized using a 12-bit RTI-835H
analog-to-digital 20 (A/D) conversion board (Analog Devices, Inc., Norwood, MA) installed in an IBM-compatible PC
computer. The digitized data are displayed as an image where the signal intensity is mapped using a linear 20-color transformation to a pseudocolor scale ranging from blue (low signal) to red (high signal). The data is also analyzed quantitatively. Where two different fluorophores are excited and measured simultaneously, the data are first corrected for optical crosstalk (due to overlapping 2 s emission spectra) between the fluorophores using each fluorophore's emission spectrum.
A grid is superimposed over the fluorescence signal image such that the signal from each spot is centered in each element of the grid. The fluorescence signal within each element is then integrated to obtain a numerical value corresponding to the average intensity of the signal. The software used for signal analysis is the GEMTOOLS gene expression analysis program (Incyte).
XII. Complementary Nucleic Acids Sequences complementary to the sptm are used to detect, decrease, or inhibit expression of the naturally occurnng nucleotide. The use of oligonucleotides comprising from about 15 to 30 base pairs is typical in the art. However, smaller or larger sequence fragments can also be used.
Appropriate oligonucleotides are designed from the sptm using OLIGO 4.06 software (National Biosciences) or other appropriate programs and are synthesized using methods standard in the art or ordered from a commercial supplier. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5'sequence and used to prevent transcription factor binding to the promoter sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding and processing of the transcript.
XIII. Expression of SPTM
Expression and purification of SPTM is accomplished using bacterial or virus-based expression systems. For expression of SPTM in bacteria, cDNA is subcloned into an appropriate vector containing an antibiotic resistance gene and an inducible promoter that directs high levels of to cDNA transcription. Examples of such promoters include, but are not limited to, the trp-lac (tac) hybrid promoter and the TS or T7 bacteriophage promoter in conjunction with the lac operator regulatory element. Recombinant vectors are transformed into suitable bacterial hosts, e.g., BL21(DE3). Antibiotic resistant bacteria express SPTM upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression of SPTM in eukaryotic cells is achieved by infecting 15 insect or mammalian cell lines with recombinant Autogranhica californica nuclear polyhedrosis virus (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding SPTM by either homologous recombination or bacterial-mediated transposition involving transfer plasmid intermediates. Viral infectivity is maintained and the strong polyhedrin promoter drives high levels of cDNA transcription. Recombinant baculovirus is used to zo infect Spodoptera fru>yiperda (Sf9) insect cells in most cases, or human hepatocytes, in some cases.
Infection of the latter requires additional genetic modifications to baculovirus. (See e.g., Engelhard, suvra; and Sandig, supra.) In most expression systems, SPTM is synthesized as a fusion protein with, e.g., glutathione S-transferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting rapid, single-step, zs affinity-based purification of recombinant fusion protein from crude cell lysates. GST, a 26 kilodalton enzyme from Schistosoma japonicum, enables the purification of fusion proteins on immobilized glutathione under conditions that maintain protein activity and antigenicity (Amersham Pharmacia Biotech). Following purification, the GST moiety can be proteolytically cleaved from SPTM at specifically engineered sites. FLAG, an 8-amino acid peptide, enables immunoaffinity 3o purification using commercially available monoclonal and polyclonal anti-FLAG antibodies (Eastman Kodak Company, Rochester NY). 6-His, a stretch of six consecutive histidine residues, enables purification on metal-chelate resins (QIAGEN). Methods for protein expression and purification are discussed in Ausubel (1995, su ra, Chapters 10 and 16).
Purified SPTM obtained by these methods can be used directly in the following activity assay.

XIV. Demonstration of SPTM Activity An assay for SPTM activity measures the expression of SPTM on the cell surface. cDNA
encoding SPTM is subcloned into an appropriate mammalian expression vector suitable for high levels of cDNA expression. The resulting construct is transfected into a nonhuman cell line such as s NIH3T3. Cell surface proteins are labeled with biotin using methods known in the art.
Immunoprecipitations are performed using SPTM-specific antibodies, and immunoprecipitated samples are analyzed using SDS-PAGE and immunoblotting techniques. The ratio of labeled immunoprecipitant to unlabeled immunoprecipitant is proportional to the amount of SPTM
expressed on the cell surface.
1o Alternatively, an assay for SPTM activity measures the amount of SPTM in secretory, membrane-bound organelles. Transfected cells as described above are harvested and lysed. The lysate is fractionated using methods known to those of skill in the art, for example, sucrose gradient ultracentrifugation. Such methods allow the isolation of subcellular components such as the Golgi apparatus, ER, small membrane-bound vesicles, and other secretory organelles.
is Immunoprecipitations from fractionated and total cell lysates are performed using SPTM-specific antibodies, and immunoprecipitated samples are analyzed using SDS-PAGE and immunoblotting techniques. The concentration of SPTM in secretory organelles relative to SPTM
in total cell lysate is proportional to the amount of SPTM in transit through the secretory pathway.
2 o XV. Functional Assays SPTM function is assessed by expressing sptm at physiologically elevated levels in manunalian cell culture systems. cDNA is subcloned into a mammalian expression vector containing a strong promoter that drives high levels of cDNA expression. Vectors of choice include pCMV
SPORT (Life Technologies) and pCR3.1 (Invitrogen Corporation, Carlsbad CA), both of which 2 s contain the cytomegalovirus promoter. 5-10 pg of recombinant vector are transiently transfected into a human cell line, preferably of endothelial or hematopoietic origin, using either liposome formulations or electroporation. 1-2 pg of an additional plasmid containing sequences encoding a marker protein are co-transfected.
Expression of a marker protein provides a means to distinguish transfected cells from s o nontransfected cells and is a reliable predictor of cDNA expression from the recombinant vector.
Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP;
CLONTECH), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), an automated laser optics-based technique, is used to identify transfected cells expressing GFP or CD64-GFP and to evaluate the apoptotic state of the cells and other cellular properties.
35 FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding or coincident with cell death. These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in cell size and granularity as measured by forward light scatter and 90 degree side light scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of cell surface and intracellular proteins as measured by reactivity with specific antibodies; and alterations in plasma membrane composition as measured by the binding of fluorescein-conjugated Annexin V protein to the cell surface. Methods in flow cytometry are discussed in Ormerod, M. G. ( 1994) Flow Ctometry, Oxford, New York NY.
The influence of SPTM on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding SPTM and either CD64 or CD64-GFP.
to CD64 and CD64-GFP are expressed on the surface of transfected cells and bind to conserved regions of human immunoglobulin G (IgG). Transfected cells are efficiently separated from nontransfected cells using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Inc., Lake Success NY). mRNA can be purified from the cells using methods well known by those of skill in the art. Expression of mRNA encoding SPTM and other genes of interest can be analyzed by northern analysis or microarray techniques.
XVI. Production of Antibodies SPTM substantially purified using polyacrylamide gel electrophoresis (PAGE;
see, e.g., Harrington, M.G. (1990) Methods Enzymol. 182:488-495), or other purification techniques, is used 2o to immunize rabbits and to produce antibodies using standard protocols.
Alternatively, the SPTM amino acid sequence is analyzed using LASERGENE
software (DNASTAR) to determine regions of high immunogenicity, and a corresponding peptide is synthesized and used to raise antibodies by means known to those of skill in the art. Methods for selection of appropriate epitopes, such as those near the C-terminus or in hydrophilic regions are well described in the art. (See, e.g., Ausubel, 1995, supra, Chapter 11.) Typically, peptides 15 residues in length are synthesized using an ABI 431A
peptide synthesizer (PE Biosystems) using fmoc-chemistry and coupled to KLH (Sigma) by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to increase immunogenicity.
(See, e.g., Ausubel, supra.) Rabbits are immunized with the peptide-KL,H complex in complete Freund's 3 o adjuvant. Resulting antisera are tested for antipeptide activity by, for example, binding the peptide to plastic, blocking with 1 % BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG. Antisera with antipeptide activity are tested for anti-SPTM activity using protocols well known in the art, including ELISA, RIA, and immunoblotting.

XVII. Purification of Naturally Occurring SPTM Using Specific Antibodies Naturally occurring or recombinant SPTM is substantially purified by immunoaffinity chromatography using antibodies specific for SPTM. An immunoaffinity column is constructed by covalently coupling anti-SPTM antibody to an activated chromatographic resin, such as s CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer's instructions.
Media containing SPTM are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of SPTM (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt to antibody/SPTM binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and SPTM is collected.
XVIII. Identification of Molecules Which Interact with SPTM
SPTM, or biologically active fragments thereof, are labeled with'ZSI Bolton-Hunter reagent.
is (See, e.g., Bolton, A.E. and W.M. Hunter (1973) Biochem. J. 133:529-539.) Candidate molecules previously arrayed in the wells of a multi-well plate are incubated with the labeled SPTM, washed, and any wells with labeled SPTM complex are assayed. Data obtained using different concentrations of SPTM are used to calculate values for the number, affinity, and association of SPTM with the candidate molecules.
2o Alternatively, molecules interacting with SPTM are analyzed using the yeast two-hybrid system as described in Fields, S. and O. Song (1989) Nature 340:245-246, or using commercially available kits based on the two-hybrid system, such as the MATCHMAKER system (CLONTECH).
SPTM may also be used in the PATHCALLING process (CuraGen Corp., New Haven CT) which employs the yeast two-hybrid system in a high-throughput manner to determine all 2 s interactions between the proteins encoded by two large libraries of genes (Nandabalan, K. et al.
(2000) U.S. Patent No. 6,057,101).
All publications and patents mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described method and system of the invention 3o will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the above-described modes for carrying out the invention which are obvious to those skilled in the field of molecular biology or 35 related fields are intended to be within the scope of the following claims.

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SEQ Template Start Stop Frame Domain ID ID Type NO:

1 1978.1 401 478 forward TM

2 2588.4 362 454 forward SP

2 2588.4 1552 1626 forward TM

3 201759,3 926 1009 forward SP

4 208184,1 1438 1533 forward SP

4 208184.1 159 242 forward SP

4 208184,1 1194 1271 forward TM

212029,3 128 208 forward SP

b 213446,2 944 1021 forward SP

b 213446.2 614 718 forward SP

b 213446,2 934 1020 forward TM

7 228864,4 1600 1680 forward SP

7 228864.4 116 229 forward SP

7 228864.4 543 638 forward SP

8 229840.3 2861 2938 forward TM

9 231793.2 730 810 forward SP

234137.5 708 806 forward SP

11 234671.14 557 634 forward TM

12 241236.3 1397 1501 forward SP

13 245014.1 1326 1412 forward TM

14 245251.6 826 909 forward SP

252875.1 2388 2468 forward TM

16 252964.2 2954 3037 forward TM

17 267153.7 746 829 forward SP

18 331244.6 413 493 forward TM

19 335484.1 1977 2060 forward TM

19 335484.1 2805 2888 forward TM

337489.2 bbb 746 forward TM

21 359574.5 2571 2657 forward SP

21 359574.5 1845 1931 forward SP

21 359574.5 1665 1760 forward SP

22 360645.5 415 495 forward SP

23 404145.7 2141 2248 forward SP

23 404145.7 Ebb 785 forward SP

24 480119.1 1181 1267 forward SP

24 480119.1 413 499 forward SP

480951.5 2523 2606 forward TM

2b 481257.3 2774 2860 forward TM

S'7 SEQ ID NO: TemplateComponent Start Stop ID ID

1 1978.1 g 1855482 1 217 1 1978,1 3137104H1 1 272 1 1978.1 3137104F6 1 381 1 1978.1 3526040H1 11 304 1 1978.1 3523774H1 11 357 1 1978.1 g 1267790 148 605 1 1978.1 g1267782 148 522 1 1978.1 g1958606 164 580 1 1978.1 3031854H1 269 571 1 1978.1 4832441H1 339 597 1 1978,1 g1775794 353 418 1 1978.1 4142134H1 553 758 1 1978.1 1600481H1 605 800 1 1978.1 1600481F6 605 966 1 1978.1 4379163H1 653 915 1 1978.1 2901551H1 668 927 1 1978.1 1678677H1 677 909 1 1978.1 3842809H1 736 1043 1 1978.1 1793709H1 755 1050 1 1978.1 2773028H1 755 1009 1 1978.1 3602828H1 860 1155 1 1978.1 1610720H1 934 1142 1 1978,1 2366358H1 976 1193 1 1978.1 5497064H1 1036 1265 1 1978,1 3742273H1 1063 1273 1 1978.1 5261375H1 1113 1334 1 1978,1 1378352F1 1149 1688 1 1978.1 1378352H1 1149 1386 1 1978,1 1281776F6 1190 1796 1 1978,1 1281776H1 1190 1453 1 1978.1 2097593H1 1199 1380 1 1978.1 2098893H1 1199 1445 1 1978.1 g714966 1208 1550 1 1978.1 3929766H1 1219 1504 1 1978.1 g1425881 1230 1639 1 1978.1 g989565 1249 1465 1 1978.1 1369088H1 1249 1478 1 1978.1 627100H1 1249 1491 1 1978.1 815413H1 1269 1522 1 1978.1 4505379H1 1271 1473 1 1978.1 128177676 1348 1957 1 1978.1 g1860340 1388 1801 1 1978.1 g1959763 1438 1931 1 1978.1 160048176 1439 1962 1 1978.1 313710476 1467 1961 1 1978.1 g3231943 1542 1999 1 1978.1 5195075H1 1543 1772 1 1978.1 g3231851 1547 1999 1 1978.1 g3539313 1559 2000 1 1978.1 g3539311 1559 2001 SE6~ Template Component Start Stop ID NO: ID ID

1 1978.1 764088H1 1571 1866 1 1978.1 765817H1 1571 1820 1 1978.1 76581786 1571 1972 1 1978.1 765817T6 1571 1964 1 1978.1 81860995 1588 2012 1 1978.1 84068873 1592 2000 1 1978.1 82787512 1594 2000 1 1978.1 81202822 1605 2000 1 1978.1 g 1425795 1639 2004 1 1978.1 2202630T6 1656 1956 1 1978.1 2202630H1 1664 1911 1 1978.1 2202630F6 1664 1996 1 1978.1 g 1775688 1702 1969 1 1978.1 8714967 1724 2012 1 1978.1 2290116H1 1725 1992 1 1978.1 2127226H1 1725 1998 1 1978.1 3815472H1 1739 2000 1 1978.1 8989478 1752 1987 1 1978.1 83043215 1787 2005 1 1978.1 2413731H1 1868 2004 2 2588.4 3502438H1 2224 2533 2 2588.4 82786213 2248 2674 2 2588.4 83277689 2254 2669 2 2588.4 2366762H1 2248 2486 2 2588.4 1910722H1 2255 2499 2 2588.4 84286541 2256 2664 2 2588.4 83052444 2260 2670 2 2588.4 832051T6 2268 2624 2 2588.4 82873700 2274 2671 2 2588.4 82876032 2276 2668 2 2588.4 2663178H1 2278 2519 2 2588.4 81482457 2282 2670 2 2588.4 2868714H1 2290 2577 2 2588.4 83239166 2301 2671 2 2588.4 83700567 2302 2669 2 2588.4 4595434H1 2361 2549 2 2588.4 g 1118566 2382 2669 2 2588.4 81693563 2384 2670 2 2588.4 81920095 2390 2675 2 2588.4 2370688H1 2416 2519 2 2588.4 g 1952447 2420 2676 2 2588.4 81124041 2428 2669 2 2588.4 8787440 2432 2669 2 2588.4 82322889 2432 2803 2 2588.4 g 1885881 2434 2677 2 2588.4 81267377 2451 2817 2 2588.4 g 1119118 2466 2669 2 2588.4 81218402 2474 2669 2 2588.4 2768580Th 2481 2630 2 2588.4 82102824 2482 2892 SEQ ID Template Component Start Stop NO: ID ID

2 2588.4 1844326H1 2483 2669 2 2588.4 2768580H1 2488 2670 2 2588.4 2768580F6 2488 2670 2 2588.4 82457806 2514 2667 2 2588.4 1854244H1 2530 2669 2 2588.4 1830904Th 2533 2622 2 2588.4 1854244Th 2533 2630 2 2588.4 g 1484958 2560 2670 2 2588.4 35b5846H1 2565 2885 2 2588.4 8845861 2570 2688 2 2588.4 2094b84H1 2574 2669 2 2588.4 4157557H1 2598 2867 2 2588.4 3412843H1 2640 2859 2 2588.4 2467396Th 2734 3206 2 2588.4 2467396Fb 2741 . 3192 2 2588.4 2467396H1 2741 2978 2 2588.4 31486bOH1 2882 2992 2 2588.4 82435914 2884 3178 2 2588.4 2832630F6 2918 3237 2 2588.4 2832b30H1 2918 3174 2 2588.4 2832630Th 2922 3199 2 2588.4 81154518 2999 3296 2 2588.4 8845812 3031 3245 2 2588.4 4118483H1 3044 3213 2 2588.4 g 1123141 3054 3244 2 2588.4 2268209Th 761 1105 2 2588.4 2672328F6 1 357 2 2588.4 2590094H2 1 227 2 2588.4 2b72328H1 1 227 2 2588.4 2672248H1 1 227 2 2588.4 2159193H1 1 149 2 2588.4 2660709H1 5 253 2 2588.4 3046945H1 14 316 2 2588.4 20476b1H1 30 315 2 2588.4 81957845 31 476 2 2588.4 82210487 57 387 2 2588.4 3b98574H1 308 459 2 2588.4 5633547H1 440 637 2 2588.4 2892108H1 440 708 2 2588.4 3496131H1 490 777 2 2588.4 3111455H1 513 783 2 2588.4 2536480H1 550 792 2 2588.4 4971550H1 560 817 2 2588.4 226820986 570 955 2 2588.4 2268209H1 571 833 2 2588.4 1259305F1 611 1189 2 2588.4 3773508H1 612 930 2 2588.4 1259305H1 611 838 2 2588.4 82534bH1 685 983 2 2588.4 212237bH1 702 955 SE6~ Template Component Start Stop ID NO: ID ID

2 2588.4 3108360H1 743 1017 2 2588.4 g2210429 769 1039 2 2588.4 5188115H1 895 1068 2 2588.4 646258H1 907 1068 2 2588.4 4564951H1 961 1217 2 2588.4 661278H1 999 1263 2 2588.4 660712H1 999 1267 2 2588.4 634487H1 987 1238 2 2588.4 82037676 1040 1244 2 2588.4 5035180H1 1074 1347 2 2588.4 66127886 999 1563 2 2588.4 5035211H1 1074 1324 2 2588.4 81523090 1093 1462 2 2588.4 3523389H1 1113 1352 2 2588.4 81192612 1099 1470 2 2588.4 1450413H1 1129 1376 2 2588.4 4346111H1 1138 1389 2 2588.4 4346627H1 1138 1401 2 2588.4 3174422H1 1139 1381 2 2588.4 2645913H1 1158 1420 2 2588.4 4959350H1 1163 1408 2 2588.4 2632516H1 1170 1408 2 2588.4 2995782H1 1187 1446 2 2588.4 81950525 1257 1594 2 2588.4 5501962H1 1295 1527 2 2588.4 2866753H1 1313 1647 2 2588.4 81920346 1372 1779 2 2588.4 g 1950552 1426 1678 2 2588.4 1990742H1 1432 1677 2 2588.4 82102880 1453 1926 2 2588.4 2108316H1 1491 1762 2 2588.4 4323533H1 1493 1761 2 2588.4 2326875H1 1498 1749 2 2588.4 2326664H1 1498 1726 2 2588.4 5117484H1 1534 1793 2 2588.4 1794995H1 1560 1832 2 2588.4 3203064H1 1561 1846 2 2588.4 2406583H1 1576 1709 2 2588.4 4144701H1 1594 1773 2 2588.4 3605515H1 1621 1861 2 2588.4 2715994H1 1641 1885 2 2588.4 3141136H1 1644 1889 2 2588.4 3687001H1 1650 1947 2 2588.4 8900018 1654 1998 2 2588.4 81639521 1672 1916 2 2588.4 2860261H1 1690 1969 2 2588.4 3254658H1 1699 1932 2 2588.4 3095495H1 1712 1995 2 2588.4 2660751H1 1768 2016 2 2588.4 83205186 1804 2094 SE6~ Template Component Start Stop ID NO: ID ID

2 2588.4 1812964H1 1804 2036 2 2588.4 832051H1 1804 2072 2 2588.4 1812964F6 1805 2328 2 2588.4 2900724H1 1812 2115 2 2588.4 1496448H1 1817 2058 2 2588.4 g2912624 1840 2122 2 ' 2588.4 g2879636 1844 2122 2 2588.4 g2191548 1846 2122 2 2588.4 5506884H1 1863 2096 2 2588.4 2203126H1 1903 2157 2 2588.4 4159080H1 1906 2135 2 2588.4 1857148H1 1916 2161 2 2588.4 5099926H1 1925 2212 2 2588.4 g787181 1953 2177 2 2588.4 3327731H1 1983 2283 2 2588.4 5572386H1 1994 2106 2 2588.4 4986441H1 2004 2303 2 2588.4 3110534H1 2004 2279 2 2588.4 5396265T1 2047 2631 2 2588.4 2189071T6 2070 2626 2 2588.4 2189071H1 2072 2357 2 2588.4 2189071F6 2072 2492 2 2588.4 2783063H1 2074 2365 2 2588.4 539637571 2081 2633 2 2588.4 4862535H1 2082 2244 2 2588.4 267232876 2092 2636 2 2588.4 1972459H1 2094 2376 2 2588.4 3786773H1 2114 2409 2 2588.4 66127876 2145 2631 2 2588,4 3994175H 2158 2450 2 2588.4 3995990H1 2160 2411 2 2588.4 5137950H2 2208 2487 2 2588,4 g1523038 2213 2669 2 2588.4 2664705H1 2212 2338 2 2588.4 g3308729 2218 2673 3 201759.3 83662481 823 1315 3 201759,3 039821H1 861 1031 3 201759.3 5278457H1 871 1132 3 201759.3 836624H1 872 1143 3 201759.3 836632H1 873 1140 3 201759.3 4299787H1 879 1057 3 201759.3 263784H1 898 1265 3 201759.3 g2017411 900 1347 3 201759.3 82619981 904 1553 3 201759.3 826199H1 904 1190 3 201759,3 g1463426 908 1456 3 201759.3 2011073H1 914 1130 3 201759.3 4203594H1 917 1203 3 201759.3 2021844H1 918 1180 3 201759.3 4861150H1 919 1199 b2 SEQ ID Template Component Starf Stop NO: ID ID

3 201759.3 1494424H1 958 1173 3 201759.3 3697752H1 970 1290 3 201759.3 81049651 984 1332 3 201759.3 3015055H1 987 1320 3 201759.3 1857956H1 990 1165 3 201759.3 1857956F6 990 1530 3 201759.3 5112648H1 997 1334 3 201759.3 535858H1 1000 1099 3 201759.3 5091726H1 1015 1322 3 201759.3 1952952H1 1015 1309 3 201759.3 1257476H1 1016 1281 3 201759.3 4585955H1 1017 1309 3 201759.3 5836690H1 1018 1270 3 201759.3 4648947H1 1027 1197 3 201759.3 958699H1 1029 1339 3 201759.3 3960850H2 1028 1325 3 201759.3 691887H1 1030 1258 3 201759.3 g 1240155 1040 1284 3 201759.3 81025462 1053 1335 3 201759.3 g 1264434 1053 1450 3 201759.3 3354080H1 1065 1243 3 201759.3 8863516 1067 1324 3 201759.3 5428281H1 1073 1362 3 201759.3 1236418H1 1075 1290 3 201759.3 3525638H1 1085 1444 3 201759.3 4086966H1 1102 1398 3 201759,3 2921953H1 1116 1433 3 201759.3 2370849H1 1117 1402 3 201759.3 1649210H1 1117 1383 3 201759.3 4159589H1 1126 1416 3 201759.3 83919705 1134 1658 3 201759.3 2840735H1 1139 1417 3 201759.3 1401895H1 1140 1414 3 201759,3 82110825 1140 1652 3 201759.3 3807071H1 1141 1491 3 201759,3 4112417H1 1144 1251 3 201759.3 3843828H1 1143 1465 3 201759.3 83238572 1144 1668 3 201759.3 82347672 1147 1665 3 201759,3 82930046 1147 1665 3 201759,3 83238573 1150 1668 3 201759.3 82742072 1171 1658 3 201759.3 83595471 1176 1658 3 201759.3 83988715 1176 1658 3 201759.3 83644962 1177 1668 3 201759.3 3466714H1 1177 1467 3 201759.3 81384561 1180 1673 3 201759.3 83446683 1181 1670 3 201759.3 83679958 1184 1664 3 201759.3 g 13321 1190 1663 b5 b3 SE6~ Template Component Start Stop ID NO: ID ID

3 201759.3 3600088H1 1200 1528 3 201759.3 2542561T6 1207 1633 3 201759.3 900346H1 1225 1325 3 201759.3 90034681 1225 1658 3 201759.3 8848629 1225 1571 3 201759.3 5056168H1 1225 1530 3 201759.3 3112117H1 1233 1546 3 201759.3 82524963 1240 1658 3 201759.3 84332204 1241 1665 3 201759.3 3366929H1 1244 1517 3 201759.3 83432662 1244 1666 3 201759,3 82806722 1246 1661 3 201759.3 83931304 1247 1667 3 201759.3 83601403 1248 1663 3 201759.3 83238932 1252 1665 3 201759.3 83931309 1258 1667 3 201759.3 2293916H1 1261 1529 3 201759.3 2399275H1 1272 1541 3 201759.3 82557656 1281 1663 3 201759.3 82617892 1281 1659 3 201759.3 82463986 1286 1668 3 201759.3 82457535 1288 1646 3 201759.3 83416543 1292 1643 3 201759.3 83095258 1297 1665 3 201759.3 82669541 1297 1658 3 201759.3 3467486H1 1311 1579 3 201759.3 82198192 1314 1665 3 201759.3 g 749662 1313 1659 3 201759.3 8752157 1313 1580 3 201759.3 82188331 1324 1670 3 201759.3 83308655 1325 1658 3 201759.3 82156163 1331 1835 3 201759.3 83229304 1342 1668 3 201759.3 82969733 1349 1665 3 201759.3 2664494Th 1352 1622 3 201759.3 81049959 1369 1670 3 201759.3 82243211 1366 1668 3 201759.3 8863517 1371 1642 3 201759.3 8784617 1372 1665 3 201759.3 81614677 1368 1658 3 201759.3 84148476 1369 1665 3 201759.3 81294977 1369 1658 3 201759.3 82955119 1373 1667 3 201759.3 81448860 1373 1658 3 201759.3 g 29581 1395 1658 b 1 3 201759.3 83233016 1401 1663 3 201759.3 4640182H1 1401 1660 3 201759.3 83884622 1404 1670 3 201759.3 83431226 1406 1658 3 201759.3 83843156 1407 1658 b4 SEQ ID Template Component ~ Start Stop NO: ID ID

3 201759.3 2101118H1 1413 1655 3 201759.3 2044357H1 1428 1688 3 201759.3 3573519Th 1432 1996 3 201759.3 1695963T6 1432 1995 3 201759.3 2351137H1 1458 1662 3 201759.3 1901951H1 1468 1763 3 201759.3 2505488H2 1468 1721 3 201759.3 2052204H1 1486 1761 3 201759.3 2016130H1 1 95 3 201759.3 5373386H1 24 184 3 201759.3 6026840H1 51 139 3 201759.3 2598924H1 87 375 3 201759.3 2598924F6 88 598 3 201759.3 1318607H1 88 321 3 201759.3 3450621H1 93 257 3 201759.3 2664494H1 96 332 3 201759.3 2664494F6 96 652 3 201759.3 3573519F6 98 681 3 201759.3 3573519H1 98 405 3 201759.3 4177617H1 102 371 3 201759.3 4920283H1 101 194 3 201759.3 4843441H1 104 378 3 201759.3 3069036H1 104 395 3 201759.3 3374007H1 109 376 3 201759.3 4662762H1 109 366 3 201759.3 2160985H1 109 364 3 201759.3 2964373H1 109 423 3 201759,3 3561542H1 110 405 3 201759.3 3579440H1 110 414 3 201759.3 1571030H1 110 302 3 201759.3 3595416H1 112 234 3 201759.3 2133581H1 113 395 3 201759.3 3281108H1 112 376 3 201759.3 3658478H1 112 394 3 201759.3 3359378H1 117 395 3 201759.3 g1962636 119 523 3 201759.3 3373501H1 119 374 3 201759,3 899120H1 123 209 3 201759.3 2913242H1 123 383 3 201759.3 4974963H1 123 215 3 201759.3 81813092 125 514 3 201759.3 1531710H1 126 327 3 201759.3 4270743H1 163 428 3 201759.3 4522315H1 170 429 3 201759.3 2647741H1 176 428 3 201759.3 3031088H1 194 497 3 201759,3 82163335 192 565 3 201759.3 3895133H1 205 527 3 201759,3 3950958H1 272 434 3 201759,3 5538554H2 305 502 b5 SEQ ID Template Component Start Stop NO: ID ID

3 201759.3 1911718H1 323 482 3 201759.3 g4084676 346 828 3 201759.3 5713320H1 362 659 3 201759.3 583652bH1 363 651 3 201759.3 5833621H1 3b3 651 3 201759.3 2858391H1 367 b31 3 201759.3 2859193H1 367 b22 3 201759.3 g2255078 377 819 3 201759.3 273057bH1 423 698 3 ~ 201759.3 1695963Fb 433 907 3 201759.3 4548b39H1 433 676 3 201759.3 2674195H1 433 678 3 201759.3 1695963H1 433 685 3 201759.3 g21 b317b 461 890 3 201759.3 3422493H1 470 700 3 201759.3 597747H1 475 712 3 201759.3 436190H1 489 747 3 201759.3 g761512 496 878 3 201759.3 g 1799100 496 1022 3 201759.3 1707486H1 506 730 3 201759.3 3758616H1 511 639 3 201759.3 173498H1 523 720 3 201759.3 g883464 549 959 3 201759,3 4299747H1 566 794 3 201759.3 4301171H1 5bb 775 3 201759.3 g788509 576 853 3 201759.3 39b857bH1 586 911 3 201759.3 173498F1 593 1035 3 201759.3 3624367H1 611 886 3 201759.3 5811130H1 618 916 3 201759.3 2480172H1 620 957 3 201759.3 3233075H1 626 934 3 201759.3 1376454H1 629 872 3 201759.3 1376454F1 629 1103 3 201759.3 4824995H1 633 903 3 201759,3 1611033H1 638 856 3 201759.3 1b110b4H1 638 840 3 201759.3 85064981 639 1297 3 201759.3 850b49H1 639 901 3 201759,3 280397H1 640 1029 3 201759.3 3608679H1 639 848 3 201759.3 3502463H1 644 9bb 3 201759.3 4302480H1 646 950 3 201759.3 166390H1 652 925 3 201759,3 465154H1 675 922 3 201759,3 2471187H1 696 946 3 201759.3 81332164 698 1205 3 201759.3 81988555 704 1008 3 201759.3 167885H1 704 1055 3 201759.3 167849H1 705 1059 bb SE6~ Template Component Start Stop ID NO: ID ID

3 201759.3 087337H1 707 954 3 201759.3 1482767H1 724 988 3 201759.3 81614676 733 862 3 201759.3 8874674 740 1147 3 201759.3 8877795 740 1099 3 201759.3 668420H1 739 986 3 201759.3 061003H1 741 915 3 201759.3 81448859 753 1297 3 201759.3 5861969H1 754 1038 3 201759.3 2961324H1 754 1072 3 201759.3 2545528H1 760 1023 3 201759.3 030800H1 761 1060 3 201759.3 3599778H1 779 1014 3 201759.3 4886074H1 790 1073 3 201759.3 2702328H1 790 1054 3 201759.3 4724311H1 797 910 3 201759.3 1674833H1 802 1024 3 201759.3 81055891 803 1147 3 201759.3 4425751H1 817 1097 3 201759.3 700809H1 819 1111 3 201759.3 700858H1 819 1108 3 201759,3 81406784 1492 1915 3 201759.3 83307726 1501 1658 3 201759.3 83405773 1505 1969 3 201759.3 1007491H1 1541 1848 3 201759.3 83841579 1547 1665 3 201759.3 5906115H1 1549 1665 3 201759.3 83016169 1550 1658 3 201759.3 82967986 1558 1658 3 201759.3 1416494H1 1560 1811 3 201759.3 2111952H1 1560 1859 3 201759.3 82265647 1572 2043 3 201759.3 82106597 1571 1674 3 201759.3 040426H1 1577 1834 3 201759.3 8314936 1600 2038 3 201759.3 83872004 1609 2038 3 201759.3 82112437 1613 2047 3 201759.3 81382965 1616 2039 3 201759.3 82930234 1617 2039 3 201759.3 82559360 1619 2038 3 201759.3 1602514Th 1630 1972 3 201759.3 5022224H1 1637 1919 3 201759.3 1602514F6 1638 1821 3 201759.3 1602514H1 1638 1841 3 201759.3 g 1813014 1642 2039 3 201759.3 82107167 1647 2047 3 201759.3 1857956T6 1653 2000 3 201759.3 83770498 1655 2040 3 201759.3 8518019 1702 2038 3 201759.3 8883358 1708 2046 SEQ ID Template Component Start Stop NO: ID ID

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12 241236.3 g2273603 1701 2012 12 241236.3 2989623T6 1740 1966 12 241236.3 2625824H1 1750 1989 12 241236.3 2625824Th 1758 1956 12 241236.3 2625824F6 1750 2010 12 241236.3 g3756824 1 393 12 241236.3 5376769H1 1 249 12 241236.3 3473825H1 115 374 12 241236.3 1675287H1 134 303 12 241236.3 1675845H1 135 314 12 241236.3 2047281F6 271 810 12 241236.3 2047281H1 271 482 12 241236.3 3724339H1 352 632 12 241236.3 5733241H1 404 664 12 241236,3 4909488H1 408 664 12 241236.3 1857844H1 412 667 12 241236.3 3078885H1 467 776 12 241236.3 4883514F6 529 963 12 241236.3 4883514H1 529 815 12 241236.3 g1023658 566 798 12 241236.3 1222879H1 644 871 12 241236.3 3400427H1 661 890 12 241236.3 1702383H1 664 880 12 241236.3 4902281H1 687 953 12 241236.3 4380777H1 697 956 12 241236.3 868686H1 702 954 12 241236.3 2598561H1 706 994 12 241236.3 3672519H1 718 995 12 241236.3 5811931H1 729 1048 12 241236.3 4863967H 7b9 1059 12 241236.3 1534650H1 780 979 12 241236.3 4852733H1 780 1034 12 241236.3 1532438H1 780 987 12 241236.3 3407892H1 791 1049 12 241236,3 4173535H1 841 1129 12 241236.3 736762H1 845 1073 12 241236.3 987503H1 867 1107 12 241236,3 3591339H1 899 1203 12 241236.3 1600224H1 907 1096 12 241236,3 1680682H1 924 1117 12 241236.3 98487681 967 1431 12 241236.3 5022045H1 967 1235 12 241236.3 984876H1 967 1272 12 241236.3 2394790H1 995 1238 12 241236.3 3105586H1 1029 1318 12 241236.3 2116090H1 1029 1295 12 241236.3 g3894545 1045 1441 12 241236.3 1665126H1 1048 1280 12 241236.3 2812429H1 1096 1416 12 241236.3 3099677H1 1102 1419 SEQ ID Template Component Start Stop NO; ID ID

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12 241236.3 3014105H1 1509 1829 12 241236,3 1994356H1 1513 1799 12 241236.3 5568339H1 1525 1765 12 241236,3 3186679H1 1537 1873 12 241236,3 4828122H1 1544 1837 12 241236.3 4828623H1 1544 1807 12 241236.3 g3595120 1549 2018 12 241236,3 g2177775 1559 2016 12 241236,3 1456253H1 1562 1841 12 241236.3 1000028H1 1564 1808 12 241236.3 3791315H1 1567 1881 12 241236.3 g4392232 1568 2013 12 241236.3 g2968124 1767 2016 SEQ ID Template Component Start Stop NO: ID ID

12 241236.3 4115186H1 1773 2017 12 241236.3 3392646H1 1783 2058 12 241236.3 g3239075 1838 2014 12 241236.3 g3808002 1848 2016 12 241236.3 84072387 1848 2014 12 241236.3 3781961H1 1848 2169 12 241236.3 83754629 1851 2016 12 241236.3 84006032 1860 2015 12 241236.3 84073569 1860 2010 12 241236.3 84005900 1870 2007 12 241236.3 83321490 1862 2009 12 241236.3 84006303 1870 2007 12 241236.3 84087154 1871 2010 12 241236.3 83862359 1871 2010 12 241236.3 83322077 1862 2015 12 241236.3 84005537 1871 2010 12 241236.3 83846653 1871 2010 12 241236.3 84077466 1862 2010 12 241236.3 84080249 1871 2011 12 241236.3 83862436 1871 2010 12 241236.3 84018950 1863 2007 12 241236.3 84077665 1871 2010 12 241236.3 83989227 1871 2010 12 241236.3 83806894 1864 2014 12 241236.3 83932638 1871 2011 12 241236.3 83862447 1871 2010 12 241236.3 83847853 1871 2010 12 241236.3 83989984 1871 2010 12 241236.3 83890144 1871 2011 12 241236.3 83989001 1871 2010 12 241236.3 84071839 1871 2008 12 241236.3 83847054 1871 2008 12 241236.3 83989318 1871 2016 12 241236.3 83890413 1871 2016 12 241236.3 83848056 1871 2007 12 241236.3 84282452 1871 2007 12 241236.3 84018579 1871 2014 12 241236.3 83990148 1871 2014 12 241236.3 83890229 1871 2010 12 241236.3 83847713 1871 2010 12 241236.3 504961H1 1872 2018 12 241236.3 2475277H1 1872 2017 12 241236.3 83149294 1964 ~ 2016 13 245014.1 168004H1 1773 2112 13 245014.1 16800486 1777 2032 13 245014.1 3444984H1 1854 2115 13 245014.1 963645H1 1859 2101 13 245014.1 96364582 1859 2354 13 245014.1 83095484 1869 1985 13 245014.1 2278942H1 1903 2171 SEQ ID Template Component Start Stop NO: ID ID

13 245014.1 3993577H1 1907 2200 13 245014.1 3518094H1 1918 2179 13 245014.1 5696350H1 1918 2173 13 245014.1 4507976H1 1924 2192 13 245014.1 3020932H1 1924 2204 13 245014.1 4400157H1 1949 2191 13 245014.1 3248110H1 1949 2229 13 245014.1 2855006H1 1949 2041 13 245014.1 5399133H1 1 213 13 245014.1 345036186 68 543 13 245014.1 3450361H1 68 327 13 245014.1 2731452F6 81 421 13 245014.1 2731452H1 81 320 13 245014.1 263691H1 94 428 13 245014.1 5674201H1 106 347 13 245014.1 2645021H1 207 460 13 245014.1 8895569 346 512 13 245014.1 1923470Th 2455 2704 13 245014.1 192347086 2469 2742 13 245014.1 1923470H1 2469 2740 13 245014.1 81874511 2471 2748 13 245014.1 83179513 2407 2746 13 245014.1 g 1153232 241 b 2748 13 245014.1 2285748H1 2426 2679 13 245014.1 2875652H1 2477 2743 13 245014.1 8878521 2504 2740 13 245014.1 82810267 2508 2751 13 245014.1 84457618 2512 2745 13 245014.1 186006176 2430 2701 13 245014.1 1636359H1 2527 2620 13 245014.1 974331H1 2439 2619 13 245014.1 81548974 2445 2740 13 245014.1 4802874H1 2527 2633 13 245014.1 2785026H1 2528 2716 13 245014.1 82209561 2448 2743 13 245014.1 2862743H1 2558 2742 13 245014.1 82208300 2452 2740 13 245014.1 82987537 2624 2751 13 245014.1 3318766H1 1684 1957 13 245014.1 4825016H1 1699 1982 13 245014.1 3776745H1 1732 2032 13 245014.1 4368674H1 1746 2008 13 245014.1 2650579H1 1749 1945 13 245014.1 5062862H1 1764 2021 13 245014.1 5062961H2 1766 2004 13 245014.1 4089945H1 1770 1847 13 245014.1 263180276 2246 2706 13 245014.1 4863733H1 2264 2562 13 245014.1 5328806H1 2261 2544 13 245014.1 83917411 2269 2748 SEQ ID Template Component Start Stop NO. ID ID

13 245014.1 82838934 2255 2747 13 245014.1 3166548H1 2273 2559 13 245014.1 82818702 2280 2690 13 245014.1 83693781 2261 2742 13 245014.1 81068825 2306 2659 13 245014.1 83016160 2306 2749 13 245014.1 607473H1 2309 2584 13 245014.1 3558364H1 2329 2637 13 245014.1 84329144 2346 2738 13 245014.1 81941347 2347 2733 13 245014.1 4302681H1 2356 2591 13 245014.1 83182104 2369 2745 13 245014.1 1299474Th 2371 2705 13 245014.1 1299474F6 2377 2742 13 245014.1 82003283 2377 2742 13 245014.1 1302005H1 2380 2722 13 245014.1 81219422 2396 2743 13 245014.1 178082H1 1590 1829 13 245014.1 064892H1 1591 1750 13 245014.1 963385H1 1595 1896 13 245014.1 96338582 1595 1972 13 245014.1 81068873 1463 1775 13 245014.1 2280635H1 1470 1750 13 245014.1 14562381 1453 1886 13 245014.1 960167H1 1546 1671 13 245014.1 81166309 1456 1851 13 245014.1 3638263H1 1553 1845 13 245014.1 5423560H1 1615 1861 13 245014.1 1495185H1 1633 1857 13 245014.1 82209742 1636 2103 13 245014.1 927457H1 1650 1930 13 245014.1 722266H1 1650 1917 13 245014.1 929020H1 1650 1913 13 245014.1 92745781 1650 2180 13 245014.1 81874627 1666 1896 13 245014.1 81920695 1632 1830 13 245014.1 637604H1 1672 1906 13 245014.1 81958169 1678 1988 13 245014.1 8959179 1452 1761 13 245014.1 3038691H1 1453 1545 13 245014.1 3398816H1 1453 1567 13 245014.1 4212104H1 937 1209 13 245014.1 5500792H1 976 1201 13 245014.1 6012320H1 996 1270 13 245014.1 2675268H1 1000 1244 13 245014.1 2675268F6 1000 1405 13 245014.1 3724087H1 1035 1309 13 245014.1 3069566H1 1096 1395 13 245014.1 5508358H1 1126 1346 13 245014.1 5592345H1 1278 1487 SEQ ID Template Component Start Stop NO: ID ID

13 245014.1 141058H1 1278 1534 13 245014,1 3714983H1 1373 1661 13 245014.1 3515644H1 1417 1647 13 245014.1 4797535H1 360 650 13 245014.1 81128352 373 613 13 245014.1 82003284 456 712 13 245014.1 4164512H1 367 675 13 245014.1 8878573 547 871 13 245014.1 2749018H1 576 825 13 245014.1 3450361T6 593 1156 13 245014.1 2910268H1 610 873 13 245014.1 4372565H1 613 915 13 245014.1 133005H1 618 801 13 245014.1 13300586 618 1056 13 245014.1 4972429H1 693 985 13 245014.1 4435621H1 735 1012 13 245014.1 83446618 746 1207 13 245014.1 3275925H1 745 986 13 245014.1 5299476H1 746 899 13 245014.1 82541414 754 1204 13 245014,1 3629224H1 1987 2293 13 245014.1 160092H1 2017 2421 13 245014.1 3256601H1 2029 2284 13 245014.1 5091829H1 1988 2256 13 245014.1 3489772H1 2057 2357 13 245014.1 82057259 2087 2423 13 245014,1 8395755 2096 2414 13 245014.1 218809H1 2112 2381 13 245014.1 3493510H1 2011 2285 13 245014.1 217964H1 2112 2345 13 245014.1 1376993F1 2115 2581 13 245014.1 1376993H1 2115 2356 13 245014.1 113469H1 2014 2268 13 245014.1 1860061F6 2124 2549 13 245014.1 1860061H1 2124 2428 13 245014.1 3806342H1 2014 2255 13 245014.1 828638H1 2137 2406 13 245014,1 82863881 2137 2607 13 245014.1 5710216H2 2171 2422 13 245014,1 344609H1 2015 2226 13 245014.1 4121876H1 2174 2394 13 245014,1 4416742H1 2176 2434 13 245014.1 133005Th 2176 2707 13 245014,1 145623F1 2183 2740 13 245014,1 5500510H1 2192 2451 13 245014,1 82444538 2195 2559 13 245014.1 82163904 2198 2658 13 245014.1 004038H1 2203 2582 13 245014.1 003770H1 2203 2566 13 245014.1 003808H1 2203 2532 SE6~ Template Component Start Stop ID NO: ID ID

13 245014.1 4356958H1 2221 2498 13 245014,1 168004Th 2222 2703 13 245014.1 3858354H1 2235 2426 13 245014.1 3858174H1 2236 2531 13 245014.1 4602871H1 768 1018 13 245014.1 2884645H1 776 1041 13 245014.1 4196193H1 873 1007 13 245014.1 g2139409 887 1282 13 245014.1 2872604H1 890 1150 13 245014.1 4548678H1 890 1121 13 245014.1 g 1953042 915 11 b5 13 245014.1 3438285H1 1440 1656 13 245014.1 2462626H1 1448 1680 13 245014.1 3491523H1 1440 1685 14 245251.6 g3806445 1422 1590 14 245251.6 g3806467 1422 1590 14 245251,6 g3848606 1422 1590 14 245251.6 g3849478 1422 1590 14 245251.6 g3845826 1422 1590 14 245251.6 g3806471 1422 1590 14 245251.6 g3846603 1422 1590 14 245251.6 g4034496 1422 1594 14 245251.6 g3807003 1422 1591 14 245251.6 g3806382 1422 1593 14 245251.6 83847027 1422 1587 14 245251.6 83989330 1422 1587 14 245251.6 83861794 1422 1587 14 245251.6 84018012 1422 1593 14 245251.6 83847094 1422 1591 14 245251.6 83807437 1422 1593 14 245251.6 83846856 1422 1592 14 245251.6 84284777 1422 1586 14 245251.6 83847587 1422 1593 14 245251,6 84186360 1422 1593 14 245251.6 83990433 1422 1593 14 245251.6 83807539 1422 1593 14 245251,6 83990700 1422 1593 14 245251.6 84071417 1422 1593 ~

14 245251.6 83806276 1422 1592 14 245251,6 83806906 1422 1592 14 245251,6 83847511 1422 1592 14 245251,6 83842268 1422 1593 14 245251.6 83846164 1422 1592 14 245251.6 83846151 1422 1592 14 245251,6 84077836 1422 1594 14 245251.6 83862401 1422 1593 14 245251.6 84082235 1422 1593 14 245251.6 83847852 1422 1593 14 245251.6 83842306 1422 1591 14 245251.6 84074675 1422 1591 SE6~ Template Component Start Stop ID NO: ID ID

14 245251.6 83861509 1422 1593 14 245251.6 83989299 1422 1593 14 245251.6 84074633 1422 1591 14 245251.6 83848075 1422 1593 14 245251,6 83847601 1422 1596 14 245251.6 83846659 1422 1591 14 245251.6 83807971 1422 1593 14 245251.6 83862373 1422 1592 14 245251.6 83846613 1422 1594 14 245251.6 83842371 1422 1593 14 245251.6 84150319 1422 1593 14 245251.6 83848195 1422 1593 14 245251.6 84186335 1422 1593 14 245251.6 84071420 1422 1590 14 245251.6 83845843 1422 1590 14 245251.6 271945H1 1423 1592 14 245251.6 4860092H1 1425 1549 14 245251.6 3025205H1 1425 1591 14 245251.6 81329015 1110 1592 14 245251.6 1708907H1 1110 1392 14 245251,6 2356035H1 1113 1395 14 245251.6 83321637 1412 1593 14 245251.6 83321397 1412 1591 14 245251.6 83990361 1412 1594 14 245251.6 83321297 1412 1594 14 245251.6 83321613 1412 1590 14 245251.6 83321619 1412 1590 14 245251,6 83321346 1412 1590 14 245251,6 83321642 1412 1592 14 245251,6 83322073 1412 1593 14 245251,6 83322037 1412 1579 14 245251,6 83321904 1412 1591 14 245251.6 83322057 1412 1594 14 245251,6 84086504 1412 1593 14 245251.6 83321689 1412 1593 14 245251.6 83322072 1412 1594 14 245251.6 290509H1 1413 1593 14 245251.6 83842429 1413 1595 14 245251.6 83321374 141 b 1590 14 245251.6 2715779H1 1417 1590 14 245251.6 83841465 1420 1590 14 245251.6 83847930 1421 1590 14 245251.6 83847580 1421 1592 14 245251.6 84187012 1421 1590 14 245251.6 83806657 1421 1586 14 245251.6 83846129 1421 1590 14 245251.6 84005749 1421 1592 14 245251.6 84005487 1421 1590 14 245251.6 83665836 1422 1590 14 245251.6 83848560 1422 1590 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 83845838 1422 1590 14 245251.6 83848559 1422 1590 14 245251.6 703105H1 1113 1417 14 245251.6 81501582 1117 1592 14 245251.6 83255080 1119 1602 14 245251.6 84081903 1119 1598 14 245251.6 81948394 1156 1590 14 245251.6 2411955H1 1117 1414 14 245251.6 4569146H1 1120 1459 14 245251.6 027069H1 1165 1412 14 245251.6 1538171H1 1120 1407 14 245251.6 83279555 1127 1593 14 245251.6 84114349 1128 1594 14 245251.6 83740354 1131 1592 14 245251.6 82279150 1132 1590 14 245251.6 84533152 1132 1592 14 245251.6 83962173 1132 1596 14 245251.6 887316H1 1138 1466 14 245251.6 82397876 1165 1592 14 245251.6 82360627 1138 1598 14 245251.6 82714133 1137 1590 14 245251.6 83016485 1165 1596 14 245251.6 82464368 1139 1594 14 245251.6 82552766 1146 1590 14 245251.6 2962133H1 1150 1496 14 245251.6 82464621 1152 1589 14 245251.6 537878H1 1150 1446 14 245251.6 1359957H1 1148 1419 14 245251.6 1963987H1 1155 1496 14 245251.6 83253832 1165 1593 14 245251.6 82913751 1168 1593 14 245251.6 82932949 1173 1602 14 245251.6 83735276 1178 1602 14 245251.6 863137H1 1181 1466 14 245251.6 84269459 1181 1590 14 245251.6 82563609 1183 1590 14 245251.6 2418779H1 1185 1471 14 245251.6 84113654 1188 1590 14 245251.6 81641703 1188 1586 14 245251.6 1551309H1 1190 1448 14 245251.6 83840122 1192 1597 14 245251.6 82705424 1200 1589 14 245251.6 2286469H1 1200 1498 14 245251.6 82566862 1209 1593 14 245251.6 82435745 1212 1361 14 245251.6 2088012H1 1215 1517 14 245251.6 1312225H1 1215 1472 14 245251.6 82270163 1215 1592 14 245251.6 2288870H1 1215 1497 14 245251.6 8864236 1220 1591 SE6~ Template Component Start Stop ID NO: ID ID

14 245251.6 83597473 1220 1598 14 245251.6 81972695 1223 1595 14 245251.6 83322133 1231 1594 14 245251.6 81148477 1231 1598 14 245251.6 83960762 1244 1590 14 245251.6 272932H1 1248 1590 14 245251.6 3334564H1 1248 1581 14 245251.6 1355971H1 1248 1540 14 245251.6 1907330H1 1248 1548 14 245251.6 81774782 1253 ~ 1594 14 . 245251.6 8927896 1244 1592 14 245251.6 82279391 1256 1596 14 245251.6 83280855 1259 1597 14 245251.6 981518H1 1265 1598 14 245251.6 83070488 1267 1596 14 245251.6 84269675 1271 1593 14 245251.6 83127594 1273 1545 14 245251.6 84297922 1273 1593 14 245251.6 81527256 1274 1590 14 245251.6 83215022 1273 1593 14 245251.6 81927427 1278 1590 14 245251.6 81618008 1279 1599 14 245251.6 8651970 1270 1597 14 245251,6 1926049H1 1279 1543 14 245251.6 82053209 1281 1601 14 245251.6 770417H1 1425 1593 14 245251.6 83321693 1426 1590 14 245251.6 544220H1 1464 1596 14 245251.6 83886402 1465 1859 14 245251.6 422119H1 1493 1594 14 245251.6 4832225H1 721 877 14 245251.6 063120H1 727 876 14 245251,6 3228413H1 720 863 14 245251.6 81927545 717 883 14 245251.6 1255835H1 754 894 14 245251,6 3226250H1 699 837 14 245251,6 4323801H1 746 909 14 245251,6 4510868H1 704 796 14 245251.6 4800865H1 700 891 14 245251.6 3715312H1 697 900 14 245251.6 1428725H1 696 883 14 245251.6 2106521H1 480 642 14 245251.6 5100266H1 695 785 14 245251.6 1222560H1 693 907 14 245251.6 360061H1 701 914 14 245251.6 2388047H1 692 901 14 245251.6 81527303 817 919 14 245251.6 1708351H1 699 916 14 245251.6 4563631H1 839 920 14 245251.6 4337368H1 720 919 SEQ ID Template Component Start Stop NO; ID ID

14 245251.6 3284155H1 811 915 14 245251.6 1573816H1 427 644 14 245251.6 g2017060 687 914 14 245251.6 g2992991 687 808 14 245251.6 5945233H1 692 816 14 245251.6 142800H1 686 921 14 245251.6 1611073H1 686 892 14 245251.6 1612960H1 686 871 14 245251,6 5182909H1 686 922 14 245251.6 4675087H1 686 868 14 245251.6 2175031H1 686 917 14 245251.6 1674874H1 686 901 14 245251.6 748598H1 699 925 14 245251.6 g698473 1 375 14 245251.6 g2750955 3 322 14 245251.6 4711779H1 41 296 14 245251.6 2468527H1 173 531 14 245251.6 3674073H1 243 527 14 245251.6 g2015374 251 676 14 245251.6 4710904H1 283 582 14 245251.6 3674243H1 289 527 14 245251,6 5112393H1 314 606 14 245251.6 1960508H1 317 627 14 245251,6 4043372H1 322 607 14 245251.6 2017147H1 341 444 14 245251,6 1725960H1 376 , 592 14 245251,6 1573484H1 377 596 14 245251.6 310542H1 382 643 14 245251.6 3205850H1 400 693 14 245251.6 1726232H1 403 592 14 245251.6 310938H1 407 646 14 245251.6 1877685H1 417 704 14 245251.6 2598596H1 416 704 14 245251.6 3090278H1 416 704 14 245251.6 4128553H1 426 699 14 245251,6 g2030260 426 715 14 245251.6 5538163H1 448 647 14 245251.6 2502707H1 450 699 14 245251.6 1800655H1 462 705 14 245251.6 4899818H1 465 705 14 245251.6 3858619H1 464 724 14 245251.6 2111517H1 478 729 14 245251.6 310488H1 476 642 14 245251.6 1686443H1 491 731 14 245251.6 1425427H1 584 837 14 245251.6 1490475H1 584 812 14 245251.6 4853210H1 586 806 14 245251.6 g3846065 1396 1590 14 245251.6 g4304887 1396 1593 14 245251.6 g4006580 1396 1590 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 84085914 1396 1590 14 245251.6 84005760 1396 1592 14 245251,6 83931547 1396 1593 14 245251.6 83842208 1396 1590 14 245251.6 84082237 1399 1590 14 245251.6 83848014 1403 1590 14 245251.6 83322137 1406 1590 14 245251.6 83883898 1407 1587 14 245251.6 84086951 1407 1590 14 245251.6 84033921 1408 1590 14 245251.6 84077315 1409 1590 14 245251.6 83849422 1409 1587 14 245251.6 83322163 1409 1590 14 245251.6 84005466 1410 1596 14 245251.6 84189675 1409 1587 14 245251.6 83842222 1410 1593 14 245251.6 84073579 1410 1593 14 245251.6 84071991 1410 1593 14 245251.6 83848782 1410 1590 14 245251.6 83842461 1410 1590 14 245251.6 83890086 1410 1589 14 245251.6 84073751 1410 1587 14 245251.6 84072155 1410 1587 14 245251.6 84005762 1410 1587 14 245251.6 84017767 1410 1586 14 245251.6 84082225 1410 1633 14 245251.6 84150699 1410 1587 14 245251.6 83849075 1410 1590 14 245251.6 83842220 1410 1590 14 245251,6 84034488 1410 1592 14 245251,6 84018592 1410 1590 14 245251.6 84071488 1410 1590 14 245251,6 83990408 1410 1584 14 245251.6 84006140 1410 1587 14 245251,6 84148813 1410 1592 14 245251.6 83665905 1410 1591 14 245251.6 84189666 1410 1586 14 245251.6 83842450 1410 1590 14 245251.6 84006752 1410 1593 14 245251.6 83665891 1410 1595 14 245251.6 83848888 1410 1590 14 245251.6 84393782 1410 1590 14 245251.6 83927687 1410 1594 14 245251.6 83931504 1410 1589 14 245251.6 83922922 1411 1589 14 245251.6 83321965 1412 1590 14 245251.6 83321608 1412 1591 14 245251.6 83321192 1412 1590 14 245251.6 83321212 1412 1593 14 245251.6 83848884 1412 1631 SE6~ Template Component Start Stop ID NO: ID ID

14 245251.6 83321780 1412 1590 14 245251.6 83321859 1412 1590 14 245251.6 83322187 1412 1596 14 245251,6 83846123 1412 1587 14 245251.6 83321441 1412 1590 14 245251.6 83322011 1412 1591 14 245251.6 83754224 1049 1606 14 245251,6 83425292 1050 1595 14 245251.6 4996361H1 1014 1361 14 245251.6 4546463H1 1019 1337 14 245251,6 83117255 1018 1545 14 245251.6 82357822 1020 1592 14 245251,6 1853257H1 1021 1384 14 245251.6 g 1722623 1022 1593 .

14 245251.6 82566601 1026 1486 14 245251,6 81328830 1031 1601 14 245251.6 82824176 1029 1592 14 245251.6 84124629 1041 1595 14 245251,6 82269348 1044 1592 14 245251.6 84217707 1045 1593 14 245251.6 84070671 1048 1601 14 245251.6 2240628H1 1047 1379 14 245251.6 84524298 3 185 14 245251.6 84005797 8 142 14 245251.6 813528H1 686 905 14 245251.6 83807474 1283 1416 14 245251.6 84327570 1238 1419 14, 245251.6 1645004H1 451 672 14 245251.6 1312584H1 697 963 14 245251.6 3471164H1 720 993 14 245251.6 4998559H1 722 1004 14 245251.6 83890267 1283 1418 14 245251.6 4351329H1 686 824 14 245251.6 1672134H1 1233 1423 14 245251.6 83848850 1283 1415 14 245251.6 1517530H1 462 672 14 245251,6 82037443 332 608 14 245251.6 3315274H1 739 996 14 245251.6 83990415 1283 1419 14 245251.6 83849121 1283 1415 14 245251.6 3272177H1 680 917 14 245251.6 5913406H1 686 954 14 245251.6 83848236 1283 1417 14 245251.6 052757H1 756 994 14 245251.6 4708284H1 686 930 14 245251.6 83848935 1283 1416 14 245251.6 83890340 8 142 14 245251.6 82025954 684 995 14 245251.6 1990122H1 581 672 14 245251.6 1436841H1 686 906 SEQ ID Template Component Start Stop NO: ID ID

14 245251,6 g 1301526 726 979 14 245251.6 83990448 1283 1417 14 245251.6 5902523H1 694 996 14 245251,6 2154086H1 740 1016 14 245251.6 917108H1 686 847 14 245251.6 2767517H1 686 922 14 245251.6 83862612 1283 1419 14 245251,6 83848684 6 142 14 245251.6 1814125H1 1258 1419 14 ~ 245251,6 3682120H1 697 991 14 245251.6 2053508H1 751 1005 14 245251,6 3291620H1 686 907 14 245251.6 83862415 1283 1419 14 245251.6 545078H1 734 994 14 245251.6 3280782H1 759 1005 14 245251.6 5376980H1 475 673 14 245251.6 3749492H1 686 950 14 245251.6 83847665 10 142 14 245251.6 1469717H1 864 1150 14 245251.6 2442618H1 869 1184 14 245251.6 516105076 873 1570 14 245251.6 281458376 874 1553 14 245251.6 5216384H1 888 1183 14 245251.6 g 1313327 885 1234 14 245251.6 506895H1 887 1161 14 245251.6 2246148H1 888 1183 14 245251.6 82032570 892 1215 14 245251.6 82033061 892 1312 14 245251.6 6105423H1 892 1228 14 245251.6 1212338H1 894 1249 14 245251.6 2681270H1 894 1239 14 245251.6 2408072H1 894 1201 14 245251.6 774022H1 894 1152 14 245251.6 4667376H1 894 1218 14 245251.6 2629364H1 894 1225 14 245251.6 2260118H1 894 1198 14 245251.6 4372704H1 895 1264 14 245251.6 464993H1 896 1176 14 245251.6 3027714H1 896 1274 14 245251.6 1856953H1 911 1241 14 245251.6 2410246H1 911 1181 14 245251,6 4750638H2 911 1243 14 245251.6 1294624H1 913 1179 14 245251,6 738970H1 921 1241 14 245251.6 g 1775058 924 1381 14 245251,6 81618108 929 1261 14 245251.6 82336997 938 1260 14 245251,6 1979648H1 940 1271 14 245251.6 1990936H1 941 1143 14 245251.6 966663H1 946 1300 104 .

SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 4371102H1 955 1331 14 245251.6 81315094 957 1239 14 245251.6 4369280H1 963 1293 14 245251.6 1905865H1 993 1281 14 245251.6 81972974 997 1364 14 245251.6 4068060H1 1006 1188 14 245251.6 83597449 1007 1595 14 245251.6 1657456H1 1009 1264 14 245251.6 4996367H1 1014 1326 14 245251.6 81758102 1094 1593 14 245251.6 81623171 1100 1594 14 245251.6 82824662 1099 1590 14 245251.6 82526734 1101 1590 14 245251.6 84108545 1103 1592 14 245251.6 82328692 1105 1593 14 245251.6 814904H1 1104 1425 14 245251.6 2870889H1 1108 1460 14 245251.6 5295918H1 686 922 14 245251.6 83890756 1283 1419 14 245251.6 3086975H1 686 955 14 245251.6 83990539 1283 1416 14 245251.6 83847105 1283 1417 14 245251.6 83989389 6 142 14 245251.6 1333963H1 686 884 14 245251.6 84077443 9 142 14 245251.6 3180014H1 686 913 14 245251.6 83849458 8 142 14 245251.6 4619650H1 686 907 14 245251.6 83989412 1283 1416 14 245251.6 491316H1 686 911 14 245251.6 84077428 7 142 14 245251.6 1647829H1 686 881 14 245251.6 83848848 1283 1416 14 245251.6 705929H1 686 889 14 245251.6 83806474 1283 1418 14 245251.6 2540850H1 686 937 14 245251.6 2301130H1 715 965 14 245251.6 83849235 1283 1411 14 245251.6 127489H1 686 893 14 245251.6 83848866 1283 1419 14 245251.6 1876624H1 383 664 14 245251.6 84085932 9 142 14 245251.6 84077334 1283 1419 14 245251.6 83890303 1283 1415 14 245251.6 3384767H1 725 969 14 245251.6 3688995H1 686 945 14 245251.6 1215027H1 839 975 14 245251.6 83847032 1283 1416 14 245251.6 83807516 8 142 14 245251.6 5102970H1 686 941 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 1802892H1 736 973 14 245251.6 g3842338 7 142 14 245251.6 3286343H2 719 969 14 245251.6 1874116H1 374 653 14 245251.6 g3806912 1283 1416 14 245251.6 g3847485 6 142 14 245251.6 619293H1 687 930 14 245251.6 1258505H1 720 968 14 245251.6 g3989388 1283 1411 14 245251.6 6007911H1 686 974 14 245251.6 2149173H1 686 956 14 245251.6 g3848208 1283 1419 14 245251.6 2992493H1 686 946 14 245251.6 650586H1 379 638 14 245251,6 g3849247 1283 1416 14 245251.6 5910613H1 686 972 14 245251,6 g4077711 1283 1419 14 245251.6 4510726H1 704 973 14 245251,6 g3848062 1283 1417 14 245251,6 6106933H1 686 919 14 245251,6 5115225H1 697 970 14 245251,6 g3846901 6 142 14 245251,6 2513695H2 686 907 14 245251,6 g4326234 1283 1419 14 245251.6 3158887H1 686 935 14 245251.6 2706363H1 756 1102 14 245251.6 g4535116 756 1070 14 245251,6 3883004H1 760 1087 14 245251.6 5301496H1 760 1055 14 245251.6 4096707H1 760 1122 14 245251.6 2863619H1 763 1162 14 245251.6 2867319H1 763 1102 14 245251.6 g1281850 767 1331 14 245251.6 g1576704 773 1232 14 245251.6 g1298432 777 1130 14 245251.6 3837476H1 784 1091 14 245251.6 3010150H1 785 1128 14 245251.6 3010801H1 785 1123 14 245251.6 g2204501 790 1201 14 245251.6 g2217814 791 1325 14 245251.6 g1060431 795 1137 14 245251.6 3918458H1 803 1125 14 245251.6 5697844H1 803 1122 14 245251.6 g2591145 815 1249 14 245251,6 4573806H1 818 1102 14 245251.6 4914643H1 820 1142 14 245251.6 908962H1 833 1192 14 245251.6 2132022T6 833 1548 14 245251.6 4628839H1 832 1120 14 245251.6 3550659H1 835 1213 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 g674861 839 1124 14 245251.6 706061H1 843 1165 14 245251,6 2061068H1 851 1161 14 245251.6 5264515F6 853 1331 14 245251.6 g2539208 854 1344 14 245251,6 2408850H1 856 1132 14 245251,6 6006938H1 863 1213 14 245251.6 6007037H1 863 1228 14 245251.6 3171466H1 866 1199 14 245251.6 g1124148 1283 1592 14 245251.6 g3803160 1285 1600 14 245251.6 g2942025 1286 1598 14 245251.6 3160175H1 1288 1592 14 245251.6 g1740568 1300 1593 14 245251.6 2300048H1 1302 1557 14 245251.6 82877399 1307 1594 14 245251.6 82728321 1309 1591 14 245251.6 1491834H1 1310 1593 14 245251.6 2862613H1 1317 1592 14 245251.6 945012H1 1322 1598 14 245251.6 88471 b8 1313 1593 14 245251.6 84327571 1325 1590 14 245251.6 1507186H1 1330 1569 14 245251,6 3970589H1 1334 1595 14 245251.6 209179H1 1334 1535 14 245251.6 207014H1 1334 1582 14 245251.6 3967178H1 1335 1590 14 245251.6 83058131 1337 1592 14 245251.6 3967462H1 1335 1591 14 245251.6 82787682 1337 1594 14 245251.6 83154417 1337 1594 14 245251.6 2361006H1 1338 1590 14 245251.6 2362930H1 1339 1590 14 245251.6 83001273 1339 1590 14 245251.6 83960768 1341 1592 14 245251.6 942262H1 1345 1592 14 245251.6 902954H1 1349 1593 14 245251.6 4506855H1 1353 1590 14 245251.6 81265337 1360 1599 14 245251.6 1419110H1 1365 1590 14 245251.6 81264701 1373 1599 14 245251.6 81227017 1374 1600 14 245251.6 83884934 1385 1589 14 245251.6 83884396 1388 1590 14 245251.6 83884926 1390 1587 14 245251.6 83846626 1390 1593 14 245251,6 83849105 1390 1541 14 245251.6 83884831 1391 1593 14 245251,6 83842214 1391 1590 14 245251.6 83846730 1393 1590 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 83846909 1393 1586 14 245251.6 82657904 1087 1590 14 245251.6 84525345 1090 1592 14 245251.6 83239030 1088 1599 14 245251.6 870032H1 1092 1407 14 245251.6 5597455H1 1093 1365 14 245251.6 1898558H1 697 967 14 245251.6 84071850 1283 1419 14 245251.6 2452174H1 686 897 14 245251.6 2842830H1 380 650 14 245251.6 3686824H1 686 972 14 245251.6 84077526 9 142 14 245251.6 3782176H1 686 945 14 245251.6 1535425H1 861 972 14 245251.6 83848055 1283 1419 14 245251.6 3119950H1 699 977 14 245251.6 3884464H1 686 806 14 245251.6 83842568 6 142 14 245251.6 3507042H1 695 977 14 245251.6 2512439H1 686 909 14 245251.6 84085946 1283 1416 14 245251.6 4405615H1 686 943 14 245251.6 5896519H1 694 977 14 245251.6 83845926 1283 1419 14 245251.6 3330695H1 686 929 14 245251.6 83847726 1283 1416 14 245251.6 3157747H1 693 975 14 245251.6 1622382H1 686 909 14 245251.6 83862513 1283 1419 14 245251,6 1656661H1 686 873 14 245251.6 83845948 8 142 14 245251.6 3028871H1 686 967 14 245251.6 3809687H1 686 977 14 245251.6 83990041 1283 1417 14 245251,6 2451959H1 573 669 14 245251.6 4551365H 699 976 1 .

14 245251.6 83847599 6 142 14 245251.6 5172386H1 721 980 14 245251.6 83845822 1283 1416 14 245251.6 4824541H1 726 980 14 245251.6 83931555 1283 1418 14 245251.6 84006049 9 142 14 245251.6 2481849H1 686 907 14 245251.6 6026544H1 686 978 14 245251.6 83862408 1283 1416 14 245251.6 5893562H1 694 984 14 245251.6 3141501H1 686 935 14 245251.6 82899544 48 137 14 245251.6 83842538 9 142 14 245251.6 1897745H1 686 935 SE6~ Template Component Start Stop ID NO: ID ID

14 245251.6 g3807515 10 142 14 245251.6 3698231H1 686 964 14 245251.6 1680096H1 454 670 14 245251.6 3575006H1 686 976 14 245251.6 3945268H1 696 980 14 245251.6 g3990060 1283 1418 14 245251.6 1630619H1 740 961 14 245251.6 6026541H1 686 983 14 245251.6 282261H1 821 987 14 245251.6 83989332 1283 1416 14 245251.6 82714757 6 127 14 245251.6 83848017 1283 1418 14 245251.6 4909050H1 691 864 14 245251.6 84077616 1283 1419 14 245251.6 5016694H1 709 985 14 245251.6 82715675 1342 1421 14 245251.6 83890469 1283 1415 14 245251.6 82020485 727 976 14 245251.6 81548162 1304 1422 14 245251.6 84086845 1283 1419 14 245251.6 3095012H1 686 984 14 245251.6 83990363 1283 1416 14 245251.6 4012002H1 686 964 14 245251.6 82198225 1301 1421 14 245251.6 83989049 10 142 14 245251.6 2960954H1 686 985 14 245251.6 84189209 1283 1419 14 245251.6 4268413H1 686 983 14 245251.6 850512H1 756 961 14 245251.6 4238523H1 696 976 14 245251.6 83989140 1283 1419 14 245251.6 8715951 690 981 14 245251.6 83736535 1367 1423 14 245251.6 2512088H1 686 984 14 245251.6 84284258 9 142 14 245251.6 4379339H1 686 936 14 245251.6 83890461 1283 1419 14 245251.6 3182012H1 687 981 14 245251.6 4706886H1 686 932 14 245251.6 83846611 1283 1415 14 245251.6 2322530H1 736 987 14 245251.6 83990086 7 142 14 245251.6 3839096H1 686 938 14 245251.6 321302H1 765 984 14 245251.6 83989015 1283 1416 14 245251.6 1990623H1 686 928 14 245251.6 3683615H1 696 987 14 245251.6 84086491 1283 1416 14 245251.6 1619567H1 686 866 14 245251.6 3078410H1 686 986 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 84080312 9 142 14 245251.6 2908167H1 686 987 14 245251.6 3671767H1 686 892 14 245251.6 82037878 686 961 14 245251.6 84077435 1283 1416 14 245251.6 1603854H1 686 878 14 245251.6 81199063 686 987 14 245251.6 84017782 1283 1419 14 245251.6 1347327H1 686 907 14 245251.6 8927989 359 637 14 245251.6 3324035H1 697 990 14 245251.6 84086445 7 142 14 245251,6 2546965H2 686 862 14 245251.6 4343132H1 873 997 14 245251.6 84077453 1283 1419 14 245251.6 4334622H1 686 944 14 245251.6 8847231 356 637 14 245251.6 83846130 1283 1416 14 245251.6 84018630 1283 1416 14 245251.6 2101272H1 4 114 14 245251,6 2587234H1 686 903 14 245251.6 3574372H1 686 979 14 245251,6 83694286 1050 1590 14 245251,6 81315095 1061 1599 14 245251.6 210059H1 1053 1331 14 245251.6 83279541 1055 1598 14 245251.6 83736864 1055 1595 14 245251,6 4974349H1 1056 1417 14 245251.6 83665039 1061 1592 14 245251.6 3888183H1 1063 1401 14 245251.6 1530540H1 1063 1345 14 245251.6 81274050 1076 1590 14 245251.6 002239H1 1065 1548 14 245251.6 1297924H1 1065 1381 14 245251.6 3479370H1 1065 1328 14 245251.6 1312352H1 1068 1333 14 245251.6 506800H1 1068 1356 14 245251.6 81364437 1077 1592 14 245251.6 82214112 1072 1591 14 245251.6 1267456H1 1074 1366 14 245251.6 82820951 1079 1594 14 245251.6 1311167H1 1082 1398 14 245251.6 82401841 1080 1593 14 245251.6 83735785 1082 1596 14 245251.6 82217605 1083 1595 14 245251.6 g 1576739 1085 1592 14 245251.6 8674787 1092 1587 14 245251.6 4010641H1 697 1030 14 245251.6 2506513H1 697 956 14 245251.6 795092H1 697 957 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 5221852H2 697 979 14 245251.6 5687479H1 697 979 14 245251.6 1483887H1 697 973 14 245251.6 1449209H1 697 917 14 245251.6 3747027H1 697 1031 14 245251.6 1594015H1 697 942 14 245251.6 1455584H1 697 966 14 245251.6 1593886H1 697 922 14 245251.6 3379095H1 699 975 14 245251.6 526768H1 699 978 14 245251.6 g1970187 700 1120 14 245251.6 5913596H1 699 1013 14 245251.6 g1997336 702 1120 14 245251.6 g864282 704 1088 14 245251.6 4307655H1 702 1087 14 245251.6 3766134H1 702 1031 14 245251.6 4545031H1 705 1032 14 245251.6 g 1501684 705 1219 14 245251.6 g 1321292 707 1229 14 245251.6 2496344H1 705 1103 14 245251.6 4675111H1 705 964 14 245251.6 3482217H1 705 1067 14 245251.6 4070047H1 705 1031 14 245251.6 2997014H1 706 1031 14 245251.6 g1623223 711 1097 14 245251.6 5164521H1 709 999 14 245251.6 4196137H1 686 806 14 245251.6 358653H1 701 923 14 245251.6 1370775H1 686 823 14 245251.6 3759039H1 686 907 14 245251.6 600085H1 422 656 14 245251.6 1575013H1 686 897 14 245251.6 1000003H1 686 925 14 245251.6 2049730H1 686 925 14 245251.6 5282003H1 686 919 14 245251.6 5161050H1 557 657 14 245251.6 2134833H1 696 928 14 245251,6 4667193H1 689 928 14 245251,6 1593935H1 686 898 14 245251.6 1786467H1 686 919 14 245251,6 1299188H1 686 917 14 245251.6 2616796H1 686 913 14 245251,6 5699823H1 686 928 14 245251.6 4833390H1 691 907 14 245251.6 2450956H1 686 913 14 245251,6 1416169H1 686 927 14 245251.6 4902593H1 686 853 14 245251.6 685823H1 686 795 14 245251.6 1378622H1 686 892 14 245251.6 2203295H1 686 912 SEQ ID Template Component Start Stop NO: ID ID

14 245251,6 4873526H1 686 906 14 245251.6 1567661H1 686 889 14 245251.6 4265241H1 554 660 14 245251.6 4565002H1 686 930 14 245251.6 5028562H1 686 931 14 245251.6 3315321H2 686 916 14 245251.6 179704H1 686 857 14 245251.6 5043044H1 691 923 14 245251.6 3272310H1 686 923 14 245251.6 5590795H1 686 871 14 245251.6 4374880H1 686 930 14 245251.6 2942376H1 722 932 14 245251.6 2669414H1 686 932 14 245251.6 2051081H1 686 932 14 245251.6 778957H1 686 836 14 245251.6 3383437H1 686 924 14 245251.6 2502860H1 702 939 14 245251.6 g1548213 686 828 14 245251.6 1558658H1 686 895 14 245251.6 2742568H1 693 934 14 245251.6 5844527H1 686 928 14 245251.6 3237925H1 413 660 14 245251.6 1654956H1 686 903 14 245251.6 1212747H1 686 906 14 245251.6 2110510H1 695 937 14 245251,6 2670483H1 697 937 14 245251.6 3887565H1 686 937 14 245251.6 2278236H1 692 939 14 245251.6 1549915H1 686 880 14 245251.6 1915263H1 686 926 14 245251.6 3174435H1 686 912 14 245251,6 931246H1 686 925 14 245251.6 1524019H1 724 944 14 245251,6 2630203H1 686 914 14 245251.6 6063419H1 686 867 14 245251.6 1557962H1 686 876 14 245251,6 1519653H1 686 820 14 245251,6 g1970343 686 927 14 245251,6 1643982H1 686 870 14 245251.6 2636948H1 686 944 14 245251.6 3236095H1 686 910 14 ~ 245251.63290990H1 695 944 14 245251.6 2916653H1 439 664 14 245251.6 2347442H1 686 901 14 245251.6 2160657H1 705 942 14 245251.6 1612904H1 686 861 14 245251.6 1602311H1 686 865 14 245251.6 2479177H1 686 940 14 245251.6 3276325H1 686 942 14 245251,6 3342181H1 686 942 SE6~ Template Component Start Stop ID NO: ID ID

14 245251.6 3414248H1 700 942 14 245251.6 4244690H1 424 664 14 245251.6 1657385H1 686 887 14 245251.6 2060168H1 686 942 14 245251.6 2724864H1 686 940 14 245251.6 2507348H1 718 943 14 245251.6 3439967H1 686 916 14 245251.6 3875717H1 712 946 14 245251.6 3930892H1 686 944 14 245251.6 2876429H1 686 930 14 245251.6 1663347H1 686 897 14 245251.6 745654H1 715 946 14 245251.6 5714032H1 402 bbl 14 245251.6 6013561H1 686 939 14 245251.6 3368428H1 687 945 14 245251.6 4673619H1 686 945 14 245251.6 4356555H1 686 921 14 245251.6 2984258H1 691 943 14 245251.6 6073987H1 686 945 14 245251.6 2435338H1 686 881 14 245251.6 3416993H1 698 943 14 245251.6 4108736H1 686 944 14 245251.6 1793902H1 686 938 14 245251.6 3429779H1 686 943 14 245251.6 1522075H1 468 664 14 245251.6 3282589H1 701 946 14 245251.6 5781877H1 686 925 14 245251.6 1311376H1 686 946 14 245251.6 2478308H1 686 912 14 245251.6 476523H1 1305 1419 14 245251.6 3406437H1 . 6 108 14 245251.6 4998161H1 686 936 14 245251.6 1759883H1 686 943 14 245251.6 2426656H1 686 918 14 245251.6 2357554H1 686 898 14 245251.6 911731H1 686 947 14 245251.6 3361812H1 686 947 14 245251.6 4349129H1 686 875 14 245251.6 4847891H1 686 922 14 245251.6 929615H1 686 943 14 245251.6 4593502H1 686 938 14 245251.6 g1956732 701 948 14 245251.6 3325687H2 554 664 14 245251.6 1504636H1 699 951 14 245251.6 3357413H1 686 931 14 245251.6 2093969H1 7 120 14 245251.6 3888045H1 686 917 14 245251.6 4400406H1 704 949 14 245251.6 4675188H1 686 895 14 245251.6 1833267H1 696 949 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 3531646H1 1290 1419 14 245251.6 4675103H1 686 823 14 245251.6 612029H1 686 948 14 245251.6 83861897 1283 1417 14 245251.6 83861915 10 142 14 245251.6 4585634H1 ' 686 807 14 245251.6 81187227 736 954 14 245251.6 83806416 6 142 14 245251.6 8809795 688 920 14 245251.6 83806236 1283 1417 14 245251.6 5184838H1 686 929 14 245251.6 83806383 9 142 14 245251.6 83862381 6 142 14 245251.6 5102972H1 686 938 14 245251.6 83806305 1283 1416 14 245251.6 4049171H1 686 952 14 245251.6 5399585H1 686 806 14 245251.6 83806377 8 142 14 245251.6 1609289H1 686 ' 861 14 245251.6 81985106 688 952 14 245251.6 1631116H1 740 958 14 245251.6 83846850 1283 1419 14 245251.6 3371627H1 686 934 14 245251.6 83842256 1283 1415 14 245251.6 81948393 686 952 14 245251.6 83849535 8 142 14 245251.6 1353725H1 686 906 14 245251.6 3811303H1 395 637 14 245251.6 83849274 1283 1417 14 245251.6 770658H1 692 958 14 245251.6 1709346H1 686 889 14 245251.6 83923055 1283 1416 14 245251.6 1351272H1 686 917 14 245251.6 2497443H1 686 952 14 245251.6 6007158H1 686 958 14 245251.6 84086359 1283 1419 14 245251.6 83849526 1283 1419 14 245251.6 5905094H1 686 959 14 245251.6 83847515 1283 1417 14 245251.6 3040561H1 686 954 14 245251.6 1886946H1 686 956 14 245251.6 4764852H1 686 958 14 245251.6 83847084 1283 1417 14 245251.6 83845943 1283 1419 14 245251.6 5685528H1 686 956 14 245251.6 83846660 9 142 14 245251.6 83845949 1283 1419 14 245251.6 3400315H1 688 927 14 245251.6 81953701 688 939 14 245251.6 5833060H1 686 954 SE6~ Template Component Start Stop ID NO: ID ID

14 245251.6 83989265 1283 1417 14 245251.6 4049178H1 686 954 14 245251.6 82038078 686 957 14 245251.6 212969H1 686 851 14 245251,6 84074607 9 142 14 245251.6 83990111 1283 1419 14 245251.6 4265942H1 688 945 14 245251.6 83990156 1283 1415 14 245251,6 1859765H1 446 666 14 245251.6 83847576 9 142 14 245251.6 81320366 594 1041 14 245251.6 2039935H1 596 882 14 245251.6 5299657H1 601 870 14 245251.6 4947763H1 623 800 14 245251.6 799795H1 640 890 14 245251.6 81957419 644 1200 14 245251.6 1503008H1 669 974 14 245251.6 1503133H1 669 1024 14 245251,6 1703102H1 670 907 14 245251.6 5945265H1 671 9b5 14 245251.6 4154972H1 672 973 14 245251.6 4783070H1 677 947 14 245251.6 2729061H1 680 956 14 245251.6 4817713H1 683 981 14 245251.6 2604603H1 685 958 14 245251,6 2300089H1 685 963 14 245251,6 3647926H1 689 1020 14 245251.6 5120725H1 690 1026 14 245251,6 083810H1 692 952 14 245251,6 4409416H1 694 881 14 245251,6 4057228H1 694 996 14 245251.6 5395048H1 696 1005 14 245251.6 3481334H1 693 1055 14 245251.6 4218418H1 694 988 14 245251.6 4820226H1 695 855 14 245251.6 4073954H1 694 1017 14 245251.6 1315458H1 695 975 14 245251.6 3600571H1 696 1025 14 245251.6 3776260H1 696 1029 14 245251.6 3588749H1 695 1055 14 245251,6 2814583F6 696 1360 14 245251.6 1229362H1 696 948 14 245251.6 5732270H1 695 982 14 245251.6 g 1727842 696 1088 14 245251.6 3660326H1 696 915 14 245251.6 4198443H1 697 808 14 245251.6 1455236H1 695 976 14 245251.6 2343111H1 696 992 14 245251.6 3513953H1 696 992 14 245251.6 4999458H1 696 993 SEQ ID Template Component Start Stop NO: ID ID

14 245251.6 2261362H1 696 975 14 245251.6 3029907H1 696 1017 14 245251.6 5121569H1 696 1011 14 245251.6 4537506H1 695 979 14 245251.6 3321759H1 696 1013 14 245251.6 2307802H1 697 981 14 245251.6 2307804H1 697 979 14 245251.6 3012456H1 697 951 14 245251.6 2504610H1 697 952 14 245251.6 3362687H1 697 990 14 245251.6 3748602H1 696 901 14 245251.6 3316419H1 697 990 14 245251,6 2814582H1 696 992 14 245251.6 2272892H1 697 993 14 245251.6 1807854H1 696 976 14 245251.6 g2466185 697 1219 14 245251.6 2132022H1 697 996 14 245251.6 213202286 697 1408 14 245251.6 3073883H1 697 997 14 245251.6 2125224H1 697 1003 14 245251.6 2269903H1 697 816 14 245251.6 1459722H1 697 922 14 245251.6 4562893H1 697 981 14 245251.6 1496792H1 696 922 14 245251.6 5221884H2 697 975 ~

14 245251.6 5572366H1 697 928 14 245251,6 2771241H1 697 967 14 245251.6 1573610H1 697 974 14 245251.6 1867126H1 697 1002 14 245251.6 1507375H1 697 928 14 245251,6 1573473H1 697 932 14 245251.6 3267774H1 697 1002 14 245251,6 3163705H1 697 973 14 245251,6 3272193H1 696 970 14 245251,6 2985313H1 697 1009 14 245251.6 3495519H1 697 1014 14 245251.6 3943155H1 697 981 14 245251.6 3812545H1 697 1032 14 245251.6 2708787H1 697 1024 14 24 ~51.b 3639075H 697 1030 14 245251.6 81940776 733 1099 14 245251.6 8908409 734 1122 14 245251.6 5865030H1 736 1078 14 245251.6 4050960H1 736 1049 14 245251.6 3819250H1 751 1088 14 245251.6 g 1761139 757 1219 14 245251.6 g 1967349 756 1382 14 245251.6 81618353 729 1108 14 245251.6 g 1364436 729 1251 14 245251.6 81727492 715 1095 SEQ ID Template Component Start Stop NO: ID ID

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15 252875.1 2420169H1 2950 3197 15 252875.1 2227025H1 2953 3202 15 252875.1 1948888H1 2953 3118 15 252875.1 96767181 2957 3598 15 252875.1 2682662H1 2956 3270 15 252875.1 967671H1 2957 3272 15 252875.1 g1303166 2964 3269 15 252875.1 4323462H1 2975 3231 15 252875.1 3774157H1 2982 3300 15 252875.1 2384295H2 2984 3216 15 252875.1 4156648H1 2992 3290 15 252875.1 5373633H1 2994 3209 15 252875.1 190297H1 3005 3261 15 252875.1 19029781 3005 3659 15 252875.1 3222225H1 3006 3362 15 252875.1 2197579H1 3012 3284 15 252875.1 4334641H1 3016 3321 15 252875.1 1739115H1 3031 3225 15 252875.1 2076112H1 3031 3345 15 252875.1 4588978H1 3031 3144 15 252875.1 1929325H1 3033 3287 15 252875.1 1698356H1 3044 3278 15 252875.1 774049H1 3044 3278 15 252875.1 3201988H1 3045 3229 15 252875.1 g 1165436 3045 3537 15 252875,1 4079815H1 3046 3338 15 252875.1 546658H1 3054 3386 15 252875,1 3243004H1 3061 3315 15 252875.1 2285730H1 3074 3327 15 252875.1 4957381H1 3075 3353 15 252875,1 g1165609 3101 3371 15 252875.1 548503H1 3112 3289 15 252875,1 434752H1 3117 3345 15 252875.1 1665374H1 3115 3374 15 252875,1 3766307H1 3116 3255 15 252875.1 5301677H1 3118 3294 15 252875.1 619409H1 3124 3411 15 252875.1 2134475H1 3129 3401 15 252875.1 1328119H1 3134 3432 15 252875.1 g835219 3135 3529 15 252875.1 3414825H1 3663 3915 15 252875.1 g4285757 3666 3843 15 252875.1 3992325H1 3673 3977 15 252875.1 1684593H1 3674 3906 15 252875.1 g1690764 3683 3831 15 252875.1 507054H1 3693 3932 15 252875.1 g 1493946 3705 3840 15 252875.1 2113227H1 3709 4000 15 252875.1 g4457753 3711 3844 15 252875.1 1601661H1 3712 3926 SEQ ID Template Component Start Stop NO: ID ID

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15 252875.1 2313534H1 3569 3818 15 252875.1 1258470F1 3572 4196 15 252875.1 84304393 3571 3842 15 252875.1 2692250H1 3572 3831 15 252875.1 1258470H1 3572 3836 15 252875.1 81275416 3572 4230 15 252875.1 3809069H1 3582 3895 15 252875.1 81152594 3583 3840 15 252875.1 82321801 3588 3838 15 252875.1 8835206 3590 3840 15 252875.1 2808212H1 3607 3935 15 252875.1 1916784H1 3616 3905 15 252875.1 1251826H1 3619 3778 15 252875.1 1251826F1 3619 3830 15 252875.1 83920452 2265 2604 15 252875.1 2457404H1 2267 2520 15 252875.1 5216436H1 2268 2523 15 252875.1 8572819 2271 2614 15 252875.1 2685979H1 2291 2546 15 252875.1 4311421H1 2289 2413 15 252875.1 1387882H1 2291 2569 15 252875.1 1994174H1 2291 2402 15 252875.1 1386461H1 2291 2425 15 252875.1 3296980H1 2293 2560 15 252875.1 3742330H1 2307 2605 15 252875.1 2839295H1 2309 2585 15 252875.1 2615762H1 2321 2606 15 252875.1 2115669H1 2327 2594 15 252875.1 3248377H1 2331 2428 15 252875.1 1892380H1 2352 2493 15 252875.1 82217857 2382 2726 15 252875.1 3425510H1 2390 2665 15 252875.1 3666290H1 2391 2590 15 252875.1 3133325H1 2392 2667 15 252875.1 g 1897668 2395 2756 15 252875.1 034289H1 2400 2657 15 252875.1 g 1062015 2406 2733 15 252875.1 3542538H1 2407 2673 15 252875.1 3542586H1 2407 2668 15 252875.1 2969209H1 2424 2686 15 252875.1 4358014H1 2434 2716 15 252875.1 3657619H1 2435 2724 15 252875.1 82930924 2236 2642 15 252875.1 031953H1 2440 2723 15 252875.1 030691H1 2440 2652 15 252875.1 81154198 2441 2728 15 252875.1 2069257Th 2441 2867 15 252875.1 2744591H1 2441 2699 15 252875.1 81062277 2451 2739 15 252875.1 1945843H1 2476 2722 SE9 ID Template Component Start Stop NO: ID ID

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SEQUENCE LISTING
<110> INCYTE GENOMICS, INC.
Hodgson, David M.
Lincoln, Stephen E.
Russo, Frank D.
Spiro, Peter A.
Banville, Steve C.
Bratcher, Shawn R.
Dufour, Gerard E.
Cohen, Howard J.
Rosen, Bruce Chalup, Michael S.
Hillman, Jennifer L.
Jones, Anissa L.
Yu, Jimmy Y.
Greenawalt, Lila B.
Panzer, Scott R.
Roseberry, Ann M.
Wright, Rachel J.
Daniels, Susan E.
<120> SECRETORY MOLECULES
<130> PT-1064 PCT
<140> To Be Assigned <141> Herewith <150> 60/147,501; 60/147,500 <151> 1999-08-05; 1999-08-05 <160> 26 <170> PERL Program <210> 1 <211> 1973 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 001978.1 <400> 1 gcaggttcgg ggtcggccgg cctgcgcgtg ggcttgcgag gacgctgttc gtcccctgcg 60 ctggggtgtc cgacagcgag gaggagaacg acgcacggag cccgcgcgac tggaaccagc 120 aaagctccat ctgtcggcag aggagaaggg ggaggaggca cggccgaggc aaacgagcgg 180 acgcctcgtc gccgggtgcc ggtatcaccc cgctgcaacg ccttccagca aaagccaccg 240 cggcccgggt tgcagcagcc ggacggatgc caaggccaca cggcagccac gggggcagcc 300 gtcgcagtcg ccgtcccaca cgggctgcgg acaccaaggg ttgctaatga agtgattgag 360 aagaaacagt gaacatcctc atttcacaga taagacaaca tggatcagcc ttttactgtg 420 aattctctga aaaagttagc tgctatgcct gaccatacag atgtttccct aagcccagaa 480 gagcgagtcc gtgccctaag caagcttggt tgtaatatca ccatcagtga agacatcact 540 ccacgacgtt actttaggtc tggagtagag atggagaggt ggcgctgtgt atttggaaga 600 aggaaatttg gaaaatgcct ttgttcttta taataaattt ataaccttat ttgtagaaaa 660 gcttcctaac catcgagatt accagcaatg tgcagtacct gaaaagcagg atattatgaa 720 gaaactgaag gagattgcat tcccaaggac agatgaattg aaaaacgacc ttttaaagaa 780 atataacgta gaataccaag aatatttgca aagcaaaaac aaatataaag ctgaaattct 840 caaaaaattg gagcatcaga gattgataga ggcagaaagg aagcggattg ctcagatgcg 900 ccagcagcag ctagaatcgg agcagtttct gtttttcgaa gatcaactca agaagcaaga 960 gttagcccga ggtcaaatgc gaagtcagca aacctcaggg ctgtcagagc agattgatgg 1020 gagcgctttg tcctgctttt ccacacacca gaacaattcc ttgctgaatg tatttgcaga 1080 tcaacctaat aaaagtgatg caaccaatta tgctagccac tctcctcctg taaacagggc 1140 cttaacgcca gctgctactc taagtgctgt tcagaattta gtggttgaag gactgcgatg 1200 tgtagttttg ccagaagatc tttgccacaa atttctgcaa ctggcagaat ctaatacagt 1260 gagaggaata gaaacctgtg gaatactctg tggaaaactg acacataatg aatttactat 1320 tacccatgta attgtgccaa agcagtctgc gggaccagac tattgtgaca tggagaatgt 1380 agaggaatta ttcaatgttc aggatcaaca tgatctcctc actctaggat ggatccatac 1440 acatcccact caaactgcat ttttatccag cgttgatctt cacactcact gttcctatca 1500 actcatgttg ccagaggcca ttgccattgt ttgctcacca aagcataaag acactggcat 1560 cttcaggctc accaatgctg gcatgcttga ggtttctgct tgtaaaaaaa agggctttca 1620 tccacacacc aaggagccca ggctgttcag tatatgcaaa catgtgttgg taaaagacat 1680 aaaaataatt gtgttggatc tgaggtgata tgttctgaat gtaagcaccg tcaacatcag 1740 acacctactc atggacatgt ggttgccgga ttttcttaag atgtttccag aaatgactga 1800 tattttatat ttatacattt tagatgacaa agcttgatat ttattgctgt tgcacatttt 1860 aaagttttct ttttgggttg ctctgtgtca agagaggtta catggtgtta aatcggtacc 1920 tgataatgta cccaaatact atggccagat aataaattgt gctgcaaaca aca 1973 <210> 2 <211> 3199 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 002588.4 <400> 2 gtcccttccc ctcacccgct ccacgccctc ctgggccgag tggagttggg tggtgtcggg 60 agcctctccc tgaggggcac cgcgtcttca ggagctgggc ctccagtgcg gcgcgatgtc 120 aggcgcggtg acagctctgt gagtccgagg ccgcggccgt ggcgctgggc ggctgcgggg 180 cctgaccggt ccgctcatgg tgccgccacg acgccatcgc ggggcaggaa ggccaggggt 240 gctgagttct tcacctcctt ttagactgag atctgccaag ttttccggca ttgctcttga 300 ggatctcaga agggctctta agacaagact gcaaatggtg tgtgtatttg tcatgaaccg 360 aatgaattcc cagaacagtg gtttcactca gcgcaggcga atggctcttg ggattgttat 420 tcttctgctt gttgatgtga tatgggttgc ttcctctgaa cttacttcgt atgtttttac 480 ccagtacaac aaaccattct tcagcacctt tgcaaaaaca tctatgtttg ttttgtacct 540 tttgggcttt attatttgga agccatggag acaacagtgt acaagaggac ttcgcggaaa 600 gcatgctgct ttttttgcag atgctgaagg ttactttgct gcttgcacaa cagatacaac 660 tatgaatagt tctttgagtg aacctctgta tgtgcctgtg aaattccatg atcttccaag 720 tgaaaaacct gagagcacaa acattgatac tgaaaaaacc cccaaaaagt ctcgtgtgag 780 gttcagtaat atcatggaga ttcgacagct tccgtcaagt catgcattgg aagcaaagtt 840 gtctcgcatg tcatatcctg tgaaagaaca agaatccata ctgaaaactg tggggaaact 900 tactgcaact caagtagcga aaattagctt ttttttttgc tttgtgtggt ttttggcaaa 960 tttgtcatat caagaagcac tttcagacac acaagttgct atagttaata ttttatcttc 1020 aacttccgga ctttttacct taatccttgc tgcagtattt ccaagtaaca gtggagatag 1080 atttaccctt tctaaaacta ttagctgtaa ttttaagcat tggaggcgtt gtactggtaa 1140 acctgggcag ggtctgaaaa acctgctgga agagacacag taggttccat ttggtctctt 1200 gctggagcca tgctctatgc tgtctatatt gttatgatta agagaaaagt agatagagaa 1260 gacaagttgg atattccaat gttctttggt tttgtaggtt tgtttaatct gctgctctta 1320 tggccaggtt tctttttact tcattatact ggatttgagg acttcgagtt tcccaataaa 1380 gtagtattaa tgtgcattat cattaatggc cttattggaa cagtactctc agagttcctg 1440 tggttgtggg gctgctttct tacctcatca ttgataggca cacttgcact aagccttaca 1500 atacctctgt ccataatagc tgacatgtgt atgcaaaagg tgcagttttc ttggttattt 1560 tttgcaggag ctatccctgt atttttttca ttttttattg taactctcct atgccattat 1620 aataattggg atcctgtgat ggtgggaatc agaagaatat ttgcttttat atgcagaaaa 1680 Catcgaattc agagagttcc agaagacagc gaacagtgtg agagtctcat ttctatgcac 1740 agtgtttctc aggaggatgg agctagttag ctgtctgttg tctgtagccc agcttgataa 1800 tggaactata cagcgaagag acaatctctg gcaagttttt gtagaaaaaa tgtttcagtg 1860 cctagtctga aaaataacag tttgagttct ttgaaactct aaaatatatt tttctcatac 1920 ctgttttctt cattttcata atgaagcact ttgctatgta gctgtgtaca tatcactaca 1980 gttataggaa gtttcagtct acagtccatc caaaggacca acctgcctta cacatctcaa 2040 ggaattcagc tgttgaaatc atttgaacta atcaaggaat aaatcctaat gttctgggac 2100 tttattttca catgttaaat gctggaatat attatgaaaa tgttttcaag aaatcactta 2160 agtgttcata gaccagtatt tctgacaggt aaaatgctaa aataagctac ctgtaataag 2220 tgtggattat atttttgggt tttgtagaat attgcaaatt aaccacacaa aaaatgttta 2280 atttatgcaa caagcatgtt tgtgcaaatt tcatgggact ttaaaaagaa taagtatttg 2340 agaaaatatc tggttcactt acactacatt tactgtatta ttcttttata gcattaggtg 2400 ccttgtattt taaatctgtg acaaaccatg gcaaattttt aaaggggaag tattattata 2460 aaatgaagaa atatgtattt ctaaaggcta tattgctgta aacttaattg ataaagctct 252D
gtttaattta gagttttgaa gaaatagtct cccttcaatt aagaaatttt cataatggaa 2580 tgatttaaat tgaagtgaca aagagtatta ttaaaataca atgtttatac gtgtatttgt 2640 gtattgtaga tgtatcaagt gatttctaat ttttttcaca tatgaatgtg ccagattact 2700 ctagaactag atgtctcttc tttaaataat tttagttttc ctgaataaat ttgtaatggt 2760 taaagtacca agtaagtaag gcgagaaggg attctgtttt taaaatcaca tcagaacttt 2820 tcctctacta agattataaa ttaaatgtaa aatactccta attgcaattc ttaaacttag 2880 gccttacatg tacttattat gcaactgctc ctggactcta ttcaccatag atatcagtaa 2940 acgtatgtcc caggattcac aggcttttga ttaatcaata ttcttttcaa gtttgctgtg 3000 aagagtttag ttctcttcaa aatttcttaa ctaatctgat ttttaggaat tctctttgca 3060 gtgtttagct tcctattcac attcttaaaa ttgctttggt gttaccatga gtctaaaatg 3120 aagtttagcc ttccttttgt ttcattctga gaacttctat attatattac ctttaaaaat 3180 tgtttatgat attaaattt 3199 <210> 3 <211> 2235 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 201759.3 <400> 3 gcggcgacgg cggccgttgc tgcgccgggt actggggtcg ctgcctgagg cgcaggcgcc 60 gtggactcca cccgccccgg ggcctgggct cgctgtggac tcgtcatggc gaccgagcag 120 aggcctttcc acctggtggt gttcggcgcg tctggcttca ccggccagtt cgtgaccgag 180 gaggtggccc gggagcaggt ggacccggag cggagtcccg cctgccctgg gccgtggcgg 240 gccgctcccg ggagaagctg cagcgggtgc tggagaaggc ggccctgaag ctgggaagac 300 caacactgta catctgaagt tggaatcatc atctgtgata ttgctaatcc agcctcgctt 360 gatgaaatgg ctaaacaggc aacagttgtc ctcaattgcg taggaccata tcggttttat 420 ggagaacctg taataaaagc atgtattgaa aatggagcca gttgtatcga catcagtgga 480 gaacctcagt ttctggaact aatgcaactg aagtatcatg agaaagctgc agacaaaggg 540 gtttatatca ttggaagcag cggctttgac tccattccag cagatctggg agtaatatat 600 accagaaata aaatgaatgg tactttgact gctgtggaaa gtttcctgac tatacattca 660 ggacctgagg ggttgagcat tcatgatggt acctggaagt cagcaattta tggttttgga 720 gatcagagta atttgagaaa actaagaaat gtatcaaatc tgaaacctgt cccgctcatt 780 ggtccaaaat tgaagagaag gtggccaatt tcttattgtc gggaactcaa aggttattcc 840 attcctttta tgggatctga tgtgtctgtt gtaaggagga ctcaacgtta cttgtatgaa 900 aatttagagg aatcaccagt tcagtatgct gcgtatgtaa ctgtgggagg catcacctct 960 gttattaagc tgatgtttgc aggacttttc tttttgttct ttgtgaggtt tggaattgga 1020 aggcaacttc ctcataaaat tcccatggtt cttctccttt gggctatttt tcaaaacaag 1080 gcccaacaca aaaacagatt gatgctgcct cattcacgct gacattcttt ggtcaaggat 1140 acagccaagg cactggtaca gataagaaca aaccaaatat caaaatttgt actcaggtga 1200 aaggaccaga ggctggctat gtggctaccc ccatagctat ggttcaggca gccatgactc 1260 ttctaagtga tgcttctcat ctgcctaagg cgggcggggt cttcacacct ggagcagctt 1320 tttccaaaac aaagttgatt gacagactca acaaacacgg tattgagttt agtgttatta 1380 gcagctctga agtctaaaca ctggaagaat taactgaagt cataacgtgc gtgaattaac 1440 agcttctcta tttgatattt gaaattcttc tgtaagcctg tctgagtgta tgtggaaacg 1500 attgtcaaat ctaaaatatc tatatattaa aaagtaggaa attgtcctag cttaccctaa 1560 atttcaaatc tgagttgatt ttgtgatttt attgcttata acagagaact catatttgac 1620 atattttttt cattgatgtg ttcctggtag attttcacga atgagctggc aggtctaatg 1680 ggggaggcgg cgtcccagtc tgtgttgcag cagcattctc atcgggggtg cgcacaccat 1740 cgttactgtc gggcagtaac tgccgcttgc cttgccgcag taggagggaa atctcacctt 1800 ccttccacat actgtcttga gcctttgcta aattaaactg cactttttgc tatttttgcc 1860 tagtttttcg ccaatctaca ctgattttgg actgttacct aagttgaaaa ataaaaggtt 1920 gtcaatcgaa tggtggttta atgtttggac ctgccgatgt atttgtatag tggtagaaac 1980 atgctgctta agtggcctaa cctgtttctt gccaataagt aggcttatca ttttatcttt 2040 acgtaattct atatctgtga ctaggttttt aaggatacag cttataagtt gctatcaatt 2100 ttcactacct aagcagaatt tttctctaat ttactttttg tattttaact aggttttaca 2160 tggaagccct aaaataaggc aaaagacttt ttcttttgta ataagcatat aataaacacg 2220 tatatacata gcaaa 2235 <210> 4 <211> 1953 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 208184.1 <400> 4 gcggccgctg tagttgcggc ggtccagtcg tagcccggcc gcccgcgcct gtccggtccg 60 gtccggccac ggaggcagcg cagcggcggg actccgagcc taccccgccg agtgagctgc 120 gccgcaccgt gccgtcccac ccggcaccca ccagtccgat ggggccgcag cggcggctgt 180 cccctgccgg ggccgcccta ctctggggct tcctgctcca gctgacagcc gctcaggaag 240 caatcttgca tgcgtctgga aatggcacaa ccaaggacta ctgcatgctt tataaccctt 300 attggacagc tcttccaagt accctagaaa atgcaacttc cattagtttg atgaatctga 360 cttccacacc actatgcaac ctttctgata ttcctcctgt tggcataaag agcaaagcag 420 ttgtggttcc atggggaagc tgccattttc ttgaaaaagc cagaattgca cagaaaggag 480 gtgctgaagc aatgttagtt gtcaataaca gtgtcctatt tcctccctca ggtaacagat 540 ctgaatttcc tgatgtgaaa atactgattg catttataag ctacaaagac tttagagata 600 tgaaccagac tctaggagat aacattactg tgaaaatgta ttctccatcg tggcctaact 660 ttgattatac tatggtggtt atttttgtaa ttgcggtgtt cactgtggca ttaggtggat 720 actggagtgg actagttgaa ttggaaaact tgaaagcagt gacaactgaa gatagagaaa 780 tgaggaaaaa gaaggaagaa tatttaactt ttagtcctct tacagttgta atatttgtgg 840 tcatctgctg tgttatgatg gtcttacttt atttcttcta caaatggttg gtttatgtta 900 tgatagcaat tttctgcata gcatcagcaa tgagtctgta caactgtctt gctgcactaa 960 ttcataagat accatatgga caatgcacga ttgcatgtcg tggcaaaaac atggaagtga 1020 gacttatttt tctctctgga ctgtgcatag cagtagctgt tgtttgggct gtgtttcgaa 1080 atgaagacag gtgggcttgg attttacagg atatcttggg gattgctttc tgtctgaatt 1140 taattaaaac actgaagttg cccaacttca agtcatgtgt gatacttcta ggccttctcc 1200 tcctctatga tgtatttttt gttttcataa caccattcat cacaaagaat ggtgagagta 1260 tcatggttga actcgcagct ggaccttttg gaaataatga aaagttgcca gtagtcatca 1320 gagtaccaaa actgatctat ttctcagtaa tgagtgtgtg cctcatgcct gtttcaatat 1380 tgggttttgg agacattatt gtaccaggcc tgttgattgc atactgtaga agatttgatg 1440 ttcagactgg ttcttcttac atatactatg tttcgtctac agttgcctat gctattggca 1500 tgatacttac atttgttgtt ctggtgctga tgaaaaaggg gcaacctgct ctcctctatt 1560 tagtaccttg cacacttatt actgcctcag ttgttgcctg gagacgtaag gaaatgaaaa 1620 agttctggaa aggtaacagc tatcagatga tggaccattt ggattgtgca acaaatgaag 1680 aaaaccctgt gatatctggt gaacagattg tccagcaata atattatgtg gaactgctat 1740 aatgtgtcat tgattttcta caaatagact tcgacttttt aaattgactt ttgaattgac 1800 aatctgaaag agtcttcaat gatatgcttg caaaaatata tttttatgag ctggtactga 1860 cagttacatc ataaataact aaaacgcttt gcttttaatg ttaaagttgt gccttcacat 1920 taaataaaac atatggtctg tgtagtttcc gag ' 1953 <210> 5 <211> 1867 <212> DNA
<213> Homo sapiens <220>

<221> misc_feature <223> Incyte ID No: 212029.3 <220>
<221> unsure <222> 54, 89, 1164, 1166-1187 <223> a, t, c, g, or other <400> 5 ctaccctgct cctcagcctg tgagaacaga tgtggccgtc ctgcggtacc agcnaccccc 60 tgagtatggg gtaacgagcc gcccatgcna acttccgttc ccatcaacca tgcagcagca 120 cagccccatg tcctcccaga cctcttccgc cagcgggcca ctgcactctg tctccctgcc 180 gcttccactc ccgatggccc tgggtgctcc acagcccccg cctgccgcct cccccagcca 240 gcagcttggt ccagatgcct ttgcgattgt ggagcgagcc cagcaaatgg tggagatatt 300 aacagaggag aaccgggtgc ttcaccagga acttcagggt tactacgaca atgccgacaa 360 gctccacaag tttgaaaaag aacttcagag aatttcggaa gcctatgaaa gtctggtcaa 420 gtctaccacc aagcgagaat cgctggacaa ggccatgaga aacaaattgg aaggcgagat 480 tagaagactt catgatttca acagagacct ccgagatcga ctagagactg ctaacaggca 540 actatccagc agggaatacg aagggcatga agacaaagct gcagaggggc attatgcttc 600 ccagaacaaa gaattcttga aggaaaagga gaaattagaa atggagttag cagcagtgcg 660 gactgcaagt gaggaccatc ggagacacat cgagatcctg gaccaggctt tgagcaacgc 720 ccaggccagg gtcatcaagc tggaagagga gttacgagag aagcaagcat atgttgagaa 780 agttgagaag ctgcagcagg ccctgaccca gctgcagtct gcatgtgaga agcgagaaca 840 gatggagcgg agactgcgga cttggctgga gagagagctg gatgcactga gaacccagca 900 gaaacatgga aatggccagc cagccaacat gccggaatac aatgccccag ccctcctgga 960 acttgtgcgg gagaaggagg agcggatcct ggccctggag gccgacatga caaagtggga 1020 gcagaagtac ctggaggaga gcaccatccg acactttgcc atgaatgccg cagccactgc 1080 agcagctgag agggacacca cgatcatcaa ccactcacgg aatggcagct acggagagag 1140 ctcgctggag gcccacatct ggcnannnnn nnnnnnnnnn nnnnnnncca acagaaggtg 1200 tcaggacatg gaatacacta ttaaaaatct ccatgccaaa atcatagaga aagatgctat 1260 gattaaggtc ctgcagcagc gatctcgtaa agatgccggg aagacagact cctccagcct 1320 acgtcctgcc cgctccgttc catccatagc agcagctact gggacacact ctcgccagac 1380 ctctcttacc agcagccagc tggctgagga aaagaaggaa gagaagacct ggaaggggag 1440 cataggattg ctgctgggga aggagcacca tgagcatgcc tctgccccac tgctgctacc 1500 cccacccacc tcagcactgt cctccatagc ctccactacg gcagccagca gtgcccacgc 1560 caagacaggc agcaaggaca gcagcacaca gactgacaag agtgccgagc tcttctggcc 1620 cagcatggcc tcccttccca gccgcggccg gctgagcacg acccctgctc acagccccgt 1680 cctgaaacac ccagcggcca aagggaccgc agagaaactg ggtatgtggg ctaccccacc 1740 ttgatgcccc tgaaaactgt ggaactgtct ggcctaagag aatcttttgt tgagctagag 1800 aggaagcagg ggcacccatc agctcttact ctatggggat gctattctaa tgcacttagg 1860 atatgtg 1867 <210> 6 <211> 1325 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 213446.2 <400> 6 cgggggctga tggaagtgca gtgggggctg gagagggcac cctagtgagt tggcttttct 60 ctccttcggt gcctttggtt gggctcgagg cccggggtcg gaggccatca ggacaagagt 120 gtgggacttg gaagggcagc cacctggagc ttggaagggg ctgtatccag catgctccaa 180 ggccacagct ctgtgttcca ggccttgctg gggaccttct tcacctgggg gatgacagca 240 gctggggcag ctctcgtgtt cgtattctct agtggacaga ggcggatctt agatggaagt 300 cttggctttg ctgcaggggt catgttggca gcttcctatt ggtctcttct ggccccagca 360 gttgagatgg ccacgtcctc tgggggcttc ggtgcctttg ccttcttccc tgtggctgtt 420 ggcttcaccc ttggagcggc ttttgtctac ttggctgacc tcctgatgcc tcacttgggt 480 gcagcagaag acccccagac ggccctggca ctgaacttcg gctctacgtt gatgaagaag 540 aagtctgatc ctgagggtcc cgcgctgctc ttccctgaga gtgaactttc catccggata 600 gacaagagtg agaatggtga ggcatatcag agaaagaagg cggcagccac tggccttcca 660 gagggtcctg ctgtccctgt gccttctcga gggaatctgg cacagcccgg cggcagcagc 720 tggaggagga tcgcactgct catcttggcc atcactatac acaacgttcc agagggtctc 780 gctgttggag ttggatttgg ggctatagaa aagacggcat ctgctacctt tgagagtgcc 840 aggaatttgg ccattggaat cgggatccag aatttccccg agggcctggc tgtcagcctt 900 cccttgcgag gggcaggctt ctccacctgg agagctttct ggtatgggca gctgagcggc 960 atggtggagc ccctggccgg ggtctttggt gcctttgccg tggtgctggc tgagcccatc 1020 ctgccctacg ctctggcctt tgctgccggt gccatggtct acgtggtcat ggacgacatc 1080 atccccgaag cccagatcag tggtaatggg aaactggcat cctgggcctc catcctggga 1140 tttgtagtga tgatgtcact ggacgttggc ctgggctagg gctgagacgc ttcggacccc 1200 gggaaaggcc atacgaagaa acagcagtgg ttggcttcta tgggacaaca agcttctttc 1260 ttcacattaa aacttttttc cttcctctct tcttcatctc attatcctga ttgactctaa 1320 ttata 1325 <210> 7 <211> 1808 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 228864.4 <400> 7 ggcgtggcct ccggccggct cctctgctgt tgccaaggga aactgccgcg aggaggcgga 60 aggagcagag gaccggcagc cggcgtcgag gcggggcgcg ggaacgacgg cggccatggc 120 ggcctcgggg cccgggtgtc gcagctggtg cttgtgtccc gaggtgccat ccgccacctt 180 cttcactgcg ctgctctcgc tgctggtttc cgggcctcgc ctgttcctgc tgcagcagcc 240 ccctggcgcc ctacgggcct cacgctgaag tccgaggccc ttcgcaactg gcaagtttac 300 aggctggtaa cctacatctt tgtctacgag aatcccatct ccctggctct gcggcgctat 360 catcatctgg cgctttgctg gcaatttcga gagaaccgtg ggcaccgtcc gccactgctt 420 cttcaccgtg atcttcgcca tcttctccgc tatcatcttc ctgtcattcg aggctgtgtc 480 atcactgtca aagctggggg aagtggagga tgccagaggt ttcaccccag tgggcctttg 540 ccatgctggg agtcaccacc gtccgttctc ggatgaggcg ggccctggtg tttggcatgg 600 ttgtgccctc agtcctggtt ccgtggctcc tgctgggtgc ctcgtggctc attccccaga 660 cctctttcct cagtaatgtc tgcgggctgt ccatcgggct ggcctatggc ctcacctact 720 gctattccat cgacctctca gagcgagtgg cgctgaagct cgatcagacc ttccccttca 780 gcctgatgag gaggatatcc gtgttcaagt acgtctcagg gtcttcagcc gagaggaggg 840 cagcccagag ccggaaactg aacccggtgc ctggctccta ccccacacag agctgccacc 900 ctcacctgtc cccaagccac cctgtgtccc agacgcagca cgccagtggt tcagaagctg 960 gcctcctggc cctccctggc acccccgggc acatgcccac cttgcctccg taccagcctg 1020 cctccggcct gtgctatgtg caagaaccac tttggtccaa accccacctc ctccagtgtc 1080 tacccagctt ctgcgggcac ctccctgggc atccagcccc ccacgcctgt gaacagccct 1140 ggcacggtgt attctggggc cttgggcaca ccaggggctg caggctccaa ggagtcctcc 1200 agggtcccca tgccctgaga gaatttctag ggaagtcatc tcacttggcc ttctgaaggt 1260 cctccctaag agtctcctga caaaagttac ttattgaaca cctctatgtg ccaggctctg 1320 tgttgggtac tttgatcaat gcccctgttt cagtctcatc tgtactcacg gcagccctgt 1380 ggagtacggt gtactggccc agcttacaga tgcagaaagc gagacgttct gccatcagat 1440 aaagtcacgt ggctctttag taacacggac aaggctcctc gccaaggaac tcgtggcaga 1500 agagggcagc agttggcagt agctgccgat gtctgtcccc agctccacca ttcctccctg 1560 tggctgtgcc atgctcgtgg tttcagtgtc cgtgtgtcca tgtgtctgcc cttcaggagc 1620 tcgcagctgg tgtgcttggc ggtcccaggc ctgtgtagtg tctctcccct gctgcgggcg 1680 cccccacccc gattcctctc cccagaagcg gtgggatggg cccccatgaa ctgcagcagc 1740 atgctgaggt gtccatgttg tctgcctttg tataaagaaa cagcctctga aaaaaaaaaa 1800 aaaaaaat 1808 <210> 8 <211> 2992 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 229840.3 <400> 8 aacacgagtc caagctgcag ctgggcaggg attgcggggt gccggccgtc tgagtttttt 60 taaaactgct tcgccgcgaa gtctgtctgc agccaaaatg tccaacagaa acaacaacaa 120 gcttcccagc aacctgccgc agttacagaa tctaatcaag cgagacccgc cggcctacat 180 cgaggagttt ctacagcagt ataatcacta caaatccaat gtggagattt tcaaattgca 240 accaaataaa cccagcaaag aactagcaga gctggtgatg tttatggcac agattagtca 300 ctgctaccca gagtacctaa gtaattttcc tcaagaggtg aaagatcttc tctcctgcaa 360 tcataccgta ttggatccag atctgcgaat gacattttgc aaagctttga tcttgctgag 420 aaataagaat ctcatcaatc catcaagcct gctagaactc ttctttgaac tttttcgttg 480 ccatgataaa cttctgcgaa agactttata cacacatatt gtgactgata tcaagaatat 540 aaatgcaaaa cacaagaaca ataaagtgaa tgtagtattg caaaatttca tgtacaccat 600 gttaagagat agcaatgcaa ccgcagccaa gatgtcttta gatgtaatga ttgaactcta 660 cagaaggaac atctggaatg atgcaaaaac tgtcaatgtt atcacaactg catgtttctc 720 taaggtcacc aagatattag ttgccgcttt gacattcttt cttgggaaag atgaagatga 780 aaaacaggac agtgactccg aatctgagga tgatggacca acagcaagag acctgctagt 840 acaatatgct acagggaaga aaagttccaa aaacaagaaa aagttggaaa aggcaatgaa 900 agtgctcaag aaacaaaaaa agaagaaaaa accagaggtg tttaactttt cagccattca 960 cttgattcat gatccccaag attttgcgga aaaactacta aagcagcttg agtgctgtaa 1020 ggagaggttt gaagtgaaga tgatgctcat gaaccttatc tccagattgg tgggaattca 1080 tgagcttttc ctcttcaatt tctatccctt tttgcaaagg tttctgcagc cccaccaaag 1140 agaagtaacc aagatccttc tgtttgctgc acaagcatct catcacctag tacccccaga 1200 gattattcaa tcattgctta tgactgtggc aaacaatttt gttaccgaca agaactctgg 1260 agaagtcatg acagtaggaa tcaatgctat aaaggagata acagctcgat gtcctctggc 1320 catgactgaa gaacttctcc aagacctggc tcagtataaa acacacaagg ataagaatgt 1380 aatgatgtct gctagaactt tgattcacct cttccgaaca ctgaatcctc agatgctgca 1440 gaagaaattc cggggtaagc ctacagaggc ctccatagaa gcaagagtac aagaatatgg 1500 agaattagat gctaaagatt acattccagg agcagaagtt ctggaagttg agaaagaaga 1560 gaatgctgaa aatgatgaag atggatggga aagtaccagt ctcagtgagg aggaggatgc 1620 tgatggtgaa tggattgatg tgcaacactc ttccgatgaa gaacagcaag aaatctccaa 1680 gaagctgaac agcatgccca tggaggagcg gaaggccaaa gctgcagcca tcagcactag 1740 ccgagtttta actcaggaag acttccagaa aatccgcatg gcccaaatga gaaaagaact 1800 tgatgctgcc cccgggaaat gccagaagag gaaatacatt gaaatagaca gtgatgaaga 1860 gcccaggggt gaattacttt ctcttcggga cattgaacgc cttcataaaa agccaaagtc 1920 tgacaaagag acaagactag caactgcaat ggctggaaag acagaccgaa aagaatttgt 1980 gaggaagaaa accaaaacaa atccattttc cagttcgaca aataaagaga agaaaaaaca 2040 gaagaacttt atgatgatgc ggtatagcca gaatgtccgg tcaaaaaata agcgttcctt 2100 ccgagaaaaa cagttggcac tacgagatgc acttttgaaa aagagaaaaa gaatgaagta 2160 acttcctggc aagttttcca ttcctagaag aatgctaagt ttgtgtcctt gctctgaaaa 2220 ttggtaaatc aagcatgttt gtttacatta aaaagtccag acacactgta ttgtgaaaac 2280 tgctgaacat gtggcagcaa ttttgtgttt ttattttgga gacggctaat ggtaggaatg 2340 ttaatgtaaa tagtggtggt aatgtaaaat catttcattt atcattcatg caaaaaaaag 2400 tatgtattga gtgcctattc attgtcactg tagatgcaaa acgaatgagc tgtaacccct 2460 tcactcaagg cattgacagc ttagctgtga gggtggacac acatatgtgt atttacagtg 2520 cagtgtaaat agttctgtag tagaggttaa ctccatattt ctgtgaggtc actgaggcct 2580 tatggactaa ctctgtgagg ataggagtta tatattctta taagacaaaa caaaacagga 2640 caatgttaca agagtaagag gttcttactt gtacataggc tttcctgctg aaaacaggcc 2700 cctgctgtac agattttggg tacataattt agctctttta gtcaatccaa gagatttaag 2760 tgaccccccc cccgtgtttt ttttgttttt gtttttgttt tgaatgccat gtaaaggctt 2820 tttggttaag acctcacttt taaaactgcc ttaagtataa atagtacctt tggaatatat 2880 ttagttcatc atttgagctg ccttcatact ggtttcctca gccttccttc agcctgtaat 2940 attttcagcc cactgtttac cttgtctcaa taaaaggttt ctaatgccaa at 2992 <210> 9 <211> 2513 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 231793.2 <400> 9 cccggaacta acctcggctc ccttgggaag gccgcgttgc atggccagga gcagcagtct 60 gggccgcgag tgcgggacac cgaggtcagg tctcggaaag ggaggacctc ctcgtcccca 120 ggggccccag gccaggtgca cccttggccg caggtgcacg gtctccggaa agtgcaggcg 180 cccacgtccc agctggacca tggcgcctcc gcggaacgtg gtgaagattg ccatccagat 240 gcgtgacgcc atcccgcagc tcatccagct ggaccaggcg aagccctggc cgctgtgctg 300 aaggaggtgt gcgacgcgtg gagcctgacg cactctgagc gttacgccct gcagtttgcg 360 gatgggcacc ggagatacat caccgagaat aaccgcgcgg agatcaagaa tggcagcatc 420 ctgtgcctca gcacggcccc agaccttgag gctgagcagc tcttgggtgg gctgcagagt 480 aacagtcctg aagggcgccg ggaagccctg aggcgccttg ttccgctggc ctcggacatg 540 atctttgcca gggaggtcat cagccgtaat gggctccaga tactaggcac catcattgaa 600 gatggggacg acctaggaga ggtgctggcc ctcagcctga gggccttctc agagctcatg 660 gagcacggcg tggtgtcctg ggagactctg agcatcccct ttgtgaggaa ggtggtgtgc 720 tacgtgaaca tgaacctcat ggatgcctcc gtgcctcccc tggcccttgg gctgctggag 780 agtgtgacct tgagcagccc agccctgggc cagctggtca agagcgaggt gcccctggat 840 aggctgctgg tgcacctaca ggtgatgaac cagcagctgc aaaccaaggc catggccctg 900 ctgacagcct tgctgcaggg ggccagccct gtggaacgca agcacatgct tgactatctt 960 tggcagagga accttcgcca gttcatctat aagaacatca tccacagtgc agcaccaatg 1020 ggcgacgaga tggctcatca cctgtacgta ctgcaggctc tcatgctggg gctgctggag 1080 ccgcgcatgc gaacgcccct ggacccctac agccaggagc agcgggagca gctgcaggtc 1140 ctacgccagg ctgccttcga ggtggagggg gagtcctcgg gtgccgggct aagtgctgac 1200 cgtcgccgtt ccctctgtgc ccgagagttc cgcaaactgg gcttttctaa cagcaaccca 1260 gcacaggacc tggagcgcgt gccccccggt ctgctggccc tggacaacat gttgtacttc 1320 tccagaaacg cgcccagcgc gtaacagccg gtttgtgttg gagaacagca gccgcgagga 1380 caagcacgag tgcccctttg cccggggcag catccagctg acggtgctgc tgtgtgagct 1440 gctccgtgtt ggggagccct gctctgagac agcccaggac ttctcaccca tgttcttcgg 1500 ccaagaccag agcttccacg agctcttctg tgtgggcatc cagctgttga ataagacctg 1560 gaaggagatg cgggctacac atggaggact tcgacaaggt catgcaggtg gtgcgggagc 1620 agctggcccg cactctggcc ctgaagccca cttccctgga gctcttccga accaaggtga 1680 atgcgctcac ttatggggag gtgctgcggc tgcggcagac tgaacggctg caccaggagg 1740 gcacactggc tccccctata ctggagctgc gggagaagct gaagccagag ctcatgggcc 1800 tgatccgcca gcagcgcttg ctccgcctct gtgaggggac gctcttccgc aagatcagca 1860 gccggcggcg ccaggataag ctgtggttct gctgcctgtc ccccaaccac aagctgctgc 1920 agtacggaga catggaggag ggcgccagcc cgcctaccct ggagagtctg cccgagcaac 1980 tccctgtggc cgacatgagg gcactcctga caggcaagga ctgcccccat gtccgggaga 2040 agggctccgg gaagcagaac aaggacctct atgagttggc cttctcaatc agctatgacc 2100 gtggggagga ggaagcgtac ctcaacttca ttgccccctc caagcgggag ttctacctgt 2160 ggacagatgg gctcagtgcc ttgctgggca gtcccatggg cagcgagcag acacggctgg 2220 acctggagca gctgctgacc atggagacca agctgcgtct gctggagctg gagaacgtgc 2280 ccatccccga gcggccaccc cctgtgcccc caccccccac caacttcaac ttctgctatg 2340 actgcagcat cgctgaacct tgacagtgtg gctggccatg ggccacagct gcggccactg 2400 cagcagccat gaagggcagt gggtagagga gtgcaggcac cctgaccagc agagattgct 2460 gcagaaataa agtctgcttg gctcttggga tatgttgagc cagctctgta aaa 2513 <210> 10 <211> 1976 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 234137.5 <220>
<221> unsure <222> 1035, 1039, 1051 <223> a, t, c, g, or other <400> 10 gggagtggta gtgggggctg cagctgccgg acccaggtgc ggaagtgcga gggcccaggt 60 ggctgaaggg gccgttagga acatccaagc ggtggggcac aggcagatcc ccgacctgac 120 ctggaccacc cttctcctct tggcccgccc cttcaactcg cctccgctta ggtctggatt 180 ggccccgccc cctgacctga gcctggtcct tcttcaggca ctgacccttg acctccggtg 240 gctcccccat ctctcaggcg cgatggctac gggcgcggat gtacgggaca ttctagaact 300 cgggggtcca gaaggggatg cagcctctgg gaccatcagc aagaaggaca ttatcaaccc 360 ggacaagaaa aaatccaaga agtcctctga gacactgact ttcaagaggc ccgagggcat 420 gcaccgggaa gtctatgcct tgctctactc tgacaagaag gatgcacccc cactgctacc 480 cagtgacact ggccagggat accgtacagt gaaggccaag ttgggctcca agaaggtgcg 540 gccttggaag tggatgccat tcaccaaccc ggcccgcaag gacggagcaa tgttcttcca 600 ctggcgacgt gcagcggagg agggcaagga ctaccccttt gccaggttca ataagactgt 660 gcaggtgcct gtgtactcgg agcaggagta ccagctttat ctccacgatg atgcttggac 720 taaggcagaa actgaccacc tctttgacct cagccgccge tttgacctgc gttttgttgt 780 tatccatgac cggtatgacc accagcagtt caagaagcgt tctgtggaag acctgaagga 840 gcggtactac cacatctgtg ctaagcttgc caacgtgcgg gctgtgccag gcacagacct 900 taagatacca gtatttgatg ctgggcacga acgacggcgg aaggaacagc ttgagcgtct 960 ctacaaccgg accccagagc aggtggcaga ggaggagtac ctggctacag gagctgcgca 1020 agattgatgc ccggnagang gagcgggaga nacgcagcca ggacctgcag aagctgatca 1080 cagcggcaga caccactgca gagcagcggc gcacggaacg caaggccccc aaaaagaagc 1140 taccccagaa aaaggaggct gagaagccgg ctgttcctga gactgcaggc atcaagtttc 1200 cagacttcaa gtctgcaggt gtcacgctgc ggagccaacg gatgaagctg ccaagctctg 1260 tgggacagaa gaagatcaag gccctggaac agatgctgct ggagcttggt gtggagctga 1320 gcccgacacc tacggaggag ctggtgcaca tgttcaatga gctgcgaacg acctggtgct 1380 gctctacgag ctcaagcagg cctgtgccaa ctgcgagtat gagctgcaga tgctgcggca 1440 ccgtcatgag gcactggccc gggctggtgt gctagggggc cctgccacac cagcatcagg 1500 cccaggcccg gcctctgctg agccggcagt gactgaaccc ggacttggtc ctgaccccaa 1560 ggacaccatc attgatgtgg tgggcgcacc cctcacgccc aattcggtaa gagtctggac 1620 aggctgggag gcacgcctgg gccctgcgag tgagcacatg cacatgggtg taggggctcc 1680 tctccctcta gtgcctgcag caggaacgat catcacttct gtgcgagtct gagactgagg 1740 gtaggagtgg gttgaccagt gggcgtcctt gtccctgagc gtgtgaagca catgcactaa 1800 gcctgactca ggccttgggg ggtcactgac ctcaatgcct tctgtgtatc ctcagagaaa 1860 gcgacgggag tcggcctcca gctcatcttc cgtgaagaaa gccaagaagc cgtgagaggc 1920 cccacggggt gtgggcgacg ctgttatgta aatagagctg ctgagttgga aaaaaa 1976 <210> 11 <211> 1400 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 234671.14 <220>
<221> unsure <222> 1397 <223> a, t, c, g, or other <40D> 11 ggcagttctc gtccagagcc caggtaatcc gggcgggatc agctagcgtc gcgatgtgat 60 gacgtcaggc cccggccagg ccgggagtgg cgtgctgggc cgtgcgcggc tgcggtacgg 120 cgtgttggtc ccagcggttc agctgaggta gggacgtgct gtaggccgga atgttaccgg 180 ctgttggatc tgtggatgag gaagaggatc ctgcggagga ggattgtcct gaattggttc 240 ccattgagac gacgcaaagc gaggaggagg aaaagtctgg cctcggcgcc aagatcccag 300 tcacaattat caccgggtat ttaggtgctg ggaagacaac acttctgaac tatattttga 360 cagagcaaca tagtaaaaga gtagcggtca ttttaaatga atctggggaa ggaagtgcgc 420 tggagaaatc cttagctgtc agccaaggtg gagagctcta tgaagagtgg ctggaactta 480 gaaacggttg cctctgctgt tcagtgaagt gaggaatgtg tttactgtgt acatggttta 540 ctagaaatgt ttattgatta tatttccagc tttaattttc ttgagtaatt taactgaatt 600 tacacagttt gcttcattgt attttcaaac aaatagaaaa taaacttatt aggaagcatt 660 ttcttaaagt gtttcttgct gtcttttcta tctgctctaa tgttttggtc cttttattga 720 gtttttattg cttttgatgt cagggcttat ttaatctcta gtgcatgaaa gtctcatatg 780 taaaaaatga ttattctgaa tttaatctgt cattggtcat atttctaagt gttcaacctt 840 ataaaaaaaa taaatgacta tcaaaaaaag aaaaacctta cattatgttc tactagttaa 900 gttttcaagg acagtgttca ctagtctacc atagacccta gaagagttac ccaacacata 960 gtagcactca aatatttgtt gaatgaatta taaaaatgac tacttgtatt gttaattttg 1020 tgtattctag tgaattaaat ctcttcggca tcatttactc ccttaggtat ttgactttgt 1080 gtcaaatgtt ttggcaagga taaaattata acagactttc ttgaacaacc aaaatataat 1140 ctattaagga ttttccttca cttttgataa aataagaaaa aaggaaatta aaaccttgca 1200 tcctaatgta aaatagaatt atatggtgtt taatatcagt gtccctttag ctattatatt 1260 aaactactat agttaataaa ttttatcatt attttgtatg ttggttttta aaaatttcat 1320 aaagctataa aaagatactt ggtcagataa agtttcctct gcttttaatt ttaataaagt 1380 attattatgt atatganaaa 1400 <210> 12 <211> 2126 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 241236.3 <220>
<221> unsure <222> 1157 <223> a, t, c, g, or other <40D> 12 tgacccccta ttgagagaga ttgctcctgg ccccctcacc acaccctctg tcccagattc 60 agatgtagcc tggtcttttt tggaaagatg ttccatctct cctgccctcc aggctccact 120 cctggtccct gcttcctctg tggttctgcc ccaggcacac tgcactgccc atcctgtcca 180 gaggagatct tctcggctct gcagtactcg ggcactgagg tgcctctgca gtggttgcgc 240 tcagaactgc cctacgtcct ggagatggtg gctgagctgg ctggacagca ggaccctggg 300 ctgggtgcct tttcctgtca ggaggcccgg agagcctggc tggatcgtca tggcaacctt 360 gatgaagctg tggaggagtg tgtgaggacc aggcgaagga aggtgcagga gctccagtct 420 ctaggctttg ggcctgagga ggggtctctc caggcattgt tccagcacgg aggtgatgtg 480 tcacgggccc tgactgagct acagcgccaa cgcctagagc ccttccgcca gcgcctctgg 540 gacagtggcc ctgagcccac cccttcctgg gatgggccag acaagcagag cctggtcagg 600 cggcttttgg cagtctacgc actccccagc tggggccggg cagagctggc actgtcactg 660 ctgcaggaga cacccaggaa ctatgagttg ggggatgtgg tagaagctgt gaggcacagc 720 caggaccggg ccttcctggc gccgcttgct tgcccaggag tgtgccgtgt gtggctgggc 780 cctgccccac aaccggatgc aggccctgac ttcctgtgag tgcaccatct gtcctgactg 840 cttccgccag cacttcacca tcgccttgaa ggagaagcac atcacagaca tggtgtgccc 90D
tgcctgtggc cgccccgacc tcaccgatga cacacagttg ctcagctact tctctaccct 960 tgacatccag cttcgcgaga gcctagagcc agatgcctat gcgttgttcc ataagaagct 1020 gaccgagggt gtgctgatgc gggaccccaa gttcttgtgg tgtgcccagt gctcctttgg 1080 cttcatatat gagcgtgagc agctggaggc aacttgtccc cagtgtcacc agaccttctg 1140 tgtgcgctgc aagcgcnagt gggaggagca gcaccgaggt cggagctgtg aggacttcca 1200 gaactggaaa cgcatgaacg acccagaata ccaggcccag ggcctaggca atgtatcttc 1260 aggaaaacgg cattgactgc cccaaatgca agttctcgta cgccctggcc cgaggaggct 1320 gcatgcactt tcactgtacc cagtgccgcc accagttctg cagcggctgc tacaatgcct 1380 tttacgccaa gaataaatgt ccagagccta actgcagggt gaaaaagtcc ctgcacggcc 1440 accaccctcg agactgcctc ttctacctgc gggactggac tgctctccgg cttcagaagc 1500 tgctacagga caataacgtc atgtttaata cagagcctcc agctggggcc cgggcagtcc 1560 ctggaggcgg ctgccgagtg atagagcaga aggaggttcc caatgggctc agggacgaag 1620 cttgtggcaa ggaaactcca gctggctatg ccggcctgtg ccaggcacac tacaaagagt 1680 atcttgtgag cctcatcaat gcccactcgc tggacccagc caccttgtat gaggtggaag 1740 agctggagac ggccactgag cgctacctgc acgtacgccc ccagcctttg gctggagagg 1800 atccccctgc ttaccaggcc cgcttgttac agaagctgac agaagaggta cccttgggac 1860 agagtatccc ccgcaggcgg aagtagctga gggcaagggt cccgatgagg gtcccatggc 1920 ctgctccctc aggaacagct ccagcaccaa taaagaggca tcttaccacc caggcttctt 1980 ggtggtcctt cttcctggtg ccaccatcta ggggcaccag ggaaagagcg gggtgaacag 2040 agctttgctg aaaagggccc cctgcaacct agtgcctgac cctccctgga ctcaggacca 2100 ggaaggagtt gacaccctgg atggtc 2126 <210> 13 <211> 2674 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 245014.1 <400> 13 gagtattgga agacttgcga tggaagaaat ctaccagaaa ccatttcaga cattaatgtt 60 tttgattcga gattggagct atccttatga acattcatat ggtttggaag gtggaaagca 120 atttcttgaa aagagattac aggtaaaaca aaatcaacat gaagagcttc agaatgtaag 180 gaagcacata cacaattgtt tctcaaatct tggttgcttc cttttgccac atcctggtct 240 taaagttgca actaatccta gttttgatgg gagattgaaa gatattgatg aagactttaa 300 acgagagctt cgaaatctgg ttccattgct gcttgcccct gaaaatttgg tagaaaaaga 360 gataagtgga tctaaagtca cttgtagaga tcttgtagaa tattttaagg cttacatcaa 420 aatctatcaa ggagaagaac ttccacatcc aaagtccatg cttcaggcaa cagctgaagc 480 taataatctt gctgcagtag caggagcaag agatacctat tgtaaaagta tggaacaggt 540 atgtggaggg gacaagcctt acattgcacc ttcagatctg gagcgaaaac acttggatct 600 caaggaagtg gcgataaaac aatttcgttc agtaaaaaag atgggtggag atgagttctg 660 ccgtcgttat caggaccagc ttgaagctga aattgaagaa acctatgcaa attttataaa 720 gcacaatgat ggcaaaaata tcttctatgc tgctcgtacc ccagccacac tgtttgcggt 780 catgtttgct atgtatataa tctcaggact gactggcttc attggcctaa actctatagc 840 tgtcttgtgt aaccttgtca tggggttagc actgatattt ctttgtactt gggcatatgt 900 taaatactct ggggagttca gagaaattgg aacagtgatt gatcagattg ctgaaacact 960 atgggaacag gtgttttcca aactgtttga agttactaga cgtcgaatgg ttcaccgtgc 1020 tctttcatca gcacagcgac agagactgtc atccaacaat aacaagaaga aaaattagac 1080 agtattttta acctttttcc tctatctgaa gtgttcacac ttacacatgt aggacaataa 1140 gcaggaccgt ctgggccggt ctgcataaat gctgtataca taccagattt gatgctgcat 1200 atagggtatg gaattgcaca tccatctcat aggaattgta aatggtttga ataagaggaa 1260 agtaattttt gttgcattat aaaatgtcta gtagcatcat aagttttttt gagagaagca 1320 tctttttatt tcccatattc ctggttattt tcatcattgc tttgaattga atttttatat 1380 ctatttttat atgtaactct ttttttacct catgtttttg tttgttttgc acatttctca 1440 taccacaggt attgaagccc ctgggtgata atttgatgga ggaaaacata aggcagtctg 1500 taacaaactc tatcaaagca ggcctgactg accaggtgtc tcatcatgcc agattaaaga 1560 cagactgaca gttcatctcc tcacggactc cactctcttt ttttttcatg cttgctgtac 1620 aatgagaact caaataaaaa taaaccaaag tttacaatca actgtagaag tagtttagtg 1680 taactggctt cacagatggc tgccacagag tgtgaagatt gtttgttagt tttaagcatt 1740 cttttaatgg gctcctaaga catgcagatg gactgaggag cattggttaa tcatgcacct 1800 ttgtgccatg tttaactctt ttatttcttt ttacttaatc taatgttagt gaatttgtct 1860 tatgtaaaag gatatttcag ggaaatattt tcagaaatct atttagagtc tctttaacac 1920 agtgtcccat tgaaatttta atttttagag aatttatgaa tcactgtttc aagaaccaga 1980 ttggaaagac aatgaagcct ttattgagcc actacattaa aagtatatat tgctttactg 2040 ccttcaatac cagtattaca taaatgcatg tatcagaaac ttcacagaaa ttacatggca 2100 actcttgtag ctaagaaagt aattctgagg tgtacatttg tcttgccttt ttaaatttat 2160 aaacttgccc taaaaggaga tgcatatctg ggaaactgaa ctgtcttttt gcagtttagc 2220 cttcatgtat ataaaatatg ccattaattt tattggggaa gaaattccat ccaaaaatgt 2280 tgcctacagc tatgagttaa gagtgtctgt acagtgtgta gcttttattt tctaaaatca 2340 cagatagggc atgtatatga cttataaata tataaatacg attttgtatt aaaagttttg 2400 tagtttatgg caaaatctgg tcctgtggta ggctaaataa gtactgtccc tgtgaaagga 2460 atgtttgtgg ctcatgtcag tgtgtgaatg catagacaat ttgaagtttt tgatatattt 2520 gtgatattta tcttgagcac tgcaatctca cccccccccc gcccaccaag ggaattcaat 2580 gggaatgttt attgtgactt tgtcctctgt tgcattttaa agttatttcc tgtaatttat 2640 tttcagtaca taattaaaaa tttgttgtat atat 2674 <210> 14 <211> 1427 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 245251.6 <400> 14 tggctgagtc aacacatctt tattaaacac ctgaagttac tgggaggagg ccatgatgct 60 ggacacactg tcaaagtcaa tcttctccac aatgttcttg ggtttaatgc tctcttcttg 120 gctacagatg aagatctgcc ccgactcgtc ggcactccag ccgtatttgc tcatccacac 180 ctttagctgg ctgtactttc ggacagagtc ttcaaagcca gttatacctt ccaagaggtc 240 catgttttca tccagggctt gccagaaggc ctggaaatgg caggtctcca gcaggtcccc 300 gaggtacaaa atctgtcgga ttggccgttc ttcttgatgt gcctggtcga tcatgcactt 360 gcacagggtg aagtctgtgt gcggcaagtt ggtgagggcc ttcagcagga tctgggcggt 420 gaccgtggtc tgaaagaagg ctgggttgaa ctggtacagc ttcaggacag ccaggttggc 480 ttccagatca taggcatttt ccttggcctg cgtctctaca tagcgctcca gggtggccag 540 gttctcagga ttgtaccctt gagcaacttg cccacgttgg ctctcatctg ctcaaacatc 600 gccatgactt ctgtcgcctt ccacaaccag ggctggaggc taacactgac ccggcacggc 660 gtcctcaagg acgggaacag gaagaggtca gtgttagcct ccagccctgg ttgtggaagg 720 cgacagaagt catggcgatg tttgagcaga tgagagccaa cgtgggcaag ttgctcaagg 780 gtatcgacag gtacaatcct gagaacctgg ccaccctgga gcgctatgta gagacgcagg 840 ccaaggaaaa tgcctatgat ctggaagcca acctggctgt cctgaagctg taccagttca 900 acccagcctt ctttcagacc acggtcaccg cccagatcct gctgaaggcc ctcaccaact 960 tgccgcacac agacttcacc ctgtgcaagt gcatgatcga ccaggcacat caagaagaac 1020 ggccaatccg acagattttg tacctcgggg acctgctgga gacctgccat ttccaggcct 1080 tctggcaagc cctggatgaa aacatggacc tcttggaagg tataactggc tttgaagact 1140 ctgtccgaaa gtttatctgc catgttgtgg gtatcactta ccagcacatt gaccgctggc 1200 tgctggccga gatgctcggg gatctgtcgg acagccagct aaaggtgtgg atgagcaaat 1260 acggctggag tgccgacgag tcggggcaga tcttcatctg tagccaagaa gagagcatta 1320 aacccaagaa cattgtggag aagattgact ttgacagtgt gtccagcatc atggcctcct 1380 cccagtaact tcaggtgttt aataaagatg tgttgactca gcccaaa 1427 <210> 15 <211> 4404 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 252875.1 <220>
<221> unsure <222> 9, 20, 26 <223> a, t, c, g, or other <400> 15 ctgtggcgnt ggcgctggtn gctgcngcgg cagccggcgg cacggcgctc gagcggttcc 60 tgtcagggtc agccggcggg ccccctgggt ggtccacctg caaatcgcgg agcggggccc 120 cagggatcga tggcgatgaa ctataacgcg aaggatgaag tggacggtgg gccccCgtgt 180 gctccggggg gcaccgcgaa gactcggaga ccggataaca cggccttcaa acagcaacgg 240 ctgccagctt ggcagcccat ccttacggct ggcacggtgc tacctatttt cttcatcatc 300 ggtctcatct tcattcccat cggcattggc atttttgtca cctccaacaa catccgcgag 360 atcgagattg attataccgg aacagagcct tccagtccct gtaataaatg tttatctccg 420 gatgtgacac cttgcttttg taccattaac ttcacactgg aaaagtcatt tgagggcaac 480 gtgtttatgt attatggact gtctaatttc tatcaaaacc atcgtcgtta cgtgaaatct 540 cgagatgata gtcaactaaa tggagattct agtgctttgc ttaatcccag taaggaatgt 600 gaaccttatc gaagaaatga agacaaacca attgctcctg tggagctatt gccaacagca 660 tgtttaatga tacattagaa ttgtttctca ttggcaatga ttcttatcct atacctatcg 720 ctttgaaaaa gaaaggtatt gcttggtgga cagataaaaa tgtgaaattc agaaatcccc 780 ctggaggaga caacctggaa gaacggttta aaggtacaac aaagcctgtg aactggctta 840 aaccagttta catgctggat tctgacccag ataataatgg attcataaat gaggatttta 900 ttgtttggat gcgtactgca gcattaccta cttttcgcaa gttgtatcgt cttatagaaa 960 ggaaaagtga tttacatcca acattaccag ctggccgata ctctttgaat gtcacataca 1020 attaccctgt acattatttt gatggacgaa aacggatgat cttgagcact atttcatgga 1080 tgggaggaaa aaatccattt ttggggattg cttacatcgc tgttggatcc atctccttcc 1140 ttctgggagt tgtactgcta gtaattaatc ataaatatag aaacagtagt aatacagctg 1200 acattaccat ttaattttat attatgaaag caaatcatct gcatgtgcat caaggccagt 1260 cctattcaac ctagctttcg aatgctgata tctggttagt atgtcatttt gaagttggca 1320 cataactttt ctaaaaaaaa gcagtctttg ttgtttgctt cttccctacg gatgacttct 1380 aaaaatatat gacgggtata aaaaaattag ctatattgat catatcaaca ctgtaactgc 1440 tgaaatggca ttctaatgtt tgctttttat tcggacaggc cacatgatgc atagagcctc 1500 tttcatgtga cttgtgtcta ctgcttaaat ctttatgctg tgttgatgat attatattga 1560 catatgaagc tgtatatgtg tatgtatttt gtggagaaag ggattacaag atgtatgagt 1620 ataatgactt gctaaccttt caggattcag agaaagatga agaaagacca tatctaaata 1680 atacacttca tcattttcat gtgtataaat gcttaaagta ccatctttgt tgaggtggtt 1740 catgtatcca gtttatccag tacagttatt tgtcaagctt agctttgatt tcaaaggaca 1800 cgcttacctt gtctggcata agaattaatg ctcatgtctg cagtggttgg gtaggtcctg 1860 cttaggagaa ttaaaaaatt cctctttccg tttggttgaa tgttgcagtc aggaacccca 1920 actcacttgg aatgttttta tatgtaatca tttcccttga agcttatact ttataaggga 1980 agaaagaatt caggtgatat gggaaaactg cttggcagac cttcatcttc tgcctcaact 2040 gtaaaccaca tgtaaatgct taatggagac tgttttcatt cttgtgatat ttaacattca 2100 gaaaattact tcagctttgg aaatactcag gctgttttta ttctgcaggt aagtgttttg 2160 acttaagtac taatattcca gaaatttttg aaagcagtaa ccttaatttc ctatgtattt 2220 cattccactt ttgcatatag gtcaaatagc aatgtgtatg cacattctct ttagttaagg 2280 caccaattgt tttggttggt tttcctaaga catactttaa aaagatgttc tataaatttc 2340 ctagttaaat tatggggatt ttggagtatg tacatgataa attataatac gtatatggtt 2400 gaagttattt tattttttac taatgaatta ttttaatatt ccttattgaa taaatgctgt 2460 aacttgtttg ctatggaact tattcttaaa gttctagtta aaaataattt ttccacatgc 2520 atgaaaatat gtattaatca gaggtggctt aattacattg aaattgcttt tttgttgttg 2580 tttttttact gaaataactc atgtttgtgt agaagaatgc ctgtttactc agagtttata 2640 ttttccttca gttatatttt aaatcaaaag gtctgggtaa tgtatacttt tgattaatat 2700 atactttttt taaaaaacaa aaaacaatgt aatggttaat agtagaaatg tgccacactt 2760 ttcaagtttt atataacata tgaaattcag ttaaaagaat gtgtgtttca taatgacttt 2820 taactggtaa aaatattact tgcacgaagt aacttgatgt atggttatcc tgaaatttcg 2880 gagtatttgg tgtgttcttt gtctaaaaat agtctgtttt gtcagtcctt cagaatatta 2940 tttattctga agattgtccc tcttgcactt gggcagttta ttttcgggga tacattgttg 3000 ggggagaggg gtttctgcca ctctttccag attgagtctg tgctgtttaa ggaggactac 3060 catcctgcaa ctctttttct aattggggca cagaggatgt cgctaaagaa aagttgaaga 3120 gccctttcag cactttctca tctgtggaga agatggaatc ttaaaataca tttggagttt 3180 tatctgtttt acaagtccat tgatggccta agttcctcct gttttctgct gtttgatctc 3240 taaggaactc ctgttgctaa atatgaagag tatggaacat tcatatagtc tctgtgaagc 3300 atggggggag ggaagacatt tctttttctt ataggcttta tgctcaaatg tcatagtctc 3360 ctttcaaaga attgtgttgc attttaaatg cacccagctt aagtagaaga cattgaagga 3420 tgcattaatt ttcaggaact attttgaatt atgaaaagat tcccaattga aaaaattatt 3480 caacaagtaa aagctaagaa atttcattga aatcataagg cagtttaagc ataaattgat 3540 aaaaatagct gtgtactact aattaataga aaatcattca accaagagaa gagtcaagtg 3600 aatatcgttt gtttatttgc tagtgagttt ctttgtaacg ttgattttat taaatgataa 3660 tatttggtta gtatgtccta tgttaataaa aatgaacaaa attaattttg ctatgttcag 3720 gtgtcttgat aaaataacaa tgctccagtg ttgttgctta catttagcac taaattttaa 3780 cacagggtca gtgagtccag gttttaactt cttcatgcct ggatgggata aaatgtaatt 3840 cattgttaaa ttaattcata tttgtattta ttaatcactg tgaccaacat taaccatttg 3900 ttcttaccag gaagtggtca gattatcatc tgagttacag ttagactggc taagtttggt 3960 attagatcaa ggggaatgtc cagtaaacag agaggtaagc atgatggaaa taatgaagtg 4020 gggtacacag gaaaaacctg actagtgagg aggagcagct gagagatagg gtcagtgaat 4080 gtggttcagc ctgctacctc tcctgtcttc atagaaccat tgccttagaa ttattgtatg 4140 acacgttttt tgttggttaa gctgtaaggt tttgttcttt gtgaacatgg gtattttgag 4200 gggagggtgg agggagtagg gaagtggtcc ttttacaaga attttgatgc ataagtgtct 4260 attgtagggt ttggatgatc tagtaaagtg ttttagaacc cctttttatc ccatgcacca 4320 ttcagtaaac ataaaaatca caattctgct aatgtcattt ggaacttcaa aataaatatc 4380 ttgtctaaaa acaagaaaaa aaaa 4404 <210> 16 <211> 3150 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 252964.2 <400> 16 cctttctcct cacccagccc cttgctcttc ccttttgaaa ggcccgtgtg ttttctttcc 60 ttaccctgtg cttgctcatg tctactccgg ttttctctac cacatcctta gagccatcac 120 ctggcacgca ggcgccttac attctacggt agaacgtggg gtactgtgtg tgcacataga 180 cacacttacg tggaattaca gttgtgggtt tatccaagat gaggaagatt tcacctgctg 240 tttaatagac ttggggccat gtgcctcccc acacatgggc aaggacaggt ggaatgtcgg 300 gaccacactg tgcggcttct cggcacaaag cggagggagg ctgtggtcgc tgccggccta 360 ggtgtcccag gtgccccgcc tttctctggg acacagttgg gggctggctt ctgagggatt 420 cctttctccc ctctttgtgt ggccccagcc agggcggtgg gcagtcctgg tgtagagcac 480 aagcctctcc accctagaga aatgcctctg taccacggct accatgtgga accttaactt 540 gcagaaggct tgttaacaat tgttttgaga gagatggctg gtcatgccac agctgctggg 600 gactccgcct actccagccc tcttgggaca cactgtggga tttgtggccc ttccccagag 660 gaattgtgga gactgtccca tggaacaaac cctcaggcac cagcacaggg ctctgggtga 720 ctcagtaaaa ctaacgtttg tctctgacaa gatcagctgt aggctcaccg gccagagaag 780 accactgtga gcattttgcc gtatatcctg ccctgccatt tgttcacttt ttaaactaaa 840 ataggaacat ccgacacaca ccgtttgcat cgtcttctcc cttgatattt taagcatttt 900 cccatgtcat gagtttctca gaaacatgtt tttaacaatt gtactattta gtcattgtcc 960 atttactata atttatctga ccatttccct actgtaaaat acttaagacg gtttctgatt 1020 tttccactat ttaaataatg ctgtgatgaa tatctttaaa atcttctgat ttcttacttt 1080 tttccccctt agatgcctgg aagtggtatt ttgaggtgaa agagtttgtt cattttgaag 1140 atatttctgt ctctctctcg acctgatgtg tagacgctca cttccagtag cagaaccacc 1200 ttagttgtgt cttacagatt ctgaacaaat cggtttctga taagccatgt gttccaaaga 1260 atgtctgaat aagaccgctc tttatttaaa tgctaagagg atgtcactac tgcaatccat 1320 ctgtggccga ttttttccaa gagccaattt ccttgttttg gttgcaagaa cctggctctg 1380 cctgcatgtc agctctctgc cctccctgct gccgtggctt tcaagcgctt ggcagaatct 1440 tgtacttcgt gtccacaatg gtactgaatt tgcatctgca cagtcagcag agataacaag 1500 tgttgaactg accttgccac atgcttagtg agtgatttgt aattaagttt atagactcag 1560 aaggtatatt aggacatttg gaatcagtag cagagcaaag cctctttgaa'aaaaaccacg 1620 tagactgatt gggttttaca agagtgcatt tgtctccccc ttccaccccc ccaccttcag 1680 gtcttagtgg ttcacaagag cccagcagcc aggctggctt tttcattgta gggcgtggtt 1740 gtcccagctg gtgtagattt caggccgccc cccccaactc cctgcccaca gtgttgcaga 1800 ttgcctggct ggcagcaagt ccagaccacc caaatttggt tggattcttc atttctccac 1860 tgtagttggg gtccattgat tgtgcagggg aacgtgcagg aggtttttct aggcaccgtg 1920 ttcagtgctg cttcactcta ccagagatta tggccaaatt gcacggaatt tggtttcttg 1980 ccctctgaag cctgagggcc cccccttgcc tggctggttg acagacccgg ggtggtcact 2040 gctgagactt cagagatcgc agctgctgtg agaatacggt gaaggtactt tgttctggaa 2100 gatgttgtca tacacttttc cccagttatt ttcaaacttg acatgagcct atgttgactc 2160 actgggtggg ggtcccttct tacgcagcac acgtggcaag tgcctgaatc ggggctggag 2220 gcacttcaga gcctctgagg ggccaccact tctggcccaa aattgcaggg ttgtagatga 2280 ggctgcctgt ggagaactgg tgtgaggagg aagctgtttc caacaaagag cactttcatc 2340 tgttgagatg gctgtggtga gcaactgaac gagcctacgt gtgtacctga aattttcccc 2400 gtaactcatt tcttccatat gaagaaacac caaactatgt acagagaact ttttacaaaa 2460 gggcagacct tttttaagct gtgtaaccca catagcctaa ccacctggca gaatgactac 2520 gaataggggt cattgtgctg gtaaaagcct ctattacgac tgtaagtaag ttggatgttg 2580 gcaaaattaa attgttacag tatttagagc tgctgtagct gttccttcac aacataaaat 2640 aggataaatg actagtacgt ctttcaggtg ggtggcaagc agaacatgcg taatattctc 2700 tacctggtct gtagctgtaa ctgtgatgta cagacaaagc aaaaattaaa agaacttatg 2760 aaaacaaatg caatgatact aggatataca cttttgtatt tttattctta tataaggtta 2820 tttgctggct attgttggcc tctagttcag tctgtgttat ttaaattcta atatatgaat 2880 tatttgaatt gaattcatgt tcggggccac gttgttgtat gtattgatgt acagccttga 2940 atgtgaataa ttattgtaaa ctatatttta caactttttt tctggcttta ttatataaat 3000 tttctattgg gtcagtgatt taatcatata atttaatgaa tctgtttatc cttttttttt 3060 ttccaaatac ttgtgcttta ggtgtagtta ccagatgatg aattttcctc gtatggtcag 3120 tagtcttgta ataaaaagca tgtagagtgt 3150 <210> 17 <211> 1852 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 267153.7 <220>
<221> unsure <222> 551, 1151, 1200, 1257, 1823 <223> a, t, c, g, or other <400> 17 ccggcgccga ggttcttgac tgctgtgccg gacgccaggt gtagccatgc agcgagccga 60 ttccgagcag ccctccaagc gtccccgttg cgatgacagc ccgagaaccc cctcaaacac 120 cccttccgca gaggcagact ggtccccggg cctggaactc catcccgact acaagacatg 180 gggtccggag caggtgtgct ccttcctcag gcgcggtggc tttgaagagc cggtgctgct 240 gaagaacatc cgagaaaatg aaatcacagg cgcattactg ccttgtcttg atgagtctcg 300 ttttgaaaat cttggagtaa gttccttggg ggagaggaag aagctgctta gttatatccc 360 agcgattggt tcaaatccac gttgatacaa tgaaggtaat taatgatcct atccatggcc 420 acattgagct ccaccctctc ctcgtccgaa tcattgatac acctcaattt caacgtcttc 480 gatacatcaa acagctagga ggtggttact atgtttttcc aggagcttca cacaatctac 540 gagcttgata ntctaggggt ggggtatcta gcaggatgtc tagttcacgc actgggtgaa 600 aaacaaccag agctgcagat aagtgaacga gatgttctct gtgttcagat tgctggactt 660 tgtcatgatc tcggtcatgg gccattttct cacatgtttg atggacgatt tattccactt 720 gctcgcccgg aggtgaaatg gacgcatgaa caaggctcag ttatgatgtt tgagcacctt 780 attaattcta atggaattaa gcctgtcatg gaacaatatg gtctcatccc tgaagaagat 840 atttgcttta taaaggaaca aattgtagga ccacttgaat cacctgtcga agattcattg 900 atttggtgcc tatcctaaaa cttccagtgg gttttcttgc cttccagtgg ccatataaag 960 ggcgtcctga aaacaaaagc ttcctttatg agatagtatc taataaaaga aatggcattg 1020 atgtggacaa atgggattat tttgccaggg actgccatca tcttggaatc caaaataatt 1080 ttgattacaa gcgctttatt aagtttgccc gtgtctgtga agtagacaat gagttgcgta 1140 tttgtgctag ngataaggaa gttggaaatc tgtatgacat gttccacact cgcaactctn 1200 ggacaccgta gagcttatca acacaaagtt ggcaacatta ttgatacaat gtaaganact 1260 tgattgtcat ttccctataa aattttcctt gatacttggc tagagtatca tactaggctc 1320 aactagacat ttctagatga gttcaagtga atattaagtg attaaattga aaatggtttc 1380 cttaaagaaa aaaaatctag cataaagtta atttagttgg aggaaaagga gggaagtgga 1440 taaaggggca gatggaggga agtggataaa ggggcagatg aagggaagaa gagctggctt 1500 aggccagacg tgaagcggca gtgctgagat cactcaggac ctcggcacag gtagtcactt 1560 acacaccatt ctcatcagga gaatgggagg taggacatga atatttaaat tctgagatta 1620 atgacaaaag ttaactttaa ggattaagat taatgtctat ttgtatcctt tcaaatattt 1680 atcaaaatta gtaccaaatg gtaaaaccaa caggaatttt acctcttcct gacccagtca 1740 gaaccatagc agaaaactgt acagccaggt ctctccgtga ctcaaagatc cataaggagt 1800 tatcaaacac tgggtgtgag tcnagttact tcttccatgt ctctaaaata gc 1852 <210> 18 <211> 1513 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 331244.6 <400> 18 ggtaaagtgg cttctgggcg gaaggtacac tataggctcg gggaggtaag cggcggcagg 60 ccggcggttg gtgtgtcccg ggtgtgggga ggcgacagag ccctggcact tgagggttga 120 gggggcctcc ccagccgcgg cgaaaccgtc tagcctccgg aggccaggcc gtgagtgcgg 180 gaggtatacg ccaaggcgga agaattttgc cactcactac ctgtgtgacc tcgggtaaat 240 tagccttgga acgtcagttt cttcgtctct ataattgaaa taataatagt acctctctca 300 ggattgttgt gagccgtcag tgaaacactt agagcagttt ctggcacatg gtagaattgg 360 gctatttgct gaagcttctt ggtggccctt gctagcccag gaagaaactt acattttgat 420 ttttttgtac catggctttg gttcacaaat tgctgcgtgg tacttatttt ctcagaaaat 480 tctctaagcc aacttctgcc ttgtatccat ttttgggtat tcgctttgca gagtattcca 540 gtagtcttca gaaaccagtg gcttctcctg gcaaagcctc cctcacagag gaagactgaa 600 ggggatttgc aaggagatca ccagaaagaa gttgctttgg atataacttc ttctgaggag 660 aagcctgatg ttagtttcga taaagcaatt agagatgaag caatatacca ttttaggctt 720 ttgaaggatg aaattgtgga tcattggaga ggaccggaag gccaccctct gcatgaggtc 780 ttgctggaac aagccaaggt tgtctggcaa ttccggggga aagaagattt ggataagtgg 840 acagtgactt ctgataagac gattggaggc agaagtgaag tgtttttgaa aatgggcaag 900 aataaccaaa gtgcactgct atatggaact ctgagctctg aggcgcctca ggacggggag 960 tctacccgaa gtgggtactg tgcaatgata tccaggattc caaggggtgc ttttgagagg 1020 aagatgtctt acgattggtc ccagttcaat actctgtatc tccgtgtacg tggggatggt 1080 cggccttgga tggtgaatat caaggaggac acagatttct tccagaggac gaatcagatg 1140 tatagttact tcatgttcac ccgcggggga ccctactggc aggaggtcaa gattcctttt 1200 tccaaatttt tcttctctaa tcgaggaaga atccgggatg ttcagcatga gcttccgctt 1260 gataagatct cttctatagg attcaccttg gctgataaag tggatggtcc attcttcctg 1320 gagatagatt ttattggcgt gtttactgat ccagctcata cagaagaatt tgcctatgaa 1380 aattctccag agcttaaccc aaggcttttt aaataaagat catatggtag ttttgtttta 1440 ctaatctaag ggtactagca tctacaatga tatagacaaa ataaaatatt tctttaatgg 1500 catccaacca aaa 1513 <210> 19 <211> 3243 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 335484.1 <220>
<221> unsure <222> 3222 <223> a, t, c, g, or other <400> 19 gagggagagg ccgagagaaa tttcggtact gcgcatgaac cgagcgtgac gttgaggttt 60 gaaataaccg gcaaagagta aaggctgaaa ctagcttcct gaaagcttcg tagggcccga 120 gccctgtgag cccaggttct gcgcccacta ggaggtgtca tgctgactgc tttttttaaa 180 gccctagaat cttggcttcg gcgtttgggg taagctccgt tctcgttctc aagcgcgttt 240 ccgcgaactc tcgcgggatt gacgggccgt ctcgagagcc ggcatctcct aggagctagt 300 cctggtcctc ggctaggcgg cttggggtcg cggcgtaact ggggagccag cctgacgccg 360 gcggaccccg cctgtgatcc tggcaacgat ggatgatgac ttgatgttgg cactgcggct 420 tcaggaggag tggaacttgc aggaggcgga gcgcgatcat gcccaggagt ccctgtcgct 480 agtggacgcg tcgtgggagt tggtggaccc cacaccggac ttgcaggcac tgtttgttca 540 gtttaacgac caattcttct ggggccagct ggaggccgtc gaggtgaagt ggagcgtgcg 600 aatgaccctg tgtgctggga tatgcagcta tgaagggaag ggtggaatgt gttccatccg 660 tctcagcgaa ccccttttga agttgaggcc aagaaaggat cttgtagaga ccctcctgca 720 tgaaatgata catgcctatt tatttgtcac taataacgac aaagaccgag aagggcatgg 780 tccagaattt tgtaaacata tgcatcgcat caacagcctg actggagcca atataacggt 840 ataccatact tttcacgatg aggtggatga gtatcggcga cactggtggc gctgcaatgg 900 gccgtgccag cacaggccac cgtattacgg ctatgtcaaa cgagctacta acagggaacc 960 ctctgctcat gactattggt gggctgagca ccagaaaacc tgtggaggca cttacataaa 1020 aatcaaggaa ccagagaatt actcaaaaaa aggcaaagga aaggcaaaac taggaaagga 1080 accagtattg gccgcagaga ataaagataa acccaacaga ggtgaggccc agctagtaat 1140 cccttttagt gggaaaggat atgttctagg agaaacaagc aatttacctt cacctgggaa 1200 actgatcact tcacatgcca ttaataaaac ccaagatctt ttaaatcaaa accattcagc 1260 aaatgctgta agacttaatt ctaaaatcaa ggtgaaattt gaacagaatg gttcaagtaa 1320 aaattctcat ctggtctccc ctgctgttag taacagtcac caaaatgttc taagcaacta 1380 ctttcctaga gtatcatttg ccaaccaaaa ggctttcaga ggtgtgaatg gatctccaag 1440 gataagtgta acagttggca acatccctaa aaactcagtc tcttctagtt ctcagagaag 1500 ggtttcatct tctaagatat ccctaagaaa ttcttcaaaa gtaacggaat cagcatctgt 1560 gatgccatcc caggatgtga gtgggtctga agatacattc ccaaataaac gacctaggct 1620 agaagataag actgtttttg acaatttttt tatcaagaaa gagcaaataa aaagcagtgg 1680 taatgatcca aagtatagta caaccacagc tcagaattcc agcagttcat ccagtcagag 1740 caaaatggtt aattgcccag tttgtcagaa tgaagttctg gagtctcaga ttaatgagca 1800 cttggactgg tgccttgaag gtgacagcat caaagtcaaa agcgaagaaa gtctttgaaa 1860 aaggtttcaa agtctcaagt accacctgta ttatctcact aatgtgctat gtcagccagt 1920 caggaagttc tggttaatac taagatttgt aggttataat ctagttcaca taaccaatag 1980 aaagtgtcct attttatata tacgcatata agattgtaat tttaagatgt tttgtgtctc 2040 agggtgctac attcactctt gccttaggta tactgtaacc caggttctgc ctgtcgtgta 2100 taatttttag atacttttgt tctttcttgc tcttaaggat tttaaaaacc tgttaatctt 2160 tttatttgta tactttccta aaaatattca tatggggaat cctgtcaggt gtttggttat 2220 attgactatt tattaatagt attagaactc attccctgaa ctgatgtaaa tcttcatagt 2280 gtcagacata ctgaccaaaa ccacaatcta gactacaaag tatattgttt tagagtactc 2340 aaattgtatt atttattaat ttttttgttt gcaaaatctt aacaggaact gtattttcta 2400 tattttaaag aattttattt gtcccacttt tactaaacag tggcagcaga ttttaagtta 2460 aagaatatgg aatatagtaa aataagtaaa tttcttttgg aatattttta gtaacaaata 2520 gccactataa ttctgtaggc caaattttat attgagttta gctgttttct caaaatttag 2580 cagagtggtt aaaattctgt gctgataagt aactgataca tataacataa acataacaaa 2640 gttgcctagt tgatgtaaca gtggaaagtt atctggaaat agtattttga actttaagcc 2700 aagtttaaaa cattataata aaaggaatac catttgtgca ttttaagtaa tcttttttaa 2760 aaaaaatatt ttccatgtta tagggaaagg acaaagagac ttttatcagt ttgctttttg 2820 tcttgtggct gtacatgctg ttggcatagc cctaatacag ttgttcacaa gttttctttt 2880 ttcttgttgc aattttcctt cactttgttg taatacaggt gcacaaatct taagtgcaca 2940 gctgggtaaa cttttacagt gttcacctgt gtaactacca cccggatcaa gttagagaac 3000 acttccattg ccacagaagg cttcctatag gtgtctgttc ccagttgata cccatgaccc 3060 tcaccacctc cagaggtccc cactgttttc accccatcgt cgcagattat tttttaattt 3120 tataatgtag tatctttgtt cctatgtata gcaggagttc attttcattg ctcttgcatt 3180 tgtatgaata tactagaatt tattcatcat ctatgtaatg gncattgaat attccagttt 3240 ggg 3243 <210> 20 <211> 1451 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 337489.2 <220>
<221> unsure <222> 281, 291, 830, 845 <223> a, t, c, g, or other <400> 20 acagtggcgt gttcctagaa gccgctttcg gcatcagtag gcggcggcgt ggggtctggc 60 agcgtgggga gagggaccaa ccgacgccac ttcgtgttgg gaagtgggag cgggagggcc 120 gggcaattcc cgaccgaacc aaacggtttc catggatctc aatagtgcca gcactgttgt 180 tcttcaggtg ttaacacagg ccaccagtca ggatactgct gtgttaaaac cagctgagga 240 gcagttgaag cagtgggaga cacagccagg tttctattca ntgttgctga ntattttcac 300 caaccacact ttggatataa atgtaaggtg gcttgctgta ctgtatttta aacatggaat 360 tgatcgctac tggagacgtg tagcacctca tgctctctca gaggaggaga aaactactct 420 gcgtgcaggg ctcatcacca acttcaatga accaataaac cagattgcaa ctcagattgc 480 agtgctcatt gcaaaagttg ctagattgga ttgtcccaga cagtggcctg aactaattcc 540 cactcttata gagtctgtta aagtccagga tgatcttcga cagcacagag cattacttac 600 cttctatcat gttaccaaga cactggcatc taaacgactt gctgctgata gaaaactatt 660 ttatgattta gcttctggaa tttataattt tgcctgctct ctgtggaatc accacacaga 720 cacattcctg caagaagttt cttctggcaa tgaagctgca attttgagtt cactagaacg 780 aacactgcta tcattgaaag tgctgcgtaa gttaactgtt aatggatttn tggacctcat 840 aagantatgg aggtgatggg ttttttacat ggaatatttg aacgtctaaa acagtttctg 900 gaatgcagta gaagtatagg tacagataat gtgtgtagag atagactgga aaagaccatc 960 attcttttta ctaaagtgct tttggacttc ttggatcagc atcctttttc atttactcct 1020 ctaattcaga gatcactgga attttctgta agctatgttt ttacagaagt tggtgaaggc 1080 gttacatttg aacgattcat tgtccaatgt atgaatctta ttaagatgat tgtcaaaaat 1140 tatgcttata agccatccaa aaattttgaa ggtaattcct ttattggcag tttaaaagaa 1200 ttattttaat cttaagtgtg atataattgc tataattaca aactttttaa aaaatgtcat 1260 tttagtctga aaaataaatt gttgctggga catgaaaaag atataaggat tataggcttt 1320 agtatgttta tactagcttt taaaaacaac atagtgcatt taataagcca ttttttgtag 1380 cacaaattgg ttgaagctta gggactttaa gaattaggta ctatagtcat cactgcagct 1440 catattgtag g 1451 <210> 21 <211> 2710 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 359574.5 <400> 21 ccacgctgct gcatgggcca cgtgagctca ggctgtggga gcggatggag ctgctacagt 60 cagcgcttgg ggctggcctc agcttgtaga cccgagccct gcagaacaac cccccgtggc 120 gcaggagagc agaagaaagg gggcctttat gcccttttga gggaagcaca cattctgcaa 180 ggccgtggaa acaaagggag gaactgtttg tagccctcgt ccagacgccc caaacaaaca 240 gagccaagtt acaccctgtt taaccctgcc ttcaaaggga cgactctgta agattctctg 300 ctacttattc aagttgacac gatgcccttc acactccacc tgaggtcccg ccttccctct 360 gccataagga gtttgattct acaaaagaaa ccaaacatca gaaatacatc cagcatggct 420 ggagagctcc gaccagccag cctggtggtc ctgcccaggt cccttgctcc agcttttgaa 480 agattctgcc aggtcaacac tggtcctcta cccctgctgg gccagagtga gccagaaaag 540 tggatgctgc cccctcaagg tgctatctca gagaccagga tgggccatcc ccagttctgg 600 aaatacgagt tcggtgcctg caccggcagc ctggcttcgc tggagcagta ctcggagcag 660 ctgaaggaca tggtggcctt cttcctgggc tgcagcttct ccctggagga ggccttggag 720 aaagcggggc tcccccagaa gagacccagc aggtcacagc caggcgggtg catacaagac 780 aacagtgcct tgtgttaccc atgctggctt ctgctgccct ctggtggtca cgatgaggcc 840 cattcccaag gacaagctgg aagggctggt gcgggcctgc tgctccctcg gaggtgagca 900 ggggcaacct gttcacatgg gcgacccaga actgttggga atcaaagagc tttccaaacc 960 tgcctacggg gatgccatgg tgtgtccccc aggggaggtt ccagtgttct ggccttctcc 1020 gctgaccagt ctcggagctg tcagcagctg tgagacccca ctgggctttt gccagcatcc 1080 caggctgcac agttatgact gacctgaagg atgcaaaggc tccacctggt tgtctcaccc 1140 cagagagaat tccagaggtc catcacattt cccaagatcc tctgcactac agcatcgcgt 1200 acagtctctg cttctcagaa gatcagagaa ctagagtcta tgatcggcat agacccaggg 1260 aaccggggga ttgggcacct gctctgtaaa gatgagctgc tgaaggcctc tctctcgctg 1320 tcccatgccc gctcagtgct catcaccact gggttcccca cacatttcaa tcatgagcct 1380 ccagaagaga cagatggccc accaggagct gttgctctgg ttgccttcct gcaggccttg 1440 gagaaggagg tcgccataat cgttgaccag agagcctgga acttgcacca gaagattgtt 1500 gaagatgctg ttgagcaagg tgttctgaag acgcagatcc cgatattaac ttaccaaggt 1560 ggatcagtgg aagctgctca ggcattcctg tggcaaaaat ggggacccgc agacacctag 1620 atttgaccac ctggtggcca tagagcgtgc cggaagagct gctgatggca attactacaa 1680 tgcaaggaag atgaacatca agcacttggt tgaccccatt gacgatcttt ttcttgctgc 1740 gaagaagatt cctggaatct catcaactgg agtcggtgat ggaggcaacg agcttgggat 1800 gggtaaagtc aaggaggctg tgaggaggca catacggcac ggggatgtca tcgcctgcga 1860 cgtggaggct gactttgccg tcattgctgg tgtttctaac tggggaggct atgccctggc 1920 ctgcgcactc tacatcctgt actcatgtgc tgtccacagt cagtacctga ggaaagcagt 1980 cggaccctcc agggcacctg gagatcaggc ctggactcag gccctcccgt cggtcattaa 2040 ggaagaaaaa atgctgggca tcttggtgca gcacaaagtc cggagtggcg tctcgggcat 2100 cgtgggcatg gaggtggatg ggctgccctt ccacaacacc cacgccgaga tgatccagaa 2160 gctggtggac gtcaccacgg cacaggtgta accgtccatg ttccgtgtga gcagagtccc 2220 taccaacggg caggtctgca tccggggaga atgcagctgc ttctggcgac aatcctgcta 2280 gtaaacactg gtcttcggtg agcaacgaac actcgcctgg cctgggaaac tgcatgccca 2340 ctttctggga ggggttagtg caggtgccgt ggacaaagga caacatttct ctggggcttt 2400 ttaactttta ttcctaagac tctaaaggcg ttgatttcaa ccctccttca ctctggcttc 2460 ttcaggcaac ccacgtggtc tcctgtgaga atcttctcga cagttactta tggggacact 2520 tgtgaacaat taactgccag gcagagcatg agaacaaaca ttcccaggcc atgtaggata 2580 ggatactcca gactccagtc atcctccccc atccatggtt tctgttactc atggtttcag 2640 ttactcatag ccaactgcag accgaaaata ctaaatgaaa aatttcagaa ataaacaact 2700 cttaagtttt 2710 <210> 22 <211> 2271 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <223> Incyte ID No: 360645.5 <220>
<221> unsure <222> 2002 <223> a, t, c, g, or other <400> 22 cggaggcgag cggagggttt cccgcggcgg atttctgaca gtcagacttg tccacaagaa 60 ctcaactggc aaggctgctt ttctgtgcta aaactgggga gctagtgggc accatgaaga 120 tcttctgcag tcgggccaat ccgaccacgg ggtctgtgga gtggctggag gaggatgaac 180 actatgatta ccaccaggag attgcaaggt catcttatgc agatatgcta catgacaaag 240 acagaaatgt aaaatactac caaggtatcc gggctgccgt gagcagggtg aaggacagag 300 gacagaaggc cttggttctc gacattggca ctggcacggg actcttgtca atgatggcgg 360 tcacagcagg tgccgacttc tgctatgcca tcgaggtttt caagcctatg gctgatgctg 420 ctgtgaagat tgtggagaaa aatggcttta gtgataagat taaggttatc aacaagcatt 480 ccaccgaggt gactgtaggt ccagagggtg acatgccatg ccgtgccaac atcctggtca 540 cagagttgtt tgacacagag ctgatcgggg agggggcgct gccctcctat gagcacgcac 600 acaggcatct cgtggaggaa aattgtgagg ccgtgcccca cagagccacc gtctatgcac 660 agctggtgga gtccgggagg atgtggtcgt ggaacaagct atttcccatc cacgtgcaga 720 ccagcctcgg agagcaggtc atcgtccctc ccgttgacgt ggagagctgc cctggcgcac 780 cctctgtctg tgacattcag ctgaaccagg tgtcaccagc cgactttaca gtcctcagcg 840 atgtgctgcc catgttcagc atagacttca gcaagcaagt cagtagctca gcagcctgcc 900 atagcaggcg gtttgaacct ctgacatctg gccgagctca ggtggttctc tcgtggtggg 960 acattgaaat ggaccctgag gggaagatca agtgcaccat ggcccccttc tgggcacact 1020 cagacccaga ggagatgcag tggcgggacc actggatgca gtgtgtgtac ttcctgccac 1080 aagaggagcc tgtggtgcag ggctcagcgc ttctatctgg tagcccacca cgatgactac 1140 tgcgtatggt acagcctgca gaggaccagc cctgaaaaga atgagagagt ccgccagatg 1200 cgccccgtgt gtgactgcca ggctcacctg ctctggaacc ggcctcggtt tggagagatc 1260 aatgaccagg acagaactga tcgatacgtc caggctctga ggaccgtgct gaagccagac 1320 agcgtgtgcc tgtgtgtcag cgatggcagc ctgctctccg tgctggccca tcacctgggg 1380 gtggagcagg tgtttacagt cgagagttca gcagcttctc acaaactgtt gagaaaaatc 1440 ttcaaggcta accacttgga agataaaatt aacatcatag agaaacggcc ggaattatta 1500 acaaatgagg acctacaggg cagaaaggtc tctctcctcc tgggcgagcc gttcttcact 1560 accagcctgc tgccgtggca caacctctac ttctggtacg tgcggaccgc tgtggaccag 1620 cacctggggc caggtgccat ggtgatgccc caggcagcct cgctgcacgc tgtggttgtg 1680 gagttcaggg acctgtggcg gatccggagc ccctgtggtg actgcgaagg cttcgacgtg 1740 cacatcatgg acgacatgat taagcgtgcc ctggacttca gggagagcag ggaagctgag 1800 ccccacccgc tgtgggagta cccatgccgc agcctctccg agccctggca gatcctgacc 1860 tttgacttcc agcagccggt gcccctgcag cccctgtgtg ccgagggcac tgtggagctc 1920 agaagctcag gaagatggga gcttacttcc tgtggtcacc gatgcaccat tttcctgaac 1980 cctcctggga gctggagcag gnccgggcag agccacgcag cggtgctatg gatggagtac 2040 cacctgaccc cggagtgcac gctcagcact ggcctcctgg agcctgcaga ccccgagggg 2100 ggctgctgct ggaaccccca ctgcaagcag gccgtctact tcttcagccc tgccccagat 2160 cccagagcac tgctgggtgg cccacggact gtcagctatg cagtggagtt tcaccccgac 2220 acaggcgaca tcatcatgga gttcaggcat gcagataccc cagactgacc a 2271 <210> 23 <211> 2611 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 404145.7 <400> 23 gctgtggggt ttttctgtaa gactgaagat gacttcaatg attggtgcca gcaagtcaaa 60 aagctgtctc tgctcggagg tgccctgccc atgtttgagc tggtggagca gcagccttca 120 catctgggcc tgccccgacg tcctgaacct gtccctaggt gagagctgcc aagtccaggt 180 ggggtccctc ggaggtacga tctgtgccct tgcttcccca gtcctggccc ccttggtttt 240 gaccattaag gtgtgtgtga gcctgagccg tgagcacttg gcagtggttc gcctgtgaga 300 ccaggtatgg agtggagcgt cccctcctcc aagcttgcgc ccagcagccc aggacccacc 360 tcgtcttccc caccagcgct gcctgcccgg gcgctgtgga gctgggcgtg ctaccatgga 420 gtcctcaggg gtctggagca gacagaacat gcaggctctg tggtgacgca gtcctgggtg 480 ggggactggt tcacttgggc accactggcc atgggtggcg tagacccctc ggaccatggc 540 cagcgtgccg caggagccgg cctgggctcg tgcagtgaag tgagtggccg tgagcgcgtc 600 ctcctcatct ctgtctccct gtgggaaact ctacaaacaa ggcaatggca atggaaccac 660 tcctgatgac cacgagggtc agacgcggga cagaggcccc tcagggcctg agattgtgcc 720 ggccgccccc tgccctcctc accctgccct gctcctcttc tctgctccct ccccccatat 780 tcgcaggtct gcacaacccc cggacctgtt cacacccgca tggggacagc tgtctgtggg 840 ctgcagagca ggcactgctc agtctgcccc acgccaaggg cccttgactc acacccaggt 900 ggcccaccca agatgcctga tgcgctatgt cctgttcctt ctagattctt ctgatgtaga 960 gcgactggaa agattcttcg actcagaaga tgaagacttt gaaatcctgt ccctttgaaa 1020 atcctggggt cgggggtggc acctgtgaga gcctggggct cctggtgccg ctgcgtttca 1080 tccatcccgc ccgctcgcct gccgagggct gcgccccgtg ctgcctcccc ccagagggcc 1140 acccgctgtg ctcgtggact gaggctgcgc tgcccgggag gccttactgc ttggtgtcag 1200 actgcccagc tcagagtgcc cgtcagggcc tgtgcatccg cacgcggagc cgtctgttag 1260 gagcttccag agtgttctct cgacactgcc agccccgtgt tagcacctgg gcctcagtcc 1320 cacttgctcc caggcgccgg ttctgtggtt ggtttggaat taaagtcctg tttgaagttg 1380 tcagacacag acatgaattt ctggggcgct ccctgagtca gagtctcaga agacctgtgc 1440 aggctggcgt gagaggagcg gcagccacac tgcggcccca cgcccaagga ctgggctgct 1500 ctcgaggggg gcgcgcccac cgctgtgtcc tctctgccca gcctggctta ccaagggcta 1560 cctcagtggg agatgaggtt ggaggaacga aggcgaggtt cctccttgct ttggggagaa 1620 aagtattcag gaagtgggtg tgtgggaaac ctgaagatgg cgtgcacagg acacagcgtg 1680 ggcggcctgg gcagaagggc ggctggctgt cctggagctg ctgctggagc ctgccctcag 1740 agtgtccctt tccagtgctg tggcattctg tggcagcttc cccaggtgtg gtgacggggg 1800 ggggcggggc ctccacctgt gacagccagg cttgagggtg gacggcgtgc ctctcccagg 1860 agccttcccc atgtccttgc cttgctgaga attgccctcc catgccgctg aggtgttagg 1920 tggtttaggg ccaaaagggg aaaaccactt gagtcttgtg gtgtgtggtg ggcagacacc 1980 acagggtggc atcacctggt ggcatttcca gaacctcagc cccgattcca gcacccacca 2040 ccgcctgacc ctgtgtaacc tgctgtcccg ggtcccagag tgcactctgc cccgctgctc 2100 tgctgcctgt cctgggaaag tagctttgcc ccactaggaa atgtaaacag gagggcttgg 2160 ggagcgtggg cacttttctc atgagcagct actgcggcgt tggcaggact cgctgctgct 2220 gctgctgctg cttgtgtagg tcggggagcc ggagatcccc gaggacgcgc gccggacagt 2280 cggcactgac cggcccacct ggtagcagag gacaccccca gccccccaag cattgaagac 2340 atagtgtatt tcctcgtatc ctttctccct tgggtgtagt tggggtgggg aagcagggaa 2400 ggctggtgcg atctccattc cttgggctcc acgtccgagt tcatggtgcg ccgctgtgct 2460 gggagctgca gtggtaatgt gtgggacacc ttgaccaaag gggagctttg tctcgtgtgt 2520 tttgaaaaag gcttaatgaa gagaatgttg ttcattctta gtagtatagt ttgcaattct 2580 taatggcaaa taataagttt cagtagaaaa c 2611 <210> 24 <211> 1331 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 480119.1 <220>
<221> unsure <222> 605, 733, 1319, 1325 <223> a, t, c, g, or other <400> 24 gagaaagctt aatattgaag tatctctcct atgaggtgtt agaactattt gcctacaatt 60 tattggggaa aaaattgctc atttgtgtac ataaacctag gacagagcac atagggaaaa 120 taacattcca acacagggga attttgccca aggctcatga aagaacccaa gccagttttc 180 tcaagacttg acctcaggcc tactggaata.tttctctcaa agtctcctgt tctcacactg 240 acaagactga tgtccctgtg ttaggattgg acagaggaat gtttctgtgt gcaaggaaga 300 actgcttaat gtaagagggc ccatctgaat ttatttgcag gacatcggtg ggatcaagtg 360 aaaaaggagg accacgaggc aacaggtccc aggctcagca gagagctgct ggatgagaaa 420 gggcctgaag tcttgcagga ctcactggat agatgttatt caactccttc aggttgtctt 480 gaactgactg actcatgcca gccctacaga agtgcctttt atgtattgga gcaacagcgt 540 gttggcttgg ctgttgacat ggatgaaatt gaaaagaagg ggaagaagat caaagaagga 600 aagangaagg ggaagaaaag aaggggaaga agatcaaaac ccaccatgcc ccaggctcag 660 cagggagctg ctggatgaga aagggcctga agtcttgcag gactcactgg atagatgtta 720 ttcgactcct cangttatct tgaactgcct gacttaggcc agccctacag cagtgctgtt 780 tactcattgg aggaacagta ccttggcttg gctcttgacg tggacagaat taaaaaggac 840 caagaagagg aagaagacca aggcccacca tgccccaggc tcagcaggga gctgctggag 900 gtagtagagc ctgaagtctt gcaggactca ctggatagat gttattcaac tccttccagt 960 tgtcttgaac agcctgactc ctgccagccc tatggaagtt ccttttatgc attggaggaa 1020 aaacatgttg gcttttctct tgacgtggga gaaattgaaa agaaggggaa ggggaagaaa 1080 agaaggggaa gaagatcaaa gaaggaaaga agaaggggaa gaaaagaagg ggaagaagat 1140 caaaacccac catgccccag gctcagcagg gagctgctgg atgagaaagg gcctgaagtc 1200 ttgcaggact cactggatag atgttattca actccttcca gttgtcttga acagcctgac 1260 tcctgccagc cctatggaag ttccttttat gcattggagg aaaaacatgt tggcttttnt 1320 cttgncgtgg g <210> 25 <211> 2813 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 480951.5 <220>
<221> unsure <222> 13, 981, 992, 2807 <223> a, t, c, g, or other <400> 25 cctggagact cgngtggccg aggggcttca taccagctga agagcgacaa gccgctggca 60 gccgcggatc tcaccgccgc tcaggagatc tgttggtaat ctgaggattt ttattctacg 120 tcgtcttgac agatggaaaa cctgaagtaa cttcgggcta accttgtgtt tttggaaaat 180 tagtagactt ggtggtgaag aaactgggag gagtaggata ttagctaact ttgcatagcc 240 acatatagag cgtcgcagct gcattccacc aaagaggaac caaaaggcct gtggtgttcc 300 cagggtacat attcatgcca gaagtgaagt gccttggtga attcgtttcc tgaaagttta 360 tcgcatactt gtactgggtt agccttatgc cagcctggac catcttggag gcagtgtagg 420 atcatggaag aactttgaat taggttttta gaacttcagc cataaaaatg ggcagaattt 480 tccttgatca tatcggtggt acccgtctgt tttcttgtgc aaactgtgat acgatcctga 540 ccaaccgctc agaactcatc tccactcgtt tcacaggcgc cactggcaga gcatttcttt 600 ttaacaaggt agttaacctg cagtacagtg aagttcaaga tcgggtcatg ctcactggcc 660 gccacatggt tcgagatgtg agctgcaaaa actgcaatag caaactggga tggatctatg 720 agtttgccac tgaagacagc cagcgatata aggaaggccg cgtgatcctg gaacgtgctc 780 tagttcgaga gagtgagggc tttgaggagc atgtaccatc tgataactct tgaagataca 840 gagagaaatc catcttttcc caggtctcct tcactgaaaa caaaaatcta cttacataca 900 ctgtcacctt agcatcagag tcggattaat gaactgcgga acaagaggtt gtgagaatct 960 aagatggaac ctttctttct ntctttcttt tnttttaaat tttgtatttt ccatccaaca 1020 gcagtgtgta gagagaatat tatgcagatg ccgttaattt tttaccctat gtttacgtct 1080 tgaggcagca gagtctgtct gcagctatgt ggtgagctat gtaaggaaaa aaatctgggc 1140 tgttagagtg aaaaagtgtg ttttatgtca attgtgaaag gaaaatgtta ggagtatggt 1200 ttttaaactt gggcttcatt ttaaactttt ttttttaaac ccagttattt cacttgattt 1260 gctagcttca gagaagagat ccgaatctgt gcccagcgct aaaggctcag tgttagcatg 1320 gcttgtgctg gccggtgtgc catattcttg ttggagatga accgtagcac cagagcccat 1380 tcttccttgt cagtcttggc ccaaagatgt caccattcct agttatttgt caccacataa 1440 ttggtgttga ttggaaactt tttctgagat gggacagaac tgctgggttg tctttttcca 1500 tgtaacttaa gcatagtaat ataaataaag taatagttgg atgcttttgg tcctgtgttg 1560 cttttaaaaa caccttataa aagaggagag tatttgataa gcaattttca tagtagtaaa 1620 gttttttttc atctcttaaa ctaaattgac catgcatata atattctttg tttaaatgaa 1680 agcatactgt tgaaacccgc agtgttgcat ttagaaaaca gttgaacaga atgtcaatgt 1740 gcattcatgc aaaaaaacat ttaatctgca tctgttttag aaaaggggga aatgaagcaa 1800 cttgtctaaa aatactgctt tacaaagcat ttcagccttt ccccctcagt tttgcattga 1860 ttttttgaca agtctgtaga gcctaatagt ttccatcaaa ggcctagatc tcttatttag 1920 catttttttc agctcttctc tcagaagttc agctgttgaa acgaaaactg tactttgtac 1980 cctcacatac aaagggatca aatttgacct ggtgttattt tagccccaaa tttatgacat 2040 tacacaatat taaaatgtaa atgtttcttt acccaaacta cttctagata ttctagtatt 2100 tgcttctggt ggaattaaat gacggtaaaa ttggctaatt atttgaatga atgaatggat 2160 ggatgttttg catgctcaat ttctaggtcc tttgtctaga aaggaaattt gcctcagttg 2220 aattagtgaa atatttctgt cgttgatatt aaaagtgact tctgagtaca gttaagttcc 2280 tcctatttgc cactgggctg ttggttagaa gcataggtaa ctgattaagt aggtatgata 2340 ctgcatttga aataagtgga cacaaactat cctttctcca ccatggactc aatctgagaa 2400 caacagcatt catttccatt catttccata ctggcttttg attatatgca gattcctagt 2460 agcatgcctt acctacagca ctatgtgcat ttgctgtcac aataaagtat attttgtctt 2520 gcattgatgc agtactgctg cttattttcc actgatcttg tctagtgatc atcttaattt 2580 ttatctctga acacatactt ggtatctttg agtacctgta gctttcttca tttggcaatg 2640 atagtgatgt ctgacttgat taactgccta attcacacat gaagacattg actttgccag 2700 tattaacttc tctgagatca ttttgcctta gatactgata actatagttc agtatatata 2760 aacaaaaaaa tttcatatta ctaggttaac ttttaggtaa ctggcangta cca 2813 <210> 26 <211> 3281 <212> DNA
<213> Homo sapiens <220>
<221> misc_feature <223> Incyte ID No: 481257.3 <400> 26 cagcgacgac gcggaggcag agaaaggaac gcccggccca gccccgtagc acaggcggag 60 tgcagcggag ggcccctgcc gctgccgtca tgccgttccc gtttgggaag tctcacaaat 120 ctccagcaga cattgtgaag aatctgaagg agagcatggc tgttctggaa aagcaagaca 180 tttctgataa aaaagcagaa aaggctacag aagaagtttc caaaaatctg gttgccatga 240 aagaaattct gtatggcaca aatgaaaaag agcctcagac agaagcagta gctcaacttg 300 ctcaagaact ctataatagt gggctcctta gcaccctggt agctgattta cagctcattg 360 actttgaggg caaaaaagac gtggctcaaa ttttcaacaa tattctcaga agacaaattg 420 gtacgagaac tcctactgtt gaatacatct gcacccaaca gaatattttg ttcatgttat 480 tgaaagggta tgaatctcca gaaatagctc taaattgtgg aataatgtta agagaatgca 540 tcagacatga accacttgca aaaatcattt tgtggtcgga acagttttat gatttcttca 600 gatatgtcga aatgtcaaca tttgacatag cttcagatgc atttgccaca ttcaaggatt 660 tacttacaag acataaattg ctcagtgcag aatttttgga acagcattat gatagatttt 720 tcagtgaata tgagaagtta cttcattcag aaaattatgt gacaaaaaga cagtcactga 780 agcttctcgg tgaactacta ctagatagac acaacttcac aattatgaca aaatacatca 840 gtaaacctga gaacctcaaa ttaatgatga acctgctgcg agacaaaagt cgcaacatcc 900 agtttgaggc ctttcacgtt tttaaggtgt ttgtagccaa tcctaacaag acgcagccca 960 tcctagacat cctcctcaag aaccaggcca aactcataga gttcctcagc aagtttcaga 1020 acgacaggac ggaggatgag cagtttaacg acgagaagac ctatttagtt aaacagatca 1080 gggatttgaa gagaccagct cagcaagaag cttaatctcc aataaacatc tatgttaaat 1140 ccaaattcag catttgctgt tagctattca gcatcaggca ctcttattga ttcatgagga 1200 acattactgc taatctgctg ttaagtgaac ggtttttcat tttacccttt tgtttttcag 1260 tccaggttgg agatcgtagc tgctgctgct tgcacactag ggcacatgtg ggctttctct 1320 tgatctttgt gtcatttcag aattcaaaga ctgtgctacg ggagttctga acatggctgg 1380 gttcatgaag gcaaatgtat ggatgagagt gtggtttagg aaagagggca ctgatatcag 1440 attagaccta tgtgtttgca cccatctttg ttggcgatct gagtgcagtg tggcaagtgc 1500 acacctggca tccctgcgtc agatcgcgca ccttcaggtc gcgcaccttg cgctgaagga 1560 agatgacgca gagctttatc tgaaatcaga ggggagctat ccaaaatggg agtttggggg 1620 cagctaaagt tgacatgcga ataaattgat actgaaactt agcaacttct taaaagtgta 1680 aagaagcctc ataagatcat aaggaaaatg tatatatgct tttcacagct ttctagaatt 1740 ttttgacatt tgattttctt gagacttgta aacctggata tgttgaaggg tatttgttaa 1800 ttttactttt caaagatact ttaaaacagt agagctagca atgacacctt gcatttcatt 1860 tcaacactgc ttcaaggttt cttttgtata taattcttag aatgctcatt tcttttaaat 1920 ggtttaattt gtacagcaga ggaatgttat tgtagtagta tgtaactatt acctaatact 1980 gagtttttgc aaaaaacaat gaatgctcat atgtaattga aatacttcag atcacatgaa 2040 aatgctgatt taacatttaa gtatcacagc attaaaagaa aaagaaagta aaccagtcct 2100 ttgtattcag ttacctaatg gggtgccatc aataagctgc gatacagccc tggagctcag 2160 tcagccacac cttcctgcat cctattggcc ttattcattt taaatgagtt aatgaatctg 2220 ccagatctgt gaatgataga gattatgcta aattaatgct gattctttgt gtgtgtggga 2280 aatctctgta gagcaccttt tctttcttag actaagtaac ccagtacaat agttgtgaac 2340 tgaataatta aaactttggc ttctcttagg aaaagacgac ttcctagtca taggtgtcct 2400 atggggaaat ttattttttt ttaatgtcct gttccttaat gctgcaaatt atcagtattt 2460 ataaagtaac tgattttgca ccactttttt gttactgtga ccacggcaga acaatgtctt 2520 ctagactata tctatgtaaa gttattagaa tggtatctgt tcattttagt gatatgaaga 2580 tcacaactaa caactgacaa atcagagttt gccagttcaa attcagcatg gctgcagctg 2640 attaagaaat tgatatgatt attctttgct agcctctctt actaatggaa ttatatactg 2700 gccagtaaaa tgggcctccc aattgctgtt tcagcaggtt ttaaaccttc aggaacacca 2760 gttaggaaaa tagctccaga aaatatagat atattttatt tttattaaaa tggcagtcta 2820 catcataatt ggcatttctc aagactgtct ttaccagaat ctgtgtgaaa taaggcaatc 2880 tagtctcctt gaaaagaaaa tcccttggga tgtttaggaa ggaagacttg gccgtgatgt 2940 ggtgtcctgg ctttgtggtg tagtgctgtg tgtatggagt tagtgtaaaa acatggatta 3000 caccaagtgg aagaaacgtc ttcttgccaa gctcattctt agaacttaca catctagaac 3060 agcttccact ttggcagtga ggtcgtagcc tttcaggtgg aagaagtgag ggtgcagcgt 3120 gtcagacaca acattcatgt tactcttaca ttggaatctg aaggtagttc agacttcgtg 3180 ggtttgtttt taagcaaaac aatgtgaaaa catttaagtt tgaaatgttg catttgaagt 3240 tatgatcatt taatatatca tattaccaag actattatct g 3281

Claims (19)

What is claimed is:

1. An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of:
a) a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26, b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26, c) a polynucleotide sequence complementary to a), d) a polynucleotide sequence complementary to b), and e) an RNA equivalent of a) through d).

2. An isolated polynucleotide of claim 1, comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:1-26.

3. An isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide of claim 1.

4. A composition for the detection of expression of secretory polynucleotides comprising at least one of the polynucleotides of claim 1 and a detectable label.

5. A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 1, the method comprising:
a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof.

6. A method for detecting a target polynucleotide in a sample, said target polynucleotide comprising a sequence of a polynucleotide of claim 1, the method comprising:
a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof.

7. A method of claim 5, wherein the probe comprises at least 30 contiguous nucleotides.

8. A method of claim 5, wherein the probe comprises at least 60 contiguous nucleotides.

9. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of claim 1.

10. A cell transformed with a recombinant polynucleotide of claim 9.

11. A transgenic organism comprising a recombinant polynucleotide of claim 9.

12. A method for producing a secretory polypeptide, the method comprising:
a) culturing a cell under conditions suitable for expression of the secretory polypeptide, wherein said cell is transformed with a recombinant polynucleotide of claim 9, and b) recovering the secretory polypeptide so expressed.

13. A purified secretory polypeptide (SPTM) encoded by at least one of the polynucleotides of claim 2.

14. An isolated antibody which specifically binds to a secretory polypeptide of claim 13.

15. A method of identifying a test compound which specifically binds to the secretory polypeptide of claim 13, the method comprising the steps of:
a) providing a test compound;
b) combining the secretory polypeptide with the test compound for a sufficient time and under suitable conditions for binding; and c) detecting binding of the secretory polypeptide to the test compound, thereby identifying the test compound which specifically binds the secretory polypeptide.

16. A microarray wherein at least one element of the microarray is a polynucleotide of claim 3.

17. A method for generating a transcript image of a sample which contains polynucleotides, the method comprising the steps of:
a) labeling the polynucleotides of the sample, b) contacting the elements of the microarray of claim 16 with the labeled polynucleotides of the sample under conditions suitable for the formation of a hybridization complex, and c) quantifying the expression of the polynucleotides in the sample.

18. A method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence of claim 1, the method comprising:
a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide.

19. A method of claim 6 for toxicity testing of a compound, further comprising:
c) comparing the presence, absence or amount of said target polynucleotide in a first biological sample and a second biological sample, wherein said first biological sample has been contacted with said compound, and said second sample is a control, whereby a change in presence, absence or amount of said target polynucleotide in said first sample, as compared with said second sample, is indicative of toxic response to said compound.