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WO1995005481A1 - Procede de diagnostic et therapie - Google Patents

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Publication number
WO1995005481A1
WO1995005481A1 PCT/GB1994/001801 GB9401801W WO9505481A1 WO 1995005481 A1 WO1995005481 A1 WO 1995005481A1 GB 9401801 W GB9401801 W GB 9401801W WO 9505481 A1 WO9505481 A1 WO 9505481A1
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WO
WIPO (PCT)
Prior art keywords
seq
atopy
sequence
ige
exon
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB1994/001801
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English (en)
Inventor
William Osmond Charles Michael Cookson
Julian Meurglyn Hopkin
Taro Shirakawa
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Oxford University Innovation Ltd
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Oxford University Innovation Ltd
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Filing date
Publication date
Priority claimed from GB939317185A external-priority patent/GB9317185D0/en
Priority claimed from GB9410669A external-priority patent/GB9410669D0/en
Application filed by Oxford University Innovation Ltd filed Critical Oxford University Innovation Ltd
Publication of WO1995005481A1 publication Critical patent/WO1995005481A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/16—Primer sets for multiplex assays
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/172—Haplotypes

Definitions

  • the invention relates to diagnosis of atopy or of a predisposition to atopy, and to treatment of atopic or potentially atopic individuals.
  • Atopy is a heterogeneous disorder
  • IgE immunoglobulin E
  • Fc ⁇ RI binds IgE to mucosal mast cells and plays a central role in allergy (1).
  • allergen binds to mast cell bound IgE
  • Fc ⁇ RI initiates a series of events leading to the cellular release of inflammatory
  • Atopy may be detected by positive skin prick tests of common allergens, by the presence of specific serum IgE against these allergens or by elevation of the total serum IgE. These three variables are strongly correlated with each other and with the presence of symptoms.
  • Atopy when defined as a prick skin test response to one or more common allergens, affects up to 50% of Western populations. As a result of atopy, as many as 10% of children suffer from asthma. Atopy results from complex interactions between heterogeneous genetic and environmental factors. The factors that govern the development of generalized atopic responsiveness, a characteristic of most atopies as they respond to many allergens, probably differ from those determining allergic response to any particular allergen or specific allergic symptoms.
  • CD20 is a proliferation and differentiation factor in B-lymphocyte lineage whose function is not known to be related to atopic IgE
  • the present invention provides a method of diagnosing atopy or a predisposition to atopy in an individual, which method comprises demonstrating the presence of a mutation or polymorphism in a specific
  • DNA sequence of a gene encoding the beta-subunit of the high affinity IgE receptor in the individual is provided.
  • the gene is on chromosome 11q. More particularly, the specific DNA sequence is located near the commencement of exon 6 of the gene on chromosome 11q.
  • the second variant, commencing at nucleotide 5640, is:
  • the specific DNA sequence may thus comprise one of the above sequences (i) and (ii), or a relevant portion thereof.
  • a relevant portion is a portion which is different to the wild type sequence.
  • the method may comprise amplification of the specific DNA sequence or a relevant portion thereof.
  • amplification technique which may be used is the amplification refractory mutation system (ARMS) PCR technique.
  • Another is PCR, which may be followed by probing of the amplification products with a
  • sequence-specific nucleic acid probe capable of
  • At least one primer is used which anneals to a DNA sequence comprising the mutant or variant sequence, but not to the wild type sequence.
  • sequences in exon 6 of the beta-subunit gene can be devised from the known DNA sequence, and in the case of ARMS, from the variant sequences (i) and (ii) above.
  • the method of diagnosis according to the invention may thus be performed on a DNA sample, but the invention is not limited to testing DNA.
  • the method may instead be performed on a product of the specific DNA sequence, such as messenger RNA (mRNA).
  • mRNA messenger RNA
  • the mutation or polymorphism may be identified in cDNA made from mRNA.
  • the method may involve
  • variant peptide or protein derived from the specific DNA sequence may be labelled and used for in vitro or in vivo diagnosis.
  • the variant peptide sequence can be synthesised by standard techniques eg. using an automatic synthesiser.
  • the antibodies can be made by administering the peptide in antigenic form to a suitable host.
  • Polyclonal or monoclonal antibodies may be prepared by standard techniques.
  • the invention provides peptides corresponding to variants of exon 6 of the gene encoding the high affinity IgE receptor on chromosome 11q, and
  • Such a peptide preferably comprises the amino acid sequence:
  • Glu Leu Val Leu Met SEQ ID NO: 3
  • Glu Leu Val Val Met SEQ ID NO: 5
  • a relevant portion is a portion which is different to the wild type.
  • the two above-mentioned amino acid sequences correspond to the variant nucleic acid sequences (i) and (ii).
  • the invention also provides antibodies to the variant peptides described above, and fragments of the antibodies, the antibodies or fragments will be useful in the method of diagnosis according to the invention, to identify protein variants.
  • the invention provides, as new chemical compounds, nucleic acids comprising the sequence (i) or (ii) above or complementary DNA or RNA.
  • the invention provides a nucleic acid comprising a first portion which corresponds substantially to the whole or part of exon 6 of the gene encoding the beta-subunit of the high-affinity receptor for IgE, which first portion includes one of the following sequences:
  • Probes comprising a wild type or variant oligonucleotide or a nucleic acid as described herein, linked to a signal moiety or immobilised on a surface, are also considered to be part of the invention.
  • Variant probes will be useful for identifying variant phenotypes and wild type probes can be used for control purposes.
  • the invention therefore provides diagnostic tests for functional polymorphisms within and close to the beta chain gene. These tests may be used for postnatal diagnosis of an atopic predisposition, in order to carry out preventative measures against allergen sensitisation in early childhood. The tests may also identify asthmatic or other atopic subjects who respond to particular treatment modalities. The tests may also identify individuals susceptible to industrial asthma, or to the effects of cigarette smoke and other
  • Treatments may be developed for example by testing pharmacologic compounds against cell systems (eg. monkey cos cells) containing the receptor genes. Effects of pharmacologic compounds can be tested on wild type and variant-encoded receptors, to look for compounds which eg. down-regulate the variant receptor but not the wild type receptor. High throughput screening assays will be possible. In other words, the mutant beta chain would be part of an assay to develop new drugs, or proteins to alter the receptor function . A strategy based on "antisense RNA" to block the action of the beta chain can also be envisaged.
  • Example 2 In each of 10 atopic families in which Leu181 was found, transmission was through the mother and a strong association between the variant and atopy was demonstrable in the children.
  • Fc ⁇ RI is comprised of three subunits ⁇ , ⁇ and gamma 2 ; in human, ⁇ and gamma are encoded on chromosome 1 and the ⁇ subunit on chromosome 11 (5).
  • Fc ⁇ RI is expressed on mast cells, basophils, monocytes and Langerhans cells. The receptor plays a central role in the mediation of IgE dependent allergic
  • Fc ⁇ RI causes release from the mast cell of cytokines, including IL-4, which are implicated in the up-regulation of mast cell and helper T-cell subtype 2 (TH2) development and of IgE production by B-lymphocytes.
  • Lung mast cells that express cell contact signals including CD40 ligand may, in the presence of IL-4, regulate local B lymphocyte IgE production independently of T lymphocytes.
  • Variants of Fc ⁇ RI- ⁇ might promote the atopic state either by enhanced release of pro-inflammatory mediators by mast cells (to cause more symptomatic disease) or by enhanced mast cell expression of IL-4 and CD40 ligand (to cause more local B lymphocyte IgE production).
  • Leu181 /Leu183 should be considered to be a polymorphism or variant of normal, rather than a mutation.
  • Leul 81 /Leul 83 was found exclusively in the Australian population, although Leul 81 seems much more common in English subjects (Examples 1 and 2). This indicates possible variation between populations.
  • Figure 1 is a schematic model of the ⁇ -subunit of Fc ⁇ RI (3) demonstrating four transmembrane domains and the position of the leucine substitutions (181 and 183 as solid symbols) within the 4th
  • Figure 2 shows results of ARMS testing for Leu181 in 60 nuclear families identified through an asthmatic proband. The 10 families with the variant are shown. No family was found with Leu183 variant.
  • Atopy was defined as described (30,31), by the presence of a total serum IgE elevated above normal values (Phazedym PRIST, Pharmacia), or a positive skin prick test to house dust mite or grass pollen allergens (Dome-Hollister-Stier, Spokane, USA) > 2mm > a negative control, or a positive specific IgE titre > 0.35 KU A L -1 for the same allergens (Pharmacia CAP system).
  • the reaction mixture contained 1 ⁇ g of genomic DNA in a buffer (MgCl 2 1.5mmol L -1 Tris 100 mmol L -1 , KC1 500 mmol L -1 , gelatin 1mg ml -1 ), with 200 ⁇ M of dNTPs, 0.5 ⁇ l Taq polymerase, and 10% DMSO made up to a final volume of 100 ⁇ L.
  • a buffer MgCl 2 1.5mmol L -1 Tris 100 mmol L -1 , KC1 500 mmol L -1 , gelatin 1mg ml -1
  • reaction 1 The primers for exons 1 to 3 (reaction 1) were: 5'-TGG GGA CAA TTC CAG AAG AAG-3' and 5' - CCG GAA TTC AGG TTT CTC ATG GGA TAA - 3'; and for exons 4 to 6 (reaction 2) were : 5'-TTA GGT GTC TCT CAA CCC ATC-3' and 5'-CCG GAA TTC CTC ACA AGC CTT CTG TAC-3'; and for exon 7 (reaction 3) were: 5'-CAG CTA ACT TAG GAG GCT GAG-3 ' and 5'-TAT CAG GCG AAT AAA TCT AAT GTA-3'. 25 cycles of PCR were carried out for each reaction. The products were then cut with restriction enzymes: reaction 1 used BamHI, PstI and EcoRI to give two major fragments of 0.7 and 1.7kb.
  • reaction 2 was digested with Smal and EcoRI to yield one major fragment of 2.4 kb; reaction 3 was digested with SmaI and BamHI to give a single major fragment of 0.7 kb.
  • the four fragments were cloned into M13 by standard methods. After checking inserts with a forward universal primer, singla-strand sequencing was carried out by the dideoxy chain
  • Atopy phenotype testing was carried out as described in Example 1. In the random patient sample, total and allergen-specific serum IgE's were assayed but skin prick test and clinical data were not
  • the Arms method applied was modified from ref.(18).
  • the primers to give a 237 bp band were: a universal upstream primer 5'-AAG TTA TCT ACT GCA AGT GAC GAT CTC T-3' (SEQ ID NO: 8) together with downstream primers to detect: wild type sequence (Ile181, Val183), 5'-GGT GAG AAA CAG CAT CAT CAC TAC AAT-3' (SEQ ID NO: 9); the Leu181 variant, 5 '-GGT GAG AAA CAG CAT CAT CAA TAC CAA-3' (SEQ ID NO: 10); the
  • PCR was performed in a Perkin Elmer Cetus DNA thermal cycler using a preliminary cycle (94'C denaturation for 5 min, 60oC annealing for 2 min, and 72 "C extension for 2 min) and then 34 cycles (94oC for 2 min, 60'C for 2 min, and 72°C for 2 min). Amplification products underwent electrophoresis in 4% agarose gels before ethidium staining and scoring by two independent observers.
  • Genotyping and phenotyping were carried out randomised and double blind. The atopy phenotype was ascribed prior to DNA analysis. Freshly extracted DNA samples from all subjects were coded in random order, obscuring all family links. The ARMS testing was performed in duplicate with positive and negative controls. The presence of Leu181 was tested and confirmed by DNA sequencing in the 10 families,
  • the study population consisted of 1004 subjects in 232 nuclear families from the rural coastal town of Busselton, 200 miles from the main population centre of Perth in South-Western Australia. Families were identified through adults aged 55 or under, from an electoral roll of approximately 9,000. It was emphasised that people who considered themselves normal were important to the study. However, there is known to be a high prevalence of atopy in Bussleton and other Western Australian populations.
  • the total serum IgE and specific IgE to whole Dermatophagoides pteronyssinus and Phleum pratense was determined (Pharmacia CAP system FEIA, Sweden).
  • a specific IgE RAST class 1 (> 0.35 KU/L) was considered positive.
  • Eosinophil and white cell numbers were estimated by automatic counter (Western Diagnostic Laboratories, Western Australia).
  • DNA was obtained from peripheral blood leucocytes by phenol/chloroform extraction. Fc €RI- ⁇
  • Leul 81 detection was carried out by the Amplification
  • Genomic DNA samples (0.25-0.30 ⁇ g) were amplified in a total volume of 50 ⁇ l containing 0.5 ⁇ M of oligonucleotide primers 5FU, 3FU and 5WK, 0.1 ⁇ M of 3M,
  • reaction mixture 40 ⁇ l without enzyme was heated to 95oC for 5 min using a thermal cycler (Hybaid) and held at 80°C for the addition of enzyme (2 units of enzyme in 10 ⁇ l of reaction buffer). Reaction conditions then followed 35 cycles of 94oC for 1 min, 60oC for 2 min, 72°C for 2 min and 1 cycle 72°C for 10 min.
  • a member of each family segregating Leul 81 was sequenced by the Sanger method to ensure accuracy of the PCR reaction, and to determine if Leul 83 was present.
  • Genotyping was carried out without knowledge of phenotype and vice versa.
  • the assay for Leul 81 failed to amplify in 5 individuals (0.5%). Of the remaining 999 subjects, 45 (4.5%) were positive for Leul 81. Twenty-one of these were children; 8 (in 7 sibships) had inherited the variant paternally, and 13 (in 7 sibships) maternally. Sequencing of an individual from each family showed that in each case Leu181 was accompanied by Leul 83, so that only the Leul 81 /Leul 83 polymorphism was found in this population.
  • Leul 81 /Leul 83 maternally were all atopic (Table 3a). Eleven had symptoms of wheeze or rhinitis or both, and a twelfth, who denied symptoms, had previous physician-diagnosed and treated asthma. Compared to the 531 other children in the population, the 13 had
  • Leul 81 /Leul 83 paternally were, by contrast, non-atopic, with negative skin tests and RASTs (Table 3b). Their skin tests, RASTs and eosinophil counts were
  • Phenotype Leu181 Fisher's p Odds ratio (95%
  • Fig.2 The phenotype of families are shown in Fig.2. Individuals are numbered from left to right, beginning with the parents.
  • Hopkin,J.M Linkage between immunoglobulin E responses underlying asthma and rhinitis and chromosome 11 q . Lancet i, 1292-1295(1989)
  • hyperresponsiveness exclusion of linkage to markers on chromosomes 11 and 6p. Clin. Exp.
  • a frequent human CD20 (B1) differentiation antigen DNA polymorphism detected with Mspi is located near 11 q12- 13. Nucl. Acids Res. 18, 207(1990).
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • FEATURE FEATURE
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • xi SEQUENCE DESCRIPTION: SEQ ID NO: 7:
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)
  • MOLECULE TYPE DNA (genomic)

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Abstract

L'invention concerne un procédé de diagnostic de l'atopie ou d'une prédisposition à l'atopie chez un individu, et qui consiste à mettre en évidence la présence d'une mutation ou d'un polymorphisme dans une séquence d'ADN spécifique d'un gène codant la sous-unité bêta du récepteur de haute affinité de l'IgE chez l'individu. Deux variantes de séquences d'ADN liées à l'atopie sont établies comme suit: 5' GAA TTG GTA TTG ATG (numéro d'identification de séquence: 2), 5' GAA TTG GTA GTG ATG (numéro d'identification de séquence: 4), les deux commençant au niveau du nucléotide 5640 du gène de la sous-unité bêta. Pour la première fois, l'invention donne la possibilité d'identifier des individus risquant génétiquement de développer une maladie atopique.
PCT/GB1994/001801 1993-08-18 1994-08-17 Procede de diagnostic et therapie Ceased WO1995005481A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB9317185.8 1993-08-18
GB939317185A GB9317185D0 (en) 1993-08-18 1993-08-18 Diagnostic method and therapy
GB9410669.7 1994-05-27
GB9410669A GB9410669D0 (en) 1994-05-27 1994-05-27 Diagnostic method and therapy

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WO1995005481A1 true WO1995005481A1 (fr) 1995-02-23

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PCT/GB1994/001801 Ceased WO1995005481A1 (fr) 1993-08-18 1994-08-17 Procede de diagnostic et therapie

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997008338A1 (fr) * 1995-08-29 1997-03-06 Isis Innovation Limited Atopie: diagnostic et therapie
US5705615A (en) * 1994-10-06 1998-01-06 Beth Israel Deaconess Medical Center Antibodies specific for HTm4
WO1998001580A1 (fr) * 1996-07-10 1998-01-15 Beth Israel Deaconess Medical Center GENE RECOMBINANT HTm4, PROTEINE ET UTILISATION DANS DES PROCEDES DE DETECTION D'ATOPIE HEREDITAIRE
WO1999032659A1 (fr) * 1997-12-22 1999-07-01 Stiftelsen Universitetsforskning Bergen (Unifob) Methode pour le pronostic de maladie, par l'etablissement du genotype du recepteur fc
WO1999050449A1 (fr) * 1998-03-27 1999-10-07 Isis Innovation Limited Polymorphisme ii: liaison de l'asthme avec un locus du chromosome 4
WO1999050450A1 (fr) * 1998-03-27 1999-10-07 Isis Innovation Limited Polymorphisme iii: liaison de l'atopie avec un locus du chromosome 13
WO2001014588A1 (fr) * 1999-08-24 2001-03-01 Genaissance Pharmaceuticals, Inc. Isogenes cibles de medicament: polymorphismes dans le gene de la chaine beta du recepteur e d'immunoglobuline
WO2001021816A1 (fr) * 1999-09-21 2001-03-29 Isis Innovation Limited Procede de modulation de l'expression de la surface d'une cellule receptrice de l'immunoglobine e
WO2001057087A3 (fr) * 2000-02-02 2002-02-07 Curagen Corp Nouvelle proteine du type sous-unite beta de recepteur de haute affinite pour l'immunoglobuline epsilon (fceb) et acides nucleiques codant pour celle-ci
WO2002086113A3 (fr) * 2001-04-24 2003-11-27 Isis Innovation Enzyme et marqueur snp pour le depistage d'une maladie

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
COOKSON, W. ET AL: "Maternal inheritance of atopic IgE responsiveness on chromosome 11q", THE LANCET, vol. 340, 15 August 1992 (1992-08-15), UK., pages 381 - 84 *
EMBL Database entry CEZC84 Accession Number Z19157; 27 December 1992 Sulston, J. et al: C. Elegans Sequencing & Nature 356:37-41, 1992 *
Geneseq Database entry R14770 Accession number R14770; 3 February 1992 Descriptor Field: Beta subunit of high affinity IgE receptor *
GOLDSTEIN, B. ET AL: "The rat insulin receptor", MOLULAR ENDOCRINOLOGY, vol. 4, no. 2, 1990, BALTIMORE US, pages 235 - 244 *
HOVE-JENSEN, B. ET AL: "Phosphoribosylphosphate synthetase of Escherichia coli", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 8, 25 May 1986 (1986-05-25), BALTIMORE US, pages 6765 - 71 *
KÜSTER, H. ET AL: "The gene and cDNA for the human high affinity immunoglobulin E receptor beta-chain and Expression of the complete human receptor.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 267, no. 18, 25 June 1992 (1992-06-25), US, pages 12782 - 87 *
SANDFORD, A. ET AL: "Localisation of atopy and beta-subunit of high-affinity IgE receptor (Fc eta-RI) on chromosome 11q.", THE LANCET, vol. 341, 6 February 1993 (1993-02-06), UK, pages 332 - 34 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5972688A (en) * 1994-10-06 1999-10-26 Beth Israel Deaconess Medical Center HTm4 methods of treatment and assays, agonists and antagonists
US5705615A (en) * 1994-10-06 1998-01-06 Beth Israel Deaconess Medical Center Antibodies specific for HTm4
WO1997008338A1 (fr) * 1995-08-29 1997-03-06 Isis Innovation Limited Atopie: diagnostic et therapie
US6114151A (en) * 1995-08-29 2000-09-05 Isis Innovation Limited Detection of a variant form of high affinity receptor to IgE FCεRIβ using primers and probes
WO1998001580A1 (fr) * 1996-07-10 1998-01-15 Beth Israel Deaconess Medical Center GENE RECOMBINANT HTm4, PROTEINE ET UTILISATION DANS DES PROCEDES DE DETECTION D'ATOPIE HEREDITAIRE
WO1999032659A1 (fr) * 1997-12-22 1999-07-01 Stiftelsen Universitetsforskning Bergen (Unifob) Methode pour le pronostic de maladie, par l'etablissement du genotype du recepteur fc
AU764006B2 (en) * 1997-12-22 2003-08-07 Stiftelsen Universitetsforskning Bergen (Unifob) Method for disease prognosis based on Fc receptor genotyping
WO1999050450A1 (fr) * 1998-03-27 1999-10-07 Isis Innovation Limited Polymorphisme iii: liaison de l'atopie avec un locus du chromosome 13
WO1999050449A1 (fr) * 1998-03-27 1999-10-07 Isis Innovation Limited Polymorphisme ii: liaison de l'asthme avec un locus du chromosome 4
WO2001014588A1 (fr) * 1999-08-24 2001-03-01 Genaissance Pharmaceuticals, Inc. Isogenes cibles de medicament: polymorphismes dans le gene de la chaine beta du recepteur e d'immunoglobuline
WO2001021816A1 (fr) * 1999-09-21 2001-03-29 Isis Innovation Limited Procede de modulation de l'expression de la surface d'une cellule receptrice de l'immunoglobine e
WO2001057087A3 (fr) * 2000-02-02 2002-02-07 Curagen Corp Nouvelle proteine du type sous-unite beta de recepteur de haute affinite pour l'immunoglobuline epsilon (fceb) et acides nucleiques codant pour celle-ci
WO2002086113A3 (fr) * 2001-04-24 2003-11-27 Isis Innovation Enzyme et marqueur snp pour le depistage d'une maladie

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