T cell regulatory genes associated with immune disease

• US 7,838,220 B2
• Filed: 09/15/2003
• Issued: 11/23/2010
• Est. Priority Date: 06/29/2001
• Status: Expired due to Fees

• Current Assignee: Dana-Farber Cancer Institute, Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Dana-Farber Cancer Institute, Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Freeman, Gordon, Dekruyff, Rosemarie, McIntire, Jennifer Jones, Umetsu, Dale T.
• Primary Examiner(s): BAUSCH, SARAE L
• Application Number:
  US10/663,497
• Publication Number:
  US 20050095593A1
• Time in Patent Office: 2,626 Days
• Field of Search: None
• US Class Current: 435/6.17
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

A genetic locus and corresponding family of proteins associated with regulation of immune development, function, and cell survival are provided. The locus comprising the TIM family is genetically associated with immune dysfunction, including atopy, autoimmunity, inflammatory bowel disease, dysplasia, and susceptibility to blood-bourne infectious diseases. Polymorphisms in the human TIM-1 gene and exposure to Hepatitis A Virus (HAV) are shown to be associated with protection from the development of atopy.

Claims

1. A method of screening for a human individual'"'"'s predisposition to atopy, the method comprising:

analyzing said individual for the presence of an INS157 polymorphism in TIM-1 by contacting a biological sample comprising DNA or mRNA from such individual with a probe that specifically binds to the nucleic acid sequence ATGACAACGACTGTTCCA, SEQ ID NO;

22, bases 472-489, encoding the amino acid sequence MTTTVP, SEQ ID NO;

25, residues 158-163;

detecting the presence of a complex formed between said probe and said genomic DNA, mRNA or a transcript thereof; and

analyzing said individual for the presence of hepatitis A virus (HAV) seropositivity wherein said seropositivity in an individual comprising an allele of TIM-1 comprising the amino acid sequence MTTTVP, SEQ ID NO;

25, residues 158-163 is indicative of a reduced risk of developing atopy.

2. A method of screening for a human individual'"'"'s predisposition to atopy, the method comprising:

analyzing said individual for the presence of an INS157 polymorphism in TIM-1 by contacting a biological sample comprising DNA or mRNA from said individual with a probe that specifically binds to a nucleic acid sequence encoding the amino acid sequence MTTTVP, SEQ ID NO;

25, residues 158-163;

wherein the presence of said INS157 polymorphism is indicative of an individual'"'"'s predisposition to develop said atopy.

3. The method according to claim 2, wherein said biological sample is blood or a derivative thereof.

4. The method according to claim 2, further comprising the step of:

analyzing said individual for the presence of hepatitis A virus (HAV) seropositivity,

wherein seropositivity in an individual expressing an allele of TIM-1 comprising the amino acid sequence MTTTVP, SEQ ID NO;

25, residues 158-163 is indicative of a reduced risk of developing atopy.