TCF-1 nucleotide sequence variation

Abstract

Methods and reagents for determining sequence variants present at the TCF-1 locus, which facilitates identifying individuals at risk for Th1 diseases, such as type 1 diabetes or multiple sclerosis, or Th2 diseases, such as allergic asthma or atopy.

We claim:  
     
         1 . A method for characterizing an individual as possessing a factor contributing to an increased tendency for responding to an antigen with a Th1 or Th2 response; wherein said method comprises: 
 (a) determining the genotype of said individual with respect to the nucleotide present at position 883 of the TCF-1 gene, wherein said gene sequence is provided as SEQ ID NO: 1;    (b) classifying said patient based on the result obtained from step (a), wherein the presence of an a allele indicates a factor contributing to an increased tendency for responding to an antigen with a Th1 response, and the presence of a C allele indicates a factor contributing to an increased tendency for responding to an antigen with a Th2 response.    
     
     
         2 . A method for characterizing an individual as possessing a factor contributing to an increased risk of a Th1-mediated disease or an increased risk of a Th2-mediated disease, wherein said method comprises: 
 (a) determining the genotype of said individual with respect to the nucleotide present at position 883 of the TCF-1 gene, wherein said gene sequence is provided as SEQ ID NO: 1;    (b) classifying said patient based on the result obtained from step (a), wherein the presence of an A allele indicates a factor contributing to an increased risk of a Th1-mediated disease, and the presence of a C allele indicates a factor contributing an increased risk of a Th2-mediated disease.    
     
     
         3 . A method for characterizing an individual as possessing a factor contributing to an increased risk of a Th1-mediated disease, wherein said method comprises: 
 (a) determining the genotype of said individual with respect to the nucleotide present at position 883 of the TCF-1 gene, wherein said gene sequence is provided as SEQ ID NO: 1;    (b) classifying said patient based on the result obtained from step (a), wherein the presence of an A allele indicates a factor contributing to an increased risk of a Th 1-mediated disease.    
     
     
         4 . A method of  claim 3 , wherein said Th1-mediated disease is type 1 diabetes or multiple sclerosis.  
     
     
         5 . A method for characterizing an individual as possessing a factor contributing to an increased risk of a Th2-mediated disease, wherein said method comprises: 
 (a) determining the genotype of said individual with respect to the nucleotide present at position 883 of the TCF-1 gene, wherein said gene sequence is provided as SEQ ID NO: 1;    (b) classifying said patient based on the result obtained from step (a), wherein the presence of a C allele indicates a factor contributing to an increased risk of a Th2-mediated disease.    
     
     
         6 . A method of  claim 5 , wherein said Th2-mediated disease is allergic asthma or atopy.  
     
     
         7 . A method for determining the genotype of a sample with respect to the nucleotide present in the TCF-1 gene at position 883, comprising: 
 (a) contacting nucleic acid from said sample with an oligonucleotide probe exactly complementary to an allele that is an A allele or a C allele in a region encompassing position 883 under conditions such that hybridization occurs if and only if said allele is present; and    (b) detecting if hybridization occurs, which indicates the presence of said allele.    
     
     
         8 . A method of  claim 7 , wherein a segment of region of said nucleic acid encompassing said region is amplified prior to, or concurrent with step (a).  
     
     
         9 . A method of  claim 8 , wherein said probe is selected from the group consisting of KW196 (SEQ ID NO: 8) or KW118 (SEQ ID NO: 9).  
     
     
         10 . A method for determining the genotype of a sample with respect to the nucleotide present in the TCF-1 gene at position 883, comprising: 
 (a) contacting nucleic acid from said sample with a set of oligonucleotide primers comprising an allele-specific primer specific for an allele that is an A allele or a C allele under amplification conditions such that amplification occurs using said allele-specific primer if and only if said allele is present; and    (b) detecting if amplification occurs, which indicates the presence of said allele.    
     
     
         11 . A method of  claim 10 , wherein said allele specific primer is GZ351B (SEQ ID NO: 4) or GZ374B (SEQ ID NO: 5).  
     
     
         12 . An isolated oligonucleotide, wherein said oligonucleotide is exactly or substantially complementary to either strand of SEQ ID NO: 1 in a region which encompasses the polymorphic site at nucleotide position 883, and wherein said oligonucleotide is exactly complementary to SEQ ID NO: 1 at said nucleotide position 883.  
     
     
         13 . An isolated oligonucleotide of  claim 12 , wherein said region is about 10 to about 35 nucleotides in length.  
     
     
         14 . An isolated oligonucleotide of  claim 13  selected from the group consisting of GZ351B (SEQ ID NO: 4), GZ374B (SEQ ID NO: 5), KW196 (SEQ ID NO: 8), KW118 (SEQ ID NO: 9), and the exact complements thereof.  
     
     
         15 . A kit for determining the genotype of an individual TCF-1 genotype with respect to the nucleotide present in the TCF-1 gene at position 883 locus comprising an oligonucleotide of  claim 12 .  
     
     
         16 . A kit for determining the genotype of an individual TCF-1 genotype with respect to the nucleotide present in the TCF-1 gene at position 883 locus comprising an oligonucleotide of  claim 13 .  
     
     
         17 . A kit for determining the genotype of an individual TCF-1 genotype with respect to the nucleotide present in the TCF-1 gene at position 883 locus comprising an oligonucleotide of  claim 14.