Isolated polynucleotide associated with Type II diabetes mellitus and methods of use thereof

Abstract

The present invention provides isolated polynucleotides that include sequences from a region of human chromosome 20q between D20S119 and D20S195. The polynucleotides include polymorphisms associated with Type II diabetes and are useful as probes in screening for Type II diabetes. The invention further provides vectors and isolated host cells comprising the isolated polynucleotides. The invention further provides methods of detecting polymorphisms on chromosome 20q between D20S119 and D20S195, and methods of detecting a propensity to develop Type II diabetes, using the isolated polynucleotides of the invention.

What is claimed is:  
     
         1 . A method for detecting a propensity of an individual to develop Type II diabetes, comprising analyzing a polynucleotide sample derived from the individual for the presence of a polymorphism on chromosome 20q between D20S195 and D20S119, wherein said polymorphism is associated with Type II diabetes.  
     
     
         2 . The method of  claim 1 , wherein the polymorphism is a single nucleotide polymorphism.  
     
     
         3 . The method of  claim 2 , wherein the single nucleotide polymorphism is SNP58.  
     
     
         4 . The method of  claim 1 , wherein the analysis of the polynucleotide sample is performed by a method selected from the group consisting of detection of specific hybridization, measurement of allele size, restriction fragment length polymorphism analysis, allele-specific hybridization analysis, and sequencing of an amplified polynucleotide.  
     
     
         5 . The method of  claim 1 , wherein the presence of the polymorphism is determined by amplifying a segment of DNA within D20S195 and D20S119 that spans the polymorphism.  
     
     
         6 . The method of  claim 5 , further comprising the step of determining the size of the amplified segment.  
     
     
         7 . The method of  claim 5 , wherein a size of 214 base pairs of microsatellite marker D20S107 indicates that the individual has a propensity to develop Type II diabetes.  
     
     
         8 . A method of detecting a polymorphism associated with Type II diabetes in an individual, the method comprising: 
 a) contacting a polynucleotide sample derived from an individual with at least one probe for a sufficient amount of time to allow for specific hybridization of the sample polynucleotide to the probe under stringent hybridization conditions, wherein the probe comprises a sequence from a region between D20S195 and D20S119 that comprises SNP58; and    b) determining the presence of specific hybridization between the sample polynucleotide and the probe,    wherein specific hybridization of the probe to the sample polynucleotide provides for the detection of the SNP58 polymorphism in the individual.    
     
     
         9 . A method of confirming a phenotypic diagnosis of Type II diabetes in an individual, comprising analyzing a sample of a polynucleotide derived from an individual diagnosed as having Type II diabetes for the presence of a polymorphism on chromosome 20q between D20S195 and D20S119, wherein said DNA polymorphism is associated with Type II diabetes.  
     
     
         10 . The method of  claim 9 , wherein the polymorphism associated with Type II diabetes is SNP58.  
     
     
         11 . A pair of isolated nucleic acid molecules, each from about 10 to 200 nucleotides in length, the first nucleic acid molecule of the pair comprising a sequence of at least 10 contiguous nucleotides having 100% sequence identity to the nucleic acid sequence set forth in SEQ ID NO:7 and the second nucleic acid molecule of the pair comprising a sequence of at least 10 contiguous nucleotides having 100% sequence identity to the reverse complement of the nucleic acid sequence set forth in SEQ ID NO:7, wherein the sequence of the second nucleic acid molecule is located 3′ of the nucleic acid sequence of the first nucleic acid molecule in SEQ ID NO:7.  
     
     
         12 . The pair of  claim 11 , wherein the nucleic acid sequences of said first and second nucleic acid molecules are located 5′ and 3′, respectively, of the region of SEQ ID NO:7 corresponding to the location of SNP58.  
     
     
         13 . The pair according to  claim 11 , wherein said pair of nucleic acid molecules primes amplification of a portion of a human nucleic acid molecule comprising a nucleotide position corresponding to a mutation associated with Type II diabetes when used in a polymerase chain reaction with a human nucleic acid molecule as a template.  
     
     
         14 . An isolated polynucleotide comprising at least about 15 contiguous nucleotides of the sequence set forth in SEQ ID NO:7, wherein said polynucleotide comprises SNP58.  
     
     
         15 . A polynucleotide vector comprising the polynucleotide of  claim 14 .  
     
     
         16 . An isolated host cell comprising the polynucleotide of  claim 14 .  
     
     
         17 . An isolated host cell comprising the vector of  claim 15 .  
     
     
         18 . A kit comprising the pair of isolated nucleic acid molecules according to  claim 11 .  
     
     
         19 . The kit according to  claim 18 , further comprising: 
 a) a thermostable DNA polymerase;    b) deoxynucleotide triphosphates;    c) a buffer suitable for a polymerase chain reaction;    d) a solution comprising magnesium ions; and    e) instructions for use.