Human single nucleotide polymorphisms in ion channels and other proteins

Abstract

The invention provides polynucleotide fragments corresponding to the genomic and/or coding regions of these genes which comprise at least one polymorphic site per fragment. Allele-specific primers and probes that hybridize to these regions, and/or that comprise at least one polymorphic site are also provided. The polynucleotides, primers, and probes of the present invention are useful in phenotype correlations, paternity testing, medicine, and genetic analysis. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders, particularly cardiovascular diseases related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

1 - 14 . (canceled) 
     
     
         15 . A method of diagnosing the presence of diabetes in a human subject, or likelihood of a human subject acquiring diabetes, the method comprising:
 (a) obtaining an LSI-1 DNA sequence from the subject to be diagnosed; and   (b) analyzing the LSI-1 sequence from said subject to determine a nucleotide present at a polymorphic nucleotide position, wherein said polymorphic nucleotide position is located in the 5′ untranslated region (UTR) of LSI-1 and is flanked on its 5′ end by a nucleotide sequence comprising SEQ ID NO:61 and is flanked on its 3′ end by a nucleotide sequence comprising SEQ ID NO:62, and wherein the presence of a G at said polymorphic nucleotide position indicates that the subject has or is more likely to acquire diabetes than subjects having a T, thereby diagnosing the presence of diabetes, or likelihood of the subject acquiring diabetes.   
     
     
         16 . The method of  claim 15 , wherein the determining comprises sequencing the LSI-1 DNA sequence. 
     
     
         17 . The method of  claim 16 , wherein the sequencing is performed with a forward primer comprising a nucleotide sequence of SEQ ID NO:117 or a reverse primer comprising a nucleotide sequence of SEQ ID NO:118. 
     
     
         18 . The method of  claim 15 , wherein the determining comprises the step of amplifying the LSI-1 DNA sequence. 
     
     
         19 . The method of  claim 18 , further comprising the step of subjecting a product(s) of the amplifying to a genetic bit analysis (GBA) reaction. 
     
     
         20 . The method of  claim 18 , wherein the amplifying comprises the step of amplifying LSI-1 DNA sequence by polymerase chain reaction (PCR). 
     
     
         21 . The method of  claim 20 , wherein the PCR is performed with a forward primer comprising a nucleotide sequence of SEQ ID NO:117 and a reverse primer comprising a nucleotide sequence of SEQ ID NO:118. 
     
     
         22 . A method for determining whether a human subject has an increased likelihood of having or developing diabetes wherein the method comprises:
 (a) obtaining a LSI-1 DNA nucleic acid sample from the subject;   (b) analyzing LSI-1 nucleic acids present in the nucleic acid sample to determine a nucleotide present at a nucleotide position which is flanked on its 5′ end by a nucleotide sequence comprising SEQ ID NO:61 and is flanked on its 3′ end by a nucleotide sequence comprising SEQ ID NO:62; and   (c) determining that the subject has an increased likelihood of having or developing diabetes if the subject is homozygous or heterozygous for a G at nucleotide position which is flanked on its 5′ end by a nucleotide sequence comprising SEQ ID NO:61 and is flanked on its 3′ end by a nucleotide sequence comprising SEQ ID NO:62 as compared to subjects having a T at nucleotide position which is flanked on its 5′ end by a nucleotide sequence comprising SEQ ID NO:61 and is flanked on its 3′ end by a nucleotide sequence comprising SEQ ID NO:62.