Genetic Alterations on Chromosomes 21q, 6q and 15q and Methods of Use Thereof for the Diagnosis and Treatment of Type I Diabetes

A method for determining the presence or absence of at least one specific nucleotide in a target nucleic acid for the diagnosis of T1D, said method comprising the steps of:

• a) providing a detectable amount of a target nucleic acid polymer isolated from a chromosomal region known to be associated with diabetes,
• b) hybridizing said detectable amount of the nucleic acid polymer with one or more oligonucleotide primers, wherein each primer has a nucleotide sequence that is complementary to a sequence in the target nucleic acid polymer,
• c) exposing the hybridized nucleic acid polymer to a polymerization agent in a mixture containing at least one deoxynucleotide, said deoxynucleotide comprising a detectable label,
• d) analyzing the polymerization mixture of step (c) for the presence or absence of the primer extension product containing the labeled deoxynucleotide, whereby the identity of the specific nucleotide at the defined site is determined;
• and
• e) assessing said target nucleic acid for the presence of a genetic alteration at said at least one single nucleotide loci, the presence of the polymorphism being associated with an altered risk of developing T1D.

A method for identifying agents which modulate beta cell destruction leading to T1D comprising:

• a) providing a test subject having cells expressing a SNP selected from the group consisting those set forth in Tables 1, 2 , 4 or 5;
• b) providing a test subject having cells which express the cognate sequence lacking the SNPs of step a);
• c) contacting the cells of steps a) and b) with an agent;
• and
• d) determining whether said agent alters beta cell destruction of the cells of step a) relative to those of step b), thereby identifying agents which modulate autoimmune beta cell destruction.

A method for identifying agents which modulate the diabetic phenotype:

• a) providing cells expressing a single nucleotide polymorphism selected from the group consisting of those set forth in Table 1, 2, 4 and 5;
• b) providing cells which express the cognate sequences which lack the polymorphisms of step a);
• c) contacting the cells of steps a) and b) with a test agent and
• d) analyzing whether said agent alters an diabetic associated parameter in cells contacted in step a) relative to those of step b), thereby identifying agents which modulate the diabetic phenotype.