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The diabetes-prone BioBreeding (BB) and Komeda diabetes-prone (KDP) rats are both spontaneous animal models of human autoimmune, T-cell-associated type 1 diabetes. Both resemble the human disease, and consequently, susceptibility genes for diabetes found in these two strains can be considered as potential candidate genes in humans. Recently, a frameshift deletion in Ian4, a member of the immune-associated nucleotide (Ian)-related gene family, has been shown to map to BB rat Iddm1. In the KDP rat, a nonsense mutation in the T-cell regulatory gene, Cblb, has been described as a major susceptibility locus. Following a strategy of examining the human orthologues of susceptibility genes identified in animal models for association with type 1 diabetes, we identified single nucleotide polymorphisms (SNPs) from each gene by resequencing PCR product from at least 32 type 1 diabetic patients. Haplotype tag SNPs (htSNPs) were selected and genotyped in 754 affected sib-pair families from the U.K. and U.S. Evaluation of disease association by a multilocus transmission/disequilibrium test (TDT) gave a P value of 0.484 for IAN4L1 and 0.692 for CBLB, suggesting that neither gene influences susceptibility to common alleles of human type 1 diabetes in these populations.

Type

Journal article

Journal

Diabetes

Publication Date

02/2004

Volume

53

Pages

505 - 509

Keywords

Adaptor Proteins, Signal Transducing, Animals, Codon, Nonsense, Diabetes Mellitus, Type 1, Family, Frameshift Mutation, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-cbl, Rats, Rats, Inbred BB, Siblings, Species Specificity, Ubiquitin-Protein Ligases