Evidence for the presence of insulin-dependent diabetes-associated alleles on the distal part of mouse chromosome 6

Abstract

Type 1 diabetes (IDDM) is a complex disorder with multifactorial and polygenic etiolopy. A genome-wide screen performed in a BCl cohort of a cross between the nonobese diabetic (NOD) mouse with the diabetes-resistant feral strain PWK detected a major locus contributing to diabetes development on the distal part of chromosome 6. Unlike the majority of other Idd loci identified in intraspecific crosses, susceptibility is associated with the presence of the PWK allele. Genetic linkage analysis of congenic lines segregating PWK chromosome 6 segments in a NOD background confirmed the presence of the Idd locus within this region. The genetic interval defined by analysis of congenic animals showed a peak of significant linkage (P = 0.0005) centered on an ~ 9-cM region lying between D6Mit11 and D6Mit25 genetic markers within distal mouse chromosome 6.