Linkage studies of HLA and insulin gene restriction fragment length polymorphisms in families with IDDM.

Linkage analysis of HLA DR antigen as well as DR and DQ restriction fragment length polymorphism (RFLP) data using the LIPED computer program and various three-allele disease locus models showed very close linkage to an insulin-dependent diabetes mellitus (IDDM)-susceptibility locus. RFLP data alone were equal or superior to conventional HLA antigen typing in the linkage analysis. Insulin gene restriction fragment data were analyzed for evidence of either a susceptibility locus linked to the insulin gene or an effect of alleles at the insulin locus on the HLA-linked susceptibility gene. No evidence was found of any effect of the insulin gene, and it is suggested that alternative explanations of the reported population associations between the insulin gene and IDDM should be considered.