Genetic Components Involved in Disease

Initial study of the HLA component to type-1 diabetes gave results compatible with a simple recessive model (with incomplete penetrance) (22,97). Only later did the extensive heterogeneity of the HLA component to type-1 diabetes emerge. Genetic heterogeneity was definitively established by the demonstration that the HLA class II DR3 and DR4 serological 

The original application of the haplotype method was to allele frequency data (99). Direct roles of only HLA DR3 and DR4 serological types in type-1 diabetes were excluded, since HLA B locus variation on these haplotypes was different in patients and controls. At the amino acid level, a combination of sites at DRB1, DQA1, and DQB1 was shown to be highly correlated with the DR-DQ contribution to type-1 diabetes and to correlate with disease incidence (101). 

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