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INSULIN-dependent (type I) diabetes mellitus (IDDM) follows an autoimmune destruction of the insulin-producing beta-cells of the pancreas. Family and population studies indicate that predisposition is probably polygenic. At least one susceptibility gene lies within the major histocompatibility complex and is closely linked to the genes encoding the class II antigens, HLA-DR and HLA-DQ (refs 3, 4). Fine mapping of susceptibility genes by linkage analysis in families is not feasible because of infrequent recombination (linkage disequilibrium) between the DR and DQ genes. Recombination events in the past, however, have occurred and generated distinct DR-DQ haplotypes, whose frequencies vary between races. DNA sequencing and oligonucleotide dot-blot analysis of class II genes from two race-specific haplotypes indicate that susceptibility to IDDM is closely linked to the DQA1 locus and suggest that both the DQB1 (ref. 7) and DQA1 genes contribute to disease predisposition.

Original publication

DOI

10.1038/338587a0

Type

Journal article

Journal

Nature

Publication Date

13/04/1989

Volume

338

Pages

587 - 589

Keywords

Chromosome Mapping, Continental Population Groups, Diabetes Mellitus, Type 1, Genes, MHC Class II, Genetic Predisposition to Disease, HLA-DQ Antigens, HLA-DR Antigens, Humans