HLA haplotype segregation in families of type 1 diabetics.
The hypothesis of linkage between HLA and a disease susceptibility (DS) locus (or loci) for type 1 diabetes was tested. HLA segregation was random among 57 non-diabetic sibs but not among 39 diabetic sibs, suggesting that susceptibility to type 1 diabetes may be due to an HLA-linked gene(s). The data did not fit a genetic model involving either a single recessive or dominant gene. The excess of HLA-identical diabetic sibs and the reduced number who were HLA-discordant compared to expected numbers indicated that factors from both paternal and maternal haplotypes were necessary for DS. In 1 of the 3 families with a diabetic parent and more than one diabetic sib, the diabetic sibs inherited different haplotypes from the affected parent, suggesting that either of these haplotypes conferred DS. HLAB 8, B 18 and B 40 were increased in frequency among 97 unrelated type 1 diabetics compared with 238 controls, especially among those with onset age less than 10 years. This early onset group may represent a subtype of type 1 diabetes.
D000293:Adolescent; D000328:Adult; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; D059947:HLA-B40 Antigen; D015795:HLA-B8 Antigen; D006801:Humans; D008957:Models, Genetic
D006680:HLA Antigens; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; D059947:HLA-B40 Antigen; D015795:HLA-B8 Antigen