Genetics of juvenile diabetes mellitus. A recessive gene closely linked to HLA D and with 50 per cent penetrance

Abstract

We investigated the genetic predisposition to juvenile diabetes in the families of 31 index cases in relation to the inheritance of the HLA system. The diabetes-predisposing gene was found to be recessive because the diabetic sibs in index cases shared both their HLA genes with a significantly increased frequency. Penetrance was estimated at 50 per cent because half the HLA-identical sibs in index cases were diabetic. These conclusions fit with published observations that the risk to sibs of patients is about 100 per cent, when both parents are normal. In three informative cases of recombination within HLA the predisposing gene traveled with the HLA D segment of the recombinant haplotype. We prepared tables for the computation of risks to relatives, based on the hypothesis of recessivity, HLA linkage and 50 per cent penetrance.