HLA and disease: predictions for HLA haplotype sharing in families

An analysis of published data on the segregation of HLA haplotypes in families with more than one individual affected with insulin-dependent diabetes mellitus or multiple sclerosis yields three conclusions: (1) In families with unaffected parents, affected sib pairs are much more often HLA haplotype identical in sibships with two affected sibs than in sibships with three or four affected sibs (P less than .01). (2) In families with unaffected parents and HLA half-identical affected sibs, well siblings more often receive the single haplotype not found in the affected sibs than is expected by chance (P less than .05). (3) In families with one affected parent, well siblings of affected individuals may share with the affected child a haplotype from the unaffected parent less than 50% of the time (P less than .10). These results are consistent with the premise that in some non-Mendelian, familial, HLA-associated disease more than one gene may contribute to susceptibility to the disorder.