DEFICIT OF HLA HOMOZYGOTES IN A CAUCASIAN ISOLATE

Deficits of HLA-A, -B homozygotes observed many years ago in two inbre d populations suggested negative selection against HLA homozygotes. To determine whether a similar deficiency would be observed in the S-leu t Hutterites, a well-characterized Caucasian isolate of European ances try, and to determine whether selection operated at the allele, locus, or haplotype level, observed and expected numbers of homozygotes were compared in 852 adult Hutterites. Deficits ranging from 11% to 24% we re observed for all five loci examined (HLA-A, -B, -C, -DR, and -DQ). However, these deficits were secondary to, and almost completely accou nted for by, a 64% loss of individuals homozygous for the haplotype. T here was no evidence of deficits affecting only a single allele or loc us. The data indicate strong negative selection against HLA homozygote s. This could be due, at least in part, to decreased fecundability amo ng couples sharing HLA-DR. However, these data suggest that additional selective factors acting at the level of the haplotype also operate i n this population.