Extended major histocompatibility complex haplotypes in man: Role of alleles analogous to murine t mutants

Abstract

Extended haplotypes involving HLA-A,B,D,DR, the complotypes, and glyoxalase I appear to occur at appreciable frequency in man and differ from population to population. We here suggest that, in addition to previously recognized mechanisms for the generation and maintenance of such haplotypes (selection for immune response or other advantageous genes, recent mutation, and others), features similar to those exhibited by murine t mutants may be important. Two such features, a positive transmission bias from the male and crossover suppression for a large segment of the human sixth chromosome, are sufficient to explain a number of phenomena and characteristics of the major histocompatibility complex in man. The presence of t-like alleles having these features provides at least partial explanations for the observed linkage disequilibria in different human populations, for much of the observed HLA allele—disease associations (including the “protective” effects of certain alleles), and for the observed higher crossover rate in females than males of genes on the short arm of the sixth chromosome. The presence of such t-like mutants at appreciable frequencies requires a reassessment of chromosomal map distances in this region and of the role of other specific known genes in the evolution of the major histocompatibility complex.