A Haplotype Study of HLA Complex with Special Reference to the HLA‐DR Series and to Bf. C2 and Glyoxalase I Polymorphisms

Abstract

Fifty-three French families were typed for alleles at seven loci of the HLA complex (HLA-A, -B, -C, -DR, -Bf, -C2 and -GLO) and 212 haplotypes were demonstrated. Eleven recombinations were observed (two A/B, two A/C, two B/Bf, one Bf/D and four D/GLO). The linkage disequilibrium was calculated not only between two alleles (delta) but between three, four...seven alleles (D). In order to compare the intensity of D values in the various haplotypes, the influence of the differences in gene frequencies was eliminated by the introduction of the standardized Ds (Ds = D/D max). The number of haplotypes in disequilibrium is relatively limited since most of the significant Ds involved about 17 haplotypes. For some haplotypes, the disequilibrium covered the whole distance from A to GLO but the stronger disequilibrium concerns the C to Bf or C to DR segment. Three hypotheses (isolation, admixture of population and selection) concerning the formation and maintenance of the disequilibria are discussed.

Inherited predisposition to iridocyclitis with juvenile rheumatoid arthritis: selectivity among HLA-DR5 haplotypes.

“…Some 20-30% of all HLA haplotypes show linkage disequilibrium that generally extends between HLA-B and -DR and includes alleles of the four HLA-linked complement loci (22,29,30). Occasionally, the linkage group involves an HLA-A allele and a glyoxalase allele,tt the latter being mapped centromeric to HLA-D. Several mechanisms have been suggested to account for the phenomenon of linkage disequilibrium.…”

Cells that express viral antigens but lack H-2 determinants are not lysed by immune thymus-derived lymphocytes but are lysed by other antiviral immune attack mechanisms.

“…Hence, the lack of reported restriction may be due to the fact that at least one of the four H antigens was shared [the minimal requirement for lysis in the mouse system (40)] in the patients assayed. HLA antigens are shared by many members of the human race, and some serologically defined HLA antigens crossreact (41)(42)(43). Furthermore, when lymphocyte killing of virus-infected cells was studies in humans, the targets were xenogeneic cells (35)(36)(37)(38)(39).…”

A linkage disequilibrium map of the MHC region based on the analysis of 14 loci haplotypes in 50 French families

“…2 The phenomenon of linkage disequilibrium has become a prominent characteristic of the MHC since the early descriptions of the multilocus polymorphism. 3,4 Since then, numerous 'extended' haplotypes have been described in human populations all around the world. 5,6 Their likely conservation in human populations has led some authors to define the notion of 'ancestral' haplotypes, preserved for various possible reasons from early human populations.…”