Recombination Fractions in the Hla System Based on the Data Set ‘Provinces Françaises’: Indications of Haplotype‐specific Recombination Rates

Abstract

In the large genetic survey "Provinces Françaises' the recombination fractions in the HLA system have been estimated by a family analysis programme (FAP). A total of 1332 families were analysed and in general the findings were in agreement with recombination fractions reported previously. The maternal recombination rates were on average 1.8 times higher than the corresponding ones for males. The comparison of the recombination fractions with the corresponding physical distances suggests the existence of hot spots of recombination. The analysis did not show deviations from expected values for HLA-A and B alleles on HLA-A/B recombinant haplotypes. However, analysis of HLA-B/DR recombinant haplotypes showed a skewed distribution of B and DR alleles. The significance of the findings is difficult to evaluate as all results are estimated numbers and frequencies but a manual analysis of the recombinant families confirmed the observations. HLA-B/DR recombinant haplotypes carried often HLA-DR3 and DR11 whereas DR2 and DR7 were more rarely present on recombinant haplotypes. DR4 had an increased incidence on BF/DR recombinant haplotypes but not on A/B or B/BF recombinant haplotypes. Some of the haplotypes with the strongest linkage disequilibria as A1,B8,DR3 and A3,B7,DR2 seem to be less frequently involved in recombinations than other haplotypes. Variations of recombination rates depending on certain alleles or haplotypes might partially explain the conservation of some haplotypes or part of haplotypes in Caucasoids.

Meiotic Recombination Hotspots

“…As in mice, some regions cross over more often in specific haplotypes (139). Some effort has been made to map HIA breakpoints (115), but so far the data have been limited by a lack of appropriate crosses.…”

?Both man & bird & beast?: comparative organization of MHC genes

“…In contrast, cross-overs have been described thoughout the DP-DQ region. Non-random recombination positions (hotspots) may be observed elsewhere in the class I and class III regions (Thomsen et al 1994). One such locus, a meiotic hotspot with enhanced homologous …”

An approach to mapping haplotype-specific recombination sites in human MHC class III

“…Hence, the data concerning human haplotypes are very limited. Haplotype-specific recombination rates were observed in a study of French families (Thomsen et al 1994), but the analysis included only the classical HLA antigens. More detailed mappings have been presented by Martin and co-workers (1995) and Crouau-Roy and co-workers (1993), but the haplotypespecificity of these sites is not known.…”