Studies of the major histocompatibility complex (MHC) in mouse indicat
e that the recombination sites are not randomly distributed and their
occurrence is haplotype dependent. No data concerning haplotype-specif
ic recombination sites in human are available due to the low number of
informative families. To investigate haplotype-specific recombination
sites in human MHC, we here describe an approach based on identificat
ion of recombinant haplotypes derived from one conserved haplotype at
the population level. The recombination sites were mapped by comparing
polymorphic markers between the recombinant and assumed original hapl
otypes. We tested this approach on the extended haplotype HLA A3; B47;
BfF; C4A*1; C4B*Q0; DR7, which is most suitable for this analysis. F
irst, it carries a number of rare markers, and second, the haplotype,
albeit rare in the general population, is frequent in patients with 21
-hydroxylase (21OH) defect. We observed recombinants derived from this
haplotype in patients with 21OH defect. All these haplotypes had the
centromeric part (from Bf to DR) identical to the original haplotype,
but they differed in HLA A and B. We therefore assumed that they under
went recombinations in the segment that separates the Bf and HLA B gen
es. Polymorphic markers indicated that all break points mapped to two
segments near the TNF locus. This approach makes possible the mapping
of preferential recombination sites in different haplotypes.