A Region Centromeric of the Major Histocompatibility Complex Class I Region Is as Highly Polymorphic as HLA-B: Implications for Recombination

Two hallmarks of the MHC are the high degree of polymorphism apparent at multiple loci and ''linkage disequilibrium.'' The data presented here suggest that a consequence of selection at a particular locus may be the inhibition of recombination through the accumulation of DNA sequence polymorphisms. Equivalent 6.4 kb regions from a locus, CL1, located approximately 25-30 kb centromeric of HLA-B, were sequenced for three ancestral haplotypes: A1,B8,DR3; A30,B18,DR3; and A1,B57,DR7. Comparison of the sequences indicated that the level of DNA sequence polymorphism was high when compared with the TNF region; approximately 80 single nucleotide differences were found when comparing any two sequences. In addition, multiple deletions/insertions were present. We believe that the degree of poly morphism within the CL interval may be adequate to at least partially inhibit recombination between the haplotypes studied.