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 he re suggest that a consequence of selection at a particular locus may b e the inhibition of recombination through the accumulation of DNA sequ ence polymorphisms. Equivalent 6.4 kb regions from a locus, CL1, locat ed approximately 25-30 kb centromeric of HLA-B, were sequenced for thr ee ancestral haplotypes: A1,B8,DR3; A30,B18,DR3; and A1,B57,DR7. Compa rison of the sequences indicated that the level of DNA sequence polymo rphism was high when compared with the TNF region; approximately 80 si ngle nucleotide differences were found when comparing any two sequence s. In addition, multiple deletions/insertions were present. We believe that the degree of poly morphism within the CL interval may be adequa te to at least partially inhibit recombination between the haplotypes studied.