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 polymorphism within the CL interval may be adequate to at least partially inhibit recombination between the haplotypes studied.
Abraham
L J
LJ
Institute for Molecular Genetics and Immunology, Royal Perth Hospital, Western Australia.
Grimsley
G
G
Leelayuwat
C
C
Townend
D C
DC
Pinelli
M
M
Christiansen
F T
FT
Dawkins
R L
RL
D001483:Base Sequence; D002503:Centromere; D005805:Genes, MHC Class I / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015235:HLA-B Antigens; D014409:Tumor Necrosis Factor-alpha