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• W2153529713 abstract "Abstract Amino acid replacements in the peptide-binding region (PBR) of the functional major histocompatibility complex (Mhc) genes appear to be driven by balancing selection. Of the various types of balancing selection, we have examined a model equivalent to overdominance that confers heterozygote advantage. As discussed by A. Robertson, overdominance selection tends to maintain alleles that have more or less the same degree of heterozygote advantage. Because of this symmetry, the model makes various testable predictions about the genealogical relationships among different alleles and provides ways of analyzing DNA sequences of Mhc alleles. In this paper, we analyze DNA sequences of 85 alleles at the HLA-A, -B, -C, -DRB1 and -DQB1 loci with respect to the number of alleles and extent of nucleotide differences at the PBR, as well as at the synonymous (presumably neutral) sites. Theory suggests that the number of alleles that differ at the sites targeted by selection (presumably the nonsynonymous sites in the PBR) should be equal to the mean number of nucleotide substitutions among pairs of alleles. We also demonstrate that the nucleotide substitution rate at the targeted sites relative to that of neutral sites may be much larger than 1. The predictions of the presented model are in surprisingly good agreement with the actual data and thus provide means for inferring certain population parameters. For overdominance selection in a finite population at equilibrium, the product of selection intensity (s) against homozygotes and the effective population size (N) is estimated to be 350-3000, being largest at the B locus and smallest at the C locus. We argue that N is of the order of 10(5) and s is several percent at most, if the mutation rate per site per generation is 10(-8)." @default.
• W2153529713 created "2016-06-24" @default.
• W2153529713 creator A5035354959 @default.
• W2153529713 creator A5047528427 @default.
• W2153529713 creator A5049195099 @default.
• W2153529713 date "1992-04-01" @default.
• W2153529713 modified "2023-10-17" @default.
• W2153529713 title "Polymorphism and balancing selection at major histocompatibility complex loci." @default.
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• W2153529713 doi "https://doi.org/10.1093/genetics/130.4.925" @default.
• W2153529713 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1204941" @default.
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