Abstract
The human leukocyte antigen (HLA) region, on chromosome 6p21.3, contains more than 200 genes within this 3 Mb segment, many of which are involved in the function of the immune system (1). The HLA class I (HLA-A, B, and C) and class II (DRB1, DQB1, DPB1, and DQA1) loci encode cell surface heterodimeric proteins that bind antigenic peptides and are the most polymorphic genes in the human genome (see Fig. 1 for HLA region map). Moreover, most of this extensive allelic sequence diversity (i.e., >500 alleles at the HLA-B locus and >300 at the DRB1 locus) is functional and affects peptide binding and recognition of the HLA-peptide complex by the T-cell receptor. Statistical analysis of HLA class I and class II sequences has indicated, based on the ratio of nonsynonymous to synonymous substitutions in the polymorphic sequences encoding the peptide binding cleft of all class I and class II loci, that these polymorphic sequences have been subjected to balancing selection (2, 3). Analyses of allele frequency distributions (4) in various human populations have also supported the action of balancing selection for all HLA loci, with the exception of DPB1 (5). However, the Ewens-Watterson test (4), examining allele frequency distributions, is a relatively insensitive test for balancing selection, and the ratio of nonsynonymous to synonymous substitutions for DPB1 is consistent with balancing selection (6). Therefore, the DPB1 polymorphism is probably not neutral, but the selective pressures operating on DPB1 do appear to be different from those shaping the allele frequency distributions of the other HLA loci.
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© 2005 Humana Press Inc., Totowa, NJ
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Erlich, H.A. (2005). HLA Polymorphism and Disease Susceptibility. In: Peltz, G. (eds) Computational Genetics and Genomics. Humana Press. https://doi.org/10.1007/978-1-59259-930-1_10
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DOI: https://doi.org/10.1007/978-1-59259-930-1_10
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