HLA diversity, differentiation, and haplotype evolution in mesoamerican natives

Genetic variation of the Human Leukocyte Antigen region (HLA) in three Amer indian populations from the Southern Mexican state of Oaxaca, the Zapotec, Mixtec and the Mire is examined. Individuals were typed using PCR-SSOP for four class II loci (DRB1, DQA1, DQB1, DPB1)and three class I loci (HLA-A, - B, and -C). Based on known HLA distributions, European admixture ranged fro m 1% to 10%. Individuals with European alleles were excluded from subsequen t analysis. New alleles were revealed at each of the class I loci. In gener al, genotype frequencies were in Hardy-Weinberg equilibrium, although some deviations were detected. Allele frequency distributions at the DRB1. DQA1, DQB1 and HLA-A loci in all populations were more even than expected under neutrality, supporting a model of balancing selection at these loci. A hist ory of directional selection for DPB1 in all three populations was indicate d, as homozygosity values were significantly above expected values. Allele frequency distributions at HLA-B and HLA-C did not differ significantly fro m neutrality expectations. The data also provide evidence from linkage dise quilibrium that strong haplotypic associations are present across the entir e HLA region in each of the populations. Significant overall linkage disequ ilibrium exists between all pairs of loci typed in these populations, excep t those which include the DPB1 locus. These associations exist despite the fact that the recombination fraction between HLA-A, in the class I region, and DQB1, in the class II region, may exceed 0.02. One explanation is that selective pressures are maintaining the relationships between particular al leles at these loci in these populations. These relationships are maintaine d in general across the entire HLA region in the Oaxacan Amerindians, with the exception of DPB1. (C) American Society for Histocompatibility and Immu nogenetics, 2001. Published by Elsevier Science Inc.