Worldwide genetic diversity at the HLA-DQA1 locus

Genotype, gene, or phenotype frequency data, obtained by PCR analysis with sequence specific oligonucleotide probes at the HLA-DQA1 locus, in 176 population samples, each consisting of 30 or more individuals, from all around the world were analyzed. The sampled populations were assigned to the following nine groups: African, Afro-American, American Native, American Mestizo, Asian, American Caucasian, European Caucasian, Caucasian from other regions, and Pacific Islanders. Observed genotype proportions agreed with Hardy-Weinberg expectations (HWE) in 90 of the 102 populations for which genotype data are available. The 12 discordant population samples were of substantial mixed origin. For these discordant populations, 41 of the 252 (population by genotype) data points showed significant departures of the observed frequencies in comparison to their HWE predictions. The deviations, by and large (38 of the 41), were in the direction of HWE over-estimating the actual genotype frequencies. Total heterozygosity (HT) at a worldwide level was 79%, and varied from 56% in American Natives to >80% in Caucasians. Of the total diversity, 94.4% was due to intra-population and 5.6% to inter-population variation (FST), partitioned into 3.0% inter-population within groups and 2.6% inter-group variation. FST for the locus was high among Africans and American Natives (>9%) and low in Afro-Americans and American Caucasians (<0.5%). The range for allele specific FST was 0.2% to 5.9%, and the lowest value did not correspond to the same allele in all nine groups. A variance component analysis of allele frequencies showed no relationship of the ratio of between/within group variation with the world average frequency of the respective alleles. The first three principal components explained 36.2%, 27.5%, and 22.9% of the total allelic diversity, respectively. For Caucasian and Afro-American samples, the first two PCs formed clusters by groups. In contrast, the American Native, Asian, and Pacific Islander groups showed a greater inter-population diversity, while the corresponding principal component scores of the American Mestizo samples were between American Natives and Caucasians. In aggregate, the analyses indicate that genetic drift in contrast to natural selection, more readily explains the pattern of worldwide diversity at the HLA-DQA1 locus. Am. J. Hum. Biol. 9:735–749, 1997. © 1997 Wiley-Liss, Inc.