HLA class I allele distributions in six Pacific/Asian populations: evidence of selection at the HLA-A locus

• Published in: Tissue antigens 1999-04, Vol.53 (4), p.311-319
• Main Authors: Bugawan, T.L., Mack, S.J., Stoneking, M., Saha, M., Beck, H.P., Erlich, H.A.
• Format: Article
• Language: English
• Subjects: Alleles; Asian Continental Ancestry Group; Filipino; Gene Frequency; Genetics, Population; HLA-A; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-B; Humans; Indonesian; Malay; Molecular Sequence Data; Molucca; new allele; Nusa Tengara; Pacific Ocean; PCR; Phylogeny; PNG; selection
• ISSN: 0001-2815; 1399-0039
• DOI: 10.1034/j.1399-0039.1999.530401.x

: The distributions of HLA‐A alleles in six Pacific/Asian populations, Malay, Papua New Guinea (PNG) Highlands, two Indonesian groups, and two PNG Lowland groups, as well as the distribution of the HLA‐B alleles in the PNG Highlands population, were determined using polymerase chain reaction (PCR) immobilized sequence‐specific oligonucleotide (SSO) probe typing methods. The allele frequency distributions at the HLA class II loci, DRB1, DQB1 and DPB1 were also determined by PCR/SSO methods in an additional study of the same populations. In most of these populations, the HLA‐A*2402 allele was the most frequent, attaining a frequency of 0.78 in the PNG Highlands. A*1101 was the next most frequent allele, followed in frequency by the *3401 allele. The HLA‐B*1506, *4001, *5601 and *5602 alleles comprised 73% of the allele diversity at the B‐locus in the PNG Highlands. Two previously unreported HLA‐A alleles were identified in Indonesians and Malays, based on novel probe reactivity patterns. Cloning and sequencing identified these as A*1104 and *2410. Sequence comparisons show that these new alleles differ at codon 187 from their putative parental alleles (*1101 and *2403) by dinucleotide changes in the first two codon positions. These changes involve a Thr to Arg (CG to AC) and an Arg to Thr substitution (AC to CG) at position 187; residues at this position participate in pocket A of the peptide binding groove. Comparison of the HLA‐A allele frequency distributions indicate that Malays are the most diverse (heterozygosity (h)=0.88) and the PNG Highlanders are, by far, the least diverse (h=0.37) of the groups studied. However, the diversity of B‐locus alleles in the PNG Highlanders (h=0.91) was greater than that observed at the A‐locus of any of the populations reported here. The remarkably high allele frequency of A*2402 in the PNG Highlands could reflect founder effects and population bottlenecks, genetic drift, or positive directional selection. The distribution of the HLA‐B locus alleles and class II alleles, as well as mtDNA sequence data in the PNG Highlands indicates a reasonably high level of diversity at other loci, arguing that the high frequency of A*2402 cannot be attributed entirely to founder effects, bottlenecks, or drift and suggests the operation of positive selection for the A*2402 allele in this population Note.