Twelve HLA-DR6-related DRB1 alleles and associated DR, DQ haplotypes in traditional Australians and other populations of Asia-Oceania

Abstract

The relative distributions of 12 HLA-DR6-related HLA-DRB1 alleles in indigenous populations of Australia, Melanesia, Polynesia, Micronesia, and northern and southern China have been determined by analysis of nucleotide sequence polymorphisms in 364 examples of HLA-DR6 positive chromosomes. Oligonucleotide hybridizations of polymerase chain reaction products of HLA-DQA1, DQB1, DRB1 and DRB3 genes generated 24 HLA-DR6-related haplotypes. The study aimed to determine the regional distribution of DR,DQ haplotypes associated with three novel HLA-DR6 alleles, namely DRB1*1408, 1409, and 1410, known to occur in Australian Aborigines, to gain further insights into the molecular phylogeny of these alleles. DRB1*1408 was the most common HLA-DR6 subtype in Oceania, although it was not detected in Chinese. In Australian Aborigines and Papua New Guinean highlanders, DRB1*1408 was associated with DRB3*0202, while in Polynesians and Micronesians it was associated with DRB3*0101. The different haplotype arrangements, together with the near absence of DRB1*1408 in coastal Melanesians, suggest the possibility that two independent mutations have generated DRB1*1408 in Australia and Oceania. DRB1*1409 and 1410 alleles were confined to Australian Aborigines, while DRB1*1407 was found exclusively in Melanesians; DRB1*1401 was the only HLA-DR6 allele represented in all study populations. The population-specific HLA-DR6 alleles and haplotypes have important implications for unrelated bone-marrow donor registries in Australia and Oceania.