Diversity in HLA-DR4-related DR,DQ haplotypes in Australia, Oceania, and China.
The relative distributions of 12 HLA-DR4-related DRB1 alleles in indigenous populations of Australia, Melanesia, Micronesia, Polynesia, and northern and southern China have been determined by analysis of oligonucleotide hybridization patterns of 406 examples of HLA-DR4. DRB1*0405 and DRB1*0410 were common DR4 alleles in Australian aborigines and in Melanesians, while DRB1*0403 was the predominant DR4 allele in coastal Melanesians, Micronesians, and Polynesians; DRB1*0406 was confined to Chinese. A novel DR4 allele, found in 30% of DR4-positive Australian aborigines but exclusive to one aboriginal population, was a combination of DRB1*04 and 0803 nucleotide sequences and was carried on a haplotype with DR4-like DQ linkage arrangements. DQA1 and DQB1 typing generated 12 DR4-related haplotypes; the population distributions of these reflected the ancestral affinities of aborigines and Melanesians, the overlaying of coastal Melanesia with pre-Polynesian DR4 alleles and the colonization of Micronesia by an independent, non-Polynesian group. DR4-related autoimmune disorders such as rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM) are virtually unknown in indigenous populations of Australia and Oceania and this study confirmed that high-risk RA determinants, Dw4 and Dw14, occurred rarely. However, the DQw8 allele, thought particularly to predispose to IDDM, was present in the majority of DR4-positive Polynesians and Micronesians.
Gao
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Human Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra.
Serjeantson
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SW
D000483:Alleles; D000595:Amino Acid Sequence; D001315:Australia; D001483:Base Sequence; D002681:China; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010139:Pacific Islands; D016133:Polymerase Chain Reaction; D000095283:Australian Aboriginal and Torres Strait Islander Peoples
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes