title: Two new HLA DRB1 alleles found in African Americans: implications for balancing selection at positions 57 and 86.
abstract: Two new DRB1 alleles have been identified (DRB1*0303 and DRB1*0805) in African Americans that differ from known DRB1 alleles only by a glycine to valine exchange at position 86. The novel DRB1*0303 allele, found in one individual, has the same DQA1*0401-DQB1*04 haplotype as DRB1*0302, suggesting that it may be a recent diversification of *0302. The novel DRB1*0805 allele, identified in 4 individuals, was found on two haplotypes, sharing a DQA1*0501-DQB1*0301 haplotype with DRB1*0804, and a DQA1*0102-DQB1*0602 haplotype found with DRB1*0801 in some African populations. DRB1*0805 differs from *0804 only at position 57 and differs from *0801 only at position 86. Assuming that DRB1*0801 and DRB1*0802 are ancestral, based on their distribution in various human populations, DRB1*0805 may have been generated twice by two independent mutations or gene conversion events at each of these positions. Alternatively, DRB1*0805 may have arisen from a single gene conversion event (or mutation) and recombined to generate multiple DR-DQ haplotypes. These findings increase the number of DRB1 allelic pairs that differ only at position 86 to 9, suggesting strong balancing selection at this position. A number of DRB1 alleles for DR8 and DR4 also differ only at position 57, a site previously postulated to be strongly influenced by balancing selection in DQB1 alleles by phylogenetic analysis.
authors.affiliation: Department of Human Genetics, Roche Molecular Systems, Emeryville, CA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Apple
authors.forename: H A
authors.initials: HA
authors.lastname: Erlich
mesh_terms: D000349:Africa; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D004247:DNA / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D014481:United States; D001741:Black or African American
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D004247:DNA