Two new HLA DRB1 alleles found in African Americans: implications for balancing selection at positions 57 and 86.

Two new DRB1 alleles have been identified (DRB10303 and DRB10805) in African Americans that differ from known DRB1 alleles only by a glycine to valine exchange at position 86. The novel DRB10303 allele, found in one individual, has the same DQA10401-DQB104 haplotype as DRB10302, suggesting that it may be a recent diversification of 0302. The novel DRB10805 allele, identified in 4 individuals, was found on two haplotypes, sharing a DQA10501-DQB10301 haplotype with DRB10804, and a DQA10102-DQB10602 haplotype found with DRB10801 in some African populations. DRB10805 differs from 0804 only at position 57 and differs from 0801 only at position 86. Assuming that DRB10801 and DRB10802 are ancestral, based on their distribution in various human populations, DRB10805 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.