Diversity associated with the second expressed H L A - D R B locus in the human population

Abstract

Although diversity within the HLA-DRB region is predominantly focused in the DRB1 gene, the second expressed DRB loci, DRB3, DRB4, and DRB5, also exhibit variation. Within DRB1 ^* 15 or DRB1 ^* 16 haplotypes, four new variants were identified: 1) two new DRB5 alleles, DRB5^* 0104 and DRB5^* 0204, 2) a haplotype carrying a DRB1 ^* 15 or ^* 16 allele without the usual accompanying DRB5 allele, and 3) a haplotype carrying a DRB5^* 0101 allele without a DRB1 ^* 15 or ^* 16 allele. The evolutionary origins of these haplotypes were postulated based on their associations with the DRB6 pseudogene. Within HLA haplotypes which carry DRB3, a new DRB3 ^* 0205 allele and one unusual DRB3 association were identified. Finally, two new null DRB4 alleles are described: DRB4 ^* 0201N, which exhibits a deletion in the second exon, and a second allele, DRB4 ^* null, which lacks the second exon completely. Gene conversion-like events and variation in the number of functional genes through reciprocal recombination and inactivation contribute to the diversity observed in the second expressed HLA-DRB loci.