Diversity of HLA-DR2 in north Indians: the changed scenario after the discovery of DRB1*1506

DRB1*1506, a new allele of DR2, differs from DRB1*1501 only at codon 50 in the second exon, where the nucleotide sequence has changed from GTG to GCG resulting in an amino acid substitution from valine to alanine in DRB1*1506. Since codon 50 was considered non-polymorphic until the discovery of this new allele by sequence-based typing, it became necessary to study what fraction of subjects thought to have DRB1*1501 actually had DRB1*1506. For this purpose, 116 DNA samples with DR2 coming from normal healthy individuals, leprosy patients and childhood tuberculosis patients were amplified using PCR and hybridized with P-32-labeled probes specific for DRB1*1501, DRB1*1502, DRB1*1503, DRB1*1506, DRB1*1601 and DRB1*1602. The oligonucleotide probe for DRB1*1506 was designed to span codons 47-52 based on the published nucleotide sequence. DRB5, DQA1 and DQB1-specific amplifications and hybridizations were also carried out to study the diversity of DR2 haplotypes. It was found that 21% of the samples identified previously as DRB1*1501 were actually DRB1*1506. DRB1*1506 was found to be associated with DQB1*0502 and DQB1*0601. Haplotypes of DRB1*1501, DRB1*1502, DRB1*1506 and DRB1*1602 showed a marked heterogeneity. Besides the rare haplotypes which have not yet been reported in any other populations, haplotypes characteristic of different ethnic groups, such as Croatians, South Chinese and Gypsies, were also found in the North Indians, suggesting the extent of racial admixture and migrations to and from India.