Gene frequency and linkage disequilibrium analysis of HLA-DRB1*04 haplotypes in a South Wales population

HLA-DRB1*04 allele frequencies have been determined in 184 HLA-DR4-positive unrelated blood donors from the South Wales area, using group-specific polymerase chain reaction (PCR) amplification and hybridization with sequence-specific oligonucleotide probes, PCR amplification with sequence-specific primers, and PCR single-strand conformation polymorphism analysis. Eight of the fifteen known HLA-DR4 sequences were detected in this study. Linkage disequilibrium analysis of HLA-DRB1*04 and HLA-B, -DR and -DQ alleles revealed distinct haplotypic associations for all the major alleles detected in this population, including the novel linkage of HLA-B55 with DRB1*0407. These results are relevant to the role of HLA-DRB1*04 haplotypes in determining allogeneic histocompatibility and disease susceptibility.