Report from the extended HLA‐DPA1 ~ promoter ~ HLA‐DPB1 haplotype of the 18th international HLA and immunogenetics workshop

Abstract

The primary goal of the HLA‐DPA1 ~ promoter ~ HLA‐DPB1 haplotype component of the 18th IHIWS was to characterise the extended haplotypes within the HLA‐DP region and survey the extent of genetic diversity in this region across human populations. In this report, we analysed single‐nucleotide polymorphisms (SNPs) in 255 subjects from 6 different cohorts. The results from the HLA‐DP haplotype component have validated findings from the initial pilot study. SNPs in this region were inherited in strong linkage, particularly HLA‐DPA1, SNP‐linked promoter haplotypes and motifs in exon 2 of HLA‐DPB1. We reported 17 SNP‐linked haplotypes in the promoter region. Together with HLA‐DPA1 and HLA‐DPB1 alleles, they formed 74 distinct extended HLA‐DP haplotypes in 438 sequences. We also observed the presence of region‐specific alleles and promoter haplotypes. Our approach involved phasing extended SNPs including promoter SNPs, HLA‐DPA1 and HLA‐DPB1 alleles, in a 22 kb region, GRCh38/hg38 (chr6:33,064,111‐33,086,679), followed by clustering of these SNPs as one extended haplotype. This hierarchical clustering revealed four major clades, suggesting that haplotypes within each clade may have diverged from a common ancestral haplotype and undergone similar evolutionary processes. The correlation between HLA‐DPA1 and the promoter region raises questions about the role of HLA‐DPA1 antigen in the heterodimer. This finding requires validation on a larger sample size specifically designed for anthropological analysis. Nevertheless, the results from this study highlight the clinical potential of selecting better‐matched donors for patients awaiting haematopoietic stem cell transplants from genetically overlapping groups that share common ancestral haplotypes.