Immunogenetics of HLA-B: SNP, allele, and haplotype diversity in populations from different continents and ancestry backgrounds

HLA. 2023 Jun;101(6):634-646. doi: 10.1111/tan.15043. Epub 2023 Apr 2.

Abstract

HLA-B is among the most variable gene in the human genome. This gene encodes a key molecule for antigen presentation to CD8+ T lymphocytes and NK cell modulation. Despite the myriad of studies evaluating its coding region (with an emphasis on exons 2 and 3), few studies evaluated introns and regulatory sequences in real population samples. Thus, HLA-B variability is probably underestimated. We applied a bioinformatics pipeline tailored for HLA genes on 5347 samples from 80 different populations, which includes more than 1000 admixed Brazilians, to evaluate the HLA-B variability (SNPs, indels, MNPs, alleles, and haplotypes) in exons, introns, and regulatory regions. We observed 610 variable sites throughout HLA-B; the most frequent variants are shared worldwide. However, the haplotype distribution is geographically structured. We detected 920 full-length haplotypes (exons, introns, and untranslated regions) encoding 239 different protein sequences. HLA-B gene diversity is higher in admixed populations and Europeans while lower in African ancestry individuals. Each HLA-B allele group is associated with specific promoter sequences. This HLA-B variation resource may improve HLA imputation accuracy and disease-association studies and provide evolutionary insights regarding HLA-B genetic diversity in human populations.

Keywords: HLA-B; NGS; evolutionary aspects; haplotypes; polymorphism; variability; worldwide populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Gene Frequency
  • HLA-B Antigens / genetics
  • Haplotypes
  • Humans
  • Immunogenetics*
  • Polymorphism, Single Nucleotide*

Substances

  • HLA-B Antigens