Uncovering genetic diversity and admixture of British Africans with HLA alleles inferred from whole genome sequencing
Recommended Citation
Liu Y, Meng Z, Adrianto I, Levin AM, Mi QS, Wang Q, and Gui H. Uncovering genetic diversity and admixture of British Africans with HLA alleles inferred from whole genome sequencing. Eur J Hum Genet 2025;33(8):1057-1065.
Document Type
Article
Publication Date
8-1-2025
Publication Title
European journal of human genetics
Abstract
The human leukocyte antigen (HLA) region is highly diverse and plays a crucial role in immune regulation and antigen presentation. Accurate HLA typing is essential for understanding disease susceptibility, transplantation compatibility, and pharmacogenetics. However, its application in African descent populations is challenging due to complex linkage disequilibrium patterns and the lack of ancestry-matched populations in HLA reference panels. Here, we leveraged the latest whole-genome sequencing (WGS) data from UK Biobank African individuals to perform better HLA genotyping, and further utilized allelic and haplotypic data to explore population genetics patterns of this region. With WGS-inferred HLA alleles, we identified specific admixture patterns (predominant West and East African and minor European ancestries) within British African population, revealing their complex evolutionary history. Not only did we reveal the genetic diversity within this population, but also highlighted its differences from African Americans, ancestral Africans, and other global populations. We further identified regional ancestry differences in the HLA genomic region, highlighting discordance between global and local admixture estimates. British Africans also presented unique HLA frequency distributions for both typical and disease-associated alleles or haplotypes. These findings emphasize the need for expanding African-specific HLA reference panel and prove better HLA typing can be achieved by coupling sequencing technologies with computational approaches. The HLA genetic characteristics observed in British Africans provide valuable insights into population-specific immune responses and susceptibility. Overall, this study advances our understanding of HLA diversity and genetic admixture in British African population, with important implications for both disease mechanism and clinical utility.
Medical Subject Headings
Humans; HLA Antigens; Black People; Whole Genome Sequencing; United Kingdom; Alleles; Haplotypes; Genetic Variation; Gene Frequency; Linkage Disequilibrium; African People
PubMed ID
40670583
ePublication
ePub ahead of print
Volume
33
Issue
8
First Page
1057
Last Page
1065
