Uncovering genetic diversity and admixture of British Africans with HLA alleles inferred from whole genome sequencing

作者：Yunjia Liu, Ze Meng, Indra Adrianto, Albert M. Levin, Qing‐Sheng Mi, Qiang Wang, Hongsheng Gui · 发表于：European Journal of Human Genetics · 年份：2025 · DOI：10.1038/s41431-025-01888-9 · 被引用次数：3 · 研究领域：T-cell and B-cell Immunology、Systemic Lupus Erythematosus Research、HIV Research and Treatment

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 c...