Liu Yunjia, Meng Ze, Adrianto Indra, Levin Albert M, Mi Qing-Sheng, Wang Qiang, Gui Hongsheng
Psychiatry Research and Behavioral Health Services, Henry Ford Health, Detroit, MI, USA.
Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Heath, Detroit, MI, USA.
Eur J Hum Genet. 2025 Jul 16. doi: 10.1038/s41431-025-01888-9.
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.
人类白细胞抗原（HLA）区域高度多样化，在免疫调节和抗原呈递中发挥着关键作用。准确的HLA分型对于理解疾病易感性、移植相容性和药物遗传学至关重要。然而，由于复杂的连锁不平衡模式以及HLA参考面板中缺乏与非洲血统人群匹配的群体，其在非洲血统人群中的应用具有挑战性。在此，我们利用英国生物银行非洲个体的最新全基因组测序（WGS）数据进行更好的HLA基因分型，并进一步利用等位基因和单倍型数据来探索该区域的群体遗传学模式。通过WGS推断的HLA等位基因，我们在英国非洲人群中确定了特定的混合模式（主要是西非和东非血统以及少量欧洲血统），揭示了他们复杂的进化历史。我们不仅揭示了该人群中的遗传多样性，还突出了其与非裔美国人、非洲祖先以及其他全球人群的差异。我们进一步确定了HLA基因组区域的区域血统差异，突出了全球和本地混合估计之间的不一致。英国非洲人在典型和疾病相关的等位基因或单倍型方面也呈现出独特的HLA频率分布。这些发现强调了扩大非洲特异性HLA参考面板的必要性，并证明通过将测序技术与计算方法相结合可以实现更好的HLA分型。在英国非洲人中观察到的HLA遗传特征为群体特异性免疫反应和易感性提供了有价值的见解。总体而言，这项研究推进了我们对英国非洲人群中HLA多样性和遗传混合的理解，对疾病机制和临床应用都具有重要意义。
