Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
Division of Psychiatry, Faculty of Health and Medical Sciences, Medical School, The University of Western Australia, Crawley, WA, Australia.
Sci Rep. 2024 Feb 9;14(1):3392. doi: 10.1038/s41598-024-53986-1.
The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals. A cohort of 570 unrelated healthy citizens of the UAE volunteered to provide samples for Whole Genome Sequencing and Whole Exome Sequencing. The definition of the HLA alleles was achieved through the application of the bioinformatics tools, HLA-LA and xHLA. Subsequently, the findings from this study were compared with other local and international datasets. A broad range of HLA alleles in the UAE population, of which some were previously unreported, was identified. A comparison with other populations confirmed the current population's unique intertwined genetic heritage while highlighting similarities with populations from the Middle East region. Some disease-associated HLA alleles were detected at a frequency of > 5%, such as HLA-B51:01, HLA-DRB103:01, HLA-DRB115:01, and HLA-DQB102:01. The increase in allele homozygosity, especially for HLA class I genes, was identified in samples with a higher level of genome-wide homozygosity. This highlights a possible effect of consanguinity on the HLA homozygosity. The HLA allele distribution in the UAE population showcases a unique profile, underscoring the need for tailored databases for traditional activities such as unrelated transplant matching and for newer initiatives in precision medicine based on specific populations. This research is part of a concerted effort to improve the knowledge base, particularly in the fields of transplant medicine and investigating disease associations as well as in understanding human migration patterns within the Arabian Peninsula and surrounding regions.
人类白细胞抗原 (HLA) 分子是免疫反应的核心，与各种疾病的表型和诱导药物毒性有关。此外，HLA 分子在呈递抗原方面的作用显著影响移植结果。本研究的目的是使用下一代测序方法检查阿联酋 (UAE) 人群中 HLA 等位基因多样性的程度，并涵盖更大的个体队列。一个由 570 名无关的阿联酋健康公民组成的队列自愿提供样本进行全基因组测序和全外显子组测序。通过应用生物信息学工具 HLA-LA 和 xHLA 来确定 HLA 等位基因的定义。随后，将本研究的结果与其他本地和国际数据集进行比较。在阿联酋人群中发现了广泛的 HLA 等位基因，其中一些以前未报道过。与其他人群的比较证实了当前人群独特的交织遗传遗产，同时突出了与中东地区人群的相似之处。一些与疾病相关的 HLA 等位基因的频率超过了 5%，例如 HLA-B51:01、HLA-DRB103:01、HLA-DRB115:01 和 HLA-DQB102:01。在全基因组杂合度较高的样本中，发现了等位基因纯合度的增加，尤其是 HLA Ⅰ类基因。这突出了近亲繁殖对 HLA 纯合度的可能影响。阿联酋人群的 HLA 等位基因分布展示了独特的特征，强调了针对传统活动（如无关移植匹配）和基于特定人群的新型精准医学倡议需要定制数据库。这项研究是提高知识库的努力的一部分，特别是在移植医学和调查疾病关联以及了解阿拉伯半岛和周边地区人类迁移模式的领域。
