Cancer Centre and Institute of Translational Medicine, Ministry of Education Frontiers Science Center for Precision Oncology, Faculty of Health Sciences, University of Macau, Macau, China.
Cancer Centre and Institute of Translational Medicine, Ministry of Education Frontiers Science Center for Precision Oncology, Faculty of Health Sciences, University of Macau, Macau, China
Life Sci Alliance. 2022 May 20;5(9). doi: 10.26508/lsa.202101319. Print 2022 Sep.
Deleterious variants in DNA damage repair (DDR) system can cause genome instability and increase cancer risk. In this study, we analyzed the deleterious variants in DDR system in 16 ethnic human populations. From the genetic variants in 169 DDR genes involved in nine DDR pathways collected from 158,612 individuals of different ethnic background, we identified 1,781 deleterious variants in 81 DDR genes in eight DDR pathways (https://genemutation.fhs.um.edu.mo/dbddr-global/). Our analysis showed although the quantity of deleterious variants was loaded at a similar level, the landscape of the variants differed substantially among different populations that two-third of the variants were present in single ethnic populations, and the rest was mostly shared between the populations with closer geographic and genetic relationship. The highly ethnic-specific DDR deleterious variation suggests its potential relationship with different disease susceptibility in ethnic human populations.
DNA 损伤修复 (DDR) 系统中的有害变异可导致基因组不稳定并增加癌症风险。在这项研究中，我们分析了 16 个人类族群的 DDR 系统中的有害变异。从涉及九个 DDR 途径的 169 个 DDR 基因的遗传变异中，我们在八个 DDR 途径中鉴定出 81 个 DDR 基因中的 1781 个有害变异（https://genemutation.fhs.um.edu.mo/dbddr-global/）。我们的分析表明，尽管有害变异的数量加载在相似的水平上，但变异的模式在不同人群中存在显著差异，三分之二的变异存在于单一族群中，其余的则主要存在于地理和遗传关系较近的人群之间。高度特定于族群的 DDR 有害变异表明其可能与不同族群的疾病易感性有关。
