Ning Zhilin, Tan Xinjiang, Yuan Yuan, Huang Ke, Pan Yuwen, Tian Lei, Lu Yan, Wang Xiaoji, Qi Ruicheng, Lu Dongsheng, Yang Yajun, Guan Yaqun, Mamatyusupu Dolikun, Xu Shuhua
Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China.
Natl Sci Rev. 2023 Mar 21;10(4):nwad077. doi: 10.1093/nsr/nwad077. eCollection 2023 Apr.
It remains unknown and debatable how European-Asian-differentiated alleles affect individual phenotypes. Here, we made the first effort to analyze the expression profiles of highly differentiated genes with eastern and western origins in 90 Uyghurs using whole-genome (30× to 60×) and transcriptome data. We screened 921 872 east-west highly differentiated genetic variants, of which ∼4.32% were expression quantitative trait loci (eQTLs), ∼0.12% were alternative splicing quantitative trait loci (sQTLs), and ∼0.12% showed allele-specific expression (ASE). The 8305 highly differentiated eQTLs of strong effects appear to have undergone natural selection, associated with immunity and metabolism. European-origin alleles tend to be more biasedly expressed; highly differentiated ASEs were enriched in diabetes-associated genes, likely affecting the diabetes susceptibility in the Uyghurs. We proposed an admixture-induced expression model to dissect the highly differentiated expression profiles. We provide new insights into the genetic basis of phenotypic differentiation between Western and Eastern populations, advancing our understanding of the impact of genetic admixture.
欧亚分化的等位基因如何影响个体表型仍然未知且存在争议。在此，我们首次尝试利用全基因组（30×至60×）和转录组数据，分析90名维吾尔族人中具有东西方不同起源的高度分化基因的表达谱。我们筛选出921872个东西方高度分化的遗传变异，其中约4.32%是表达数量性状位点（eQTL），约0.12%是可变剪接数量性状位点（sQTL），约0.12%表现为等位基因特异性表达（ASE）。8305个具有强效应的高度分化eQTL似乎经历了自然选择，与免疫和代谢相关。欧洲起源的等位基因往往表达更偏向性；高度分化的ASE在糖尿病相关基因中富集，可能影响维吾尔族人的糖尿病易感性。我们提出了一个混合诱导表达模型来剖析高度分化的表达谱。我们为西方和东方人群之间表型分化的遗传基础提供了新的见解，推进了我们对基因混合影响的理解。
