State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Center for Evolutionary Biology, School of Life Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 220 Handan Road, Yangpu District, Shanghai, 200433, China.
Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Xuhui District, Shanghai, 200031, China.
Brief Bioinform. 2024 Jul 25;25(5). doi: 10.1093/bib/bbae451.
Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis-expression quantitative loci (sb-cis-eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb-cis-eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes.
性别的基因表达在不同的人群中存在差异；然而，其潜在的遗传基础和分子机制在很大程度上仍是未知的。在这里，我们通过分析 90 名新疆维吾尔族（XJU）和 40 名无关汉族个体的全基因组测序数据和转录组数据，探讨了遗传背景对人类转录组中性别差异的影响及其对欧亚混合人群（XJU）的遗传效应。我们在 XJU 中鉴定出 302 个性别偏倚表达基因和 174 个性别偏倚顺式表达数量性状基因座（sb-cis-eQTLs），这些基因富集于先天免疫相关功能，表明免疫功能存在性别差异。值得注意的是，大约四分之一的 sb-cis-eQTLs 与遗传成分具有很强的相关性；即具有相似遗传背景的人群往往表现出相似的性别偏倚基因表达模式。我们的分析进一步表明，遗传混合导致了一定程度的性别偏倚基因表达。有趣的是，染色体相互作用的分析表明，X 染色体作用于常染色体免疫相关基因，部分解释了性别偏倚表型差异的原因。我们的工作从遗传混合的角度扩展了性别偏倚基因表达的知识，并填补了常染色体和 X 染色体相互作用塑造性别偏倚表型的探索空白。值得注意的是，我们证明了性染色体不能完全解释免疫相关表型的性别分化。
