祖先特异性的调节和疾病架构很可能是由于细胞类型特异性的基因与环境相互作用
Juehan Wang1,2, Steven Gazal1,2,3
1Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
medRxiv : the preprint server for health sciences
|October 31, 2023
概括
遗传变异对疾病表现出祖先特异性的影响. 在祖先之间差异表达的基因与细胞类型特定的基因与环境相互作用有关,影响疾病风险和复杂的特征.
科学领域:
- 基因组学就是基因组学.
- 人类遗传学 人类遗传学
- 分子生物学分子生物学
背景情况:
- 全基因组关联研究 (GWAS) 揭示了祖先特定变异效应大小.
- 了解这些差异是解读人类疾病和复杂特征的遗传基础的关键.
研究的目的:
- 在细胞类型层面描述具有祖先差异表达 (ancDE) 的基因.
- 调查ancDE基因附近的变体是否富含具有祖先特异效应的疾病变体.
主要方法:
- 来自东亚 (EAS) 和欧洲 (EUR) 个体的外周血液单核细胞的单细胞RNA测序.
- 对31种疾病和EAS和EUR种群中复杂特征的祖先匹配GWAS数据的分析.
主要成果:
- ancDE基因通常是细胞类型特异的,并富含环境相互作用基因.
- 接近ancDE基因的变异与祖先特定的疾病效应大小有关.
- 有证据表明,细胞类型特定的基因与环境 (GxE) 相互作用影响疾病架构.
结论:
- ancDE基因及其相关变体在祖先特异性疾病影响中发挥作用.
- GxE相互作用可能是观察到的祖先特异性表达和GWAS发现的基础,如MCL1和淋巴细胞计数所示.
- 多样化,大规模的单细胞和GWAS数据集对于进一步了解遗传变异对人类疾病的影响至关重要.
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