序列保存增强剂类元素对人类复杂特征的遗传影响.
Xiang Zhu1,2,3, Shining Ma4,5, Wing Hung Wong6,7
1Department of Statistics, The Pennsylvania State University, 326 Thomas Building, University Park, 16802, PA, USA. xiangzhu@psu.edu.
Genome biology
|January 3, 2024
概括
识别功能性DNA元素,结合序列保护和生物化学活性,有助于理解复杂的特征和疾病. 这种方法改善了对肥胖和精神分裂症等疾病的基因优先级.
科学领域:
- 基因组学和生物信息学
- 进化生物学 进化生物学
- 人类的复杂特征 人类的复杂特征
背景情况:
- 大多数人类全基因组关联研究 (GWAS) 的发现都在非编码DNA中,阻碍了机理学理解和临床应用.
- 进化保存和生化活性非编码序列是解释GWAS结果的潜在关键.
- 缺乏对这些功能元素在人类组织和特征的系统检查.
研究的目的:
- 开发一种可扩展的策略,用于识别具有高人鼠序列保护和增强器类活性的功能元素.
- 评估这些元素在复杂的人类特征的遗传性和遗传结构中的作用.
- 使用集成的进化和生化数据,对复杂特征的候选基因进行优先排序.
主要方法:
- 开发了一种基于序列保护和增强剂类生物化学活性来识别功能元素的策略.
- 将该策略应用于106种人类组织/细胞类型的313个表观基因组数据集.
- 综合发现与来自欧洲 (EUR) 和东亚 (EAS) 祖先的468个GWAS数据集.
主要成果:
- 鉴定到的功能元素显示了许多特征的遗传性和因果变异的显著组织特异性丰富.
- 与缺乏序列保护的增强剂相比,丰富性更强.
- 优先考虑的候选基因与体重指数 (BMI) 和精神分裂症相关,包括新的关联.
结论:
- 序列保存,增强剂类元素显著影响各种人体组织的复杂特征.
- 综合战略提供了一种可通用的方法来阐明人类疾病的遗传基础.
- 这种方法增强了对复杂特征背后的监管机制的理解.
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