人类DNA不匹配修复基因中的生殖系致病变体的进化起源
Huijun Lei1,2,3, Jiaheng Li1, Bojin Zhao1
1Ministry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China.
Human genomics
|January 30, 2024
概括
与癌症风险相关的不匹配修复 (MMR) 基因中的致病变体最近起源于人类进化. 这些MMR变种并没有在物种中保存,但是在古代人类基因组中发现的.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 不匹配修复 (MMR) 系统对于保持基因组稳定性至关重要.
- 在MMR基因中的生殖系致病变体 (PVs) 导致MMR缺陷,显著增加癌症风险.
- 了解人类MMR PVs的进化起源对于理解癌症中的MMR缺陷至关重要.
研究的目的:
- 研究人类不匹配修复 (MMR) 基因中的生殖系致病变体 (PVs) 的进化起源.
- 为了确定人类MMR的PV是否起源于跨物种的保护或最近的人类进化.
主要方法:
- 从ClinVar中获取了MMR基因变异,并使用遗传学分析分析了100个脊椎动物基因组,用于跨物种的保护.
- 检查了超过5000个古人类基因组 (45,045年至100年前) 的MMR PVs,使用调用重新缩放的古老测序数据的变体.
主要成果:
- 在99个非人类脊椎动物基因组中,在现代人类中发现的3369个MMR PVs中没有发现跨物种保护的证据.
- 在现代人和古代人类之间共享的MMR PVs的一个子集被确定,主要是在过去的10,000年内,显示出类似的定量模式.
结论:
- 人类不匹配修复基因中的致病变体在最近的人类进化历史中出现.
- 这些发现表明,最近的人类进化,而不是古老的跨物种保护,是导致癌症风险的MMR常见PVs的来源.
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