在个体中直接测量男性生殖系突变率,使用顺序精子样本
Jonathan E Shoag1, Amoolya Srinivasa2, Caitlin A Loh2
1Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA. jxs218@case.edu.
Nature communications
|March 16, 2025
概括
老化的精子会积累突变,增加遗传多样性和疾病风险. 这项研究直接使用连续的精子样本测量了个体男性生殖系突变率,揭示了与年龄相关的突变负担增加.
科学领域:
- 遗传学 是一个遗传学.
- 生殖生物学 生殖生物学
- 基因组不稳定性 基因组不稳定性
背景情况:
- 随着年龄的增长,人类男性生殖系中累积的突变会导致遗传多样性和疾病.
- 在个人层面上缺乏与衰老相关的男性生殖系突变率在精子中的直接测量.
研究的目的:
- 直接测量精子中个体特定的生殖系突变率.
- 为了研究男性生殖系中与年龄相关的突变积累.
- 评估衰老对精子干细胞池多样性的影响.
主要方法:
- 召回了23名精子捐赠者进行新样本,创建分隔10-33年的顺序样本.
- 利用高保真度双重测序来对整个队列进行突变率分析.
- 采用深度全基因组测序和针对两个个体的序列精子样本的定向验证.
主要成果:
- 精子的直接高保真测序提供了与以前基于家庭的研究一致的突变率.
- 每个个体在连续样本中都显示出精子突变负担的增加,这使得可以测量个体特异性速率.
- 早期克隆突变的马赛克主义保持稳定,这表明衰老并没有显著改变干细胞池的多样性.
结论:
- 序列精子样本的高保真测序允许直接测量个体男性生殖系突变率.
- 衰老与精子突变负担增加有关.
- 精子干细胞池的多样性似乎随着年龄的增长而稳定.
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