精子测序显示了男性生殖系中广泛的阳性选择
Matthew D C Neville1, Andrew R J Lawson1, Rashesh Sanghvi1
1Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Hinxton, UK.
Nature
|October 8, 2025
概括
精子突变随着年龄的增长而增加后代的疾病风险. 男性生殖系的阳性选择导致病原性突变的风险增加2至3倍,影响老年男性的精子3至5%.
科学领域:
- 遗传学
- 人类生物学
- 生殖医学
背景情况:
- 精子中的生殖基因突变可以遗传,可能导致发育障碍.
- 之前的研究在鉴定精子突变时受到测序错误率的限制.
- 精子生成过程中突变的积极选择是疾病流行的一个已知的因素.
研究的目的:
- 用先进的测序来量化不同年龄段的精子中的突变积累.
- 在男性生殖系中确定积极选择的基因.
- 评估生殖线选择对遗传疾病风险的影响.
主要方法:
- 使用NanoSeq双重测序方法对81个精子样本进行测序.
- 精子样本的深度向和外体测序以确定生殖系编码突变.
- 对突变积累率和积极选择特征的分析.
主要成果:
- 观察到与衰老相关的每年1. 67个突变的线性积累.
- 鉴定了超过35,000个生殖系编码突变,其中有40个基因处于显著的积极选择状态.
- 积极选择的基因与发育和癌症倾向性障碍有关.
- 在中年到老年男性的精子中发现了3-5%的致病突变.
结论:
- 精子生成涉及积极选择,这增加了传染致病突变的风险.
- 晚年父亲的年龄与后代出现某些遗传疾病的风险显著增加.
- 这项研究提供了关于生殖线选择动态和与年龄相关的疾病风险的新见解.
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