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研究揭示克隆性精子镶嵌的发育和时间特征
作者:小柯机器人 发布时间:2021/8/15 20:29:05

美国加州大学圣迭戈分校Joseph G. Gleeson团队揭示克隆性精子镶嵌的发育和时间特征。相关论文于2021年8月12日在线发表在《细胞》杂志上。

通过对射出的精子进行测序,研究人员探索了男性性腺中克隆性镶嵌突变的模式和时间稳定性。通过对健康男性的血液和精子进行300倍的全基因组测序,研究人员发现每次射出的精子平均携带33.3±12.1(平均值±SD)个克隆镶嵌变体,几乎所有的变体都是在连续采样中检测到的,大部分在采样的体组织中没有。

它们的时间稳定性和突变特征表明在胚胎发育过程中起源于一个基本不可改变的干细胞微环境。克隆镶嵌可能为每15个男人中的1个贡献了一个可传播的、预测的致病外显子变体,这代表了这些个体终身的传播威胁和对人类健康的重大负担。

据了解,在整个发育和衰老过程中,人体细胞会积累突变,导致细胞层面的基因组镶嵌和遗传多样性。存在于性腺中的镶嵌突变可以影响个人和后代以及后续世代。

附:英文原文

Title: Developmental and temporal characteristics of clonal sperm mosaicism

Author: Xiaoxu Yang, Martin W. Breuss, Xin Xu, Danny Antaki, Kiely N. James, Valentina Stanley, Laurel L. Ball, Renee D. George, Sara A. Wirth, Beibei Cao, An Nguyen, Jennifer McEvoy-Venneri, Guoliang Chai, Shareef Nahas, Lucitia Van Der Kraan, Yan Ding, Jonathan Sebat, Joseph G. Gleeson

Issue&Volume: 2021-08-12

Abstract: Throughout development and aging, human cells accumulate mutations resulting in genomicmosaicism and genetic diversity at the cellular level. Mosaic mutations present inthe gonads can affect both the individual and the offspring and subsequent generations.Here, we explore patterns and temporal stability of clonal mosaic mutations in malegonads by sequencing ejaculated sperm. Through 300× whole-genome sequencing of bloodand sperm from healthy men, we find each ejaculate carries on average 33.3 ± 12.1(mean ± SD) clonal mosaic variants, nearly all of which are detected in serial sampling,with the majority absent from sampled somal tissues. Their temporal stability andmutational signature suggest origins during embryonic development from a largely immutablestem cell niche. Clonal mosaicism likely contributes a transmissible, predicted pathogenicexonic variant for 1 in 15 men, representing a life-long threat of transmission forthese individuals and a significant burden on human population health.

DOI: 10.1016/j.cell.2021.07.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00883-7

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/