Nature: 父母年龄越大, 子女自发性遗传突变发生率越高

欢迎点击「PaperRss」↑关注我们！

1人类序列差异与 年龄、性别、突变类型、基因组有关

英国《自然》杂志近日在线发表的一篇遗传学论文，报告了迄今为止最大规模的人类自发性基因突变研究。该研究同时显示，父母年龄越大，尤其是父亲年龄越大，子女的自发性遗传突变（DNM）发生率越高。这项对人类基因组序列多样性突变过程的分析，对未来医学研究至关重要。

欢迎点击「PaperRss」↑关注我们！

基因突变可以是自发的，也可以是诱发的，这两者之间其实并没有本质上的不同。通常自发性突变指家族当中首次出现的基因变化，由父母其中一方的卵子或精子突变导致。欢迎点击「PaperRss」↑关注我们！

为了解父母年龄和性别因素是如何引起自发性遗传突变差异的，位于冰岛的解码基因公司deCODE研究人员丹尼尔·古德贾森及其同事，对14688名冰岛人开展了全基因组序列分析，具体包括1548名个体及其父母，对于其中的225名个体，至少包含他们的一名子女。

在分析中，研究团队鉴定出108778个高质量自发性遗传突变，平均每个家庭70.3个。他们发现，来自母亲的自发性遗传突变数量，按年龄每年增加0.37个，而来自父亲的则按年龄每年增加1.51个，前者仅占后者的四分之一。研究团队还发现，簇状突变数量随母亲年龄增长的速度高于随父亲年龄增长的速度，而且母亲自发性遗传突变簇的基因组跨度大于父亲的。此外，来自母亲的自发性遗传突变类型会随着年龄发生显著变化。

研究人员表示，这项最新的分析帮助人们了解造成人类基因组序列多样性的突变过程，而这在医学、遗传学和演化学的研究中非常关键。（来源：科技日报 张梦然）欢迎点击「PaperRss」↑关注我们！

---

Parental influence on human germline de novo mutations in 1,548 trios from Iceland 

Nature ( IF 40.137 ) Pub Date : 2017-09-20 , DOI: 10.1038/nature24018 

Hákon Jónsson, Patrick Sulem, Birte Kehr, Snaedis Kristmundsdottir, Florian Zink, Eirikur Hjartarson, Marteinn T. Hardarson, Kristjan E. Hjorleifsson, Hannes P. Eggertsson, Sigurjon Axel Gudjonsson, Lucas D. Ward, Gudny A. Arnadottir, Einar A. Helgason, Hannes Helgason, Arnaldur Gylfason, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Thorunn Rafnar, Mike Frigge, Simon N. Stacey, Olafur Th. Magnusson, Unnur Thorsteinsdottir, Gisli Masson, Augustine Kong, Bjarni V. Halldorsson, Agnar Helgason, Daniel F. Gudbjartsson, Kari Stefansson
Abstract:

The characterization of mutational processes that generate sequence diversity in the human genome is of paramount importance both to medical genetics and to evolutionary studies. To understand how the age and sex of transmitting parents affect de novo mutations, here we sequence 1,548 Icelanders, their parents, and, for a subset of 225, at least one child, to 35× genome-wide coverage. We find 108,778 de novo mutations, both single nucleotide polymorphisms and indels, and determine the parent of origin of 42,961. The number of de novo mutations from mothers increases by 0.37 per year of age (95% CI 0.32–0.43), a quarter of the 1.51 per year from fathers (95% CI 1.45–1.57). The number of clustered mutations increases faster with the mother’s age than with the father’s, and the genomic span of maternal de novo mutation clusters is greater than that of paternal ones. The types of de novo mutation from mothers change substantially with age, with a 0.26% (95% CI 0.19–0.33%) decrease in cytosine–phosphate–guanine to thymine–phosphate–guanine (CpG>TpG) de novo mutations and a 0.33% (95% CI 0.28–0.38%) increase in C>G de novo mutations per year, respectively. Remarkably, these age-related changes are not distributed uniformly across the genome. A striking example is a 20 megabase region on chromosome 8p, with a maternal C>G mutation rate that is up to 50-fold greater than the rest of the genome. The age-related accumulation of maternal non-crossover gene conversions also mostly occurs within these regions. Increased sequence diversity and linkage disequilibrium of C>G variants within regions affected by excess maternal mutations indicate that the underlying mutational process has persisted in humans for thousands of years. Moreover, the regional excess of C>G variation in humans is largely shared by chimpanzees, less by gorillas, and is almost absent from orangutans. This demonstrates that sequence diversity in humans results from evolving interactions between age, sex, mutation type, and genomic location.

欢迎点击「PaperRss」↑关注我们！

---

往期文章推荐：（直接点击浏览）

免责声明

部分文章和信息来源于互联网，不代表本订阅号赞同其观点并对其真实性负责。如转载内容涉及版权等问题，小编将迅速采取删除措施。本订阅号原创内容，转载时，请注明来源“PaperRSS”。

温馨提示

为方便小木虫里研究生们的科研生活交流。PaperRss微信公众平台特建立了两个全国博士就业交流群。建群半年已来，两群成员已经达到700多人。成员包含了美国、欧洲、日本、清华北大、中科院名校、地方大学博士以及企业经理，HR等；涉及各学科领域方向。欢迎各位新人直接搜索 IGDB2010 刚哥微信号申请加入，入群请务必注明“姓名-单位-研究方向”。