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The mutational landscape of human somatic and germline cells

机译：人体细胞和种细胞的突变景观

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摘要

Over the course of an individual's lifetime, normal human cells accumulate mutations~(1). Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially. SBS18, which potentially reflects oxidative damage~(2), and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The rate of mutation was lowest in spermatogonia, the stem cells from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma.
机译：在个体的寿命过程中，正常人体细胞积累突变〜（1）。在这里，我们使用来自同一个人的多个样本从SOMA和种系中的29个细胞类型中的突变比较。两个无处不在的突变签名，SBS1和SBS5 / 40，占大多数细胞类型中的大多数获得的突变，但它们的绝对和相对贡献变化得很大。 SBS18可能反映氧化损伤〜（2），以及归因于外源性和内源性暴露的几种另外的签名是对细胞类型的亚群的突变。突变率在精子中最低，生成精子的干细胞和人群中最遗传变异的源于思考。这是由于普遍存在的突变过程的低速率，并且可以部分地归因于基础精子寄生虫的细胞分裂的低速率。这些结果突出了种系和躯体的维护中的相似之处和差异。

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  • 来源
    《Nature》 |2021年第7876期|381-386|共6页
  • 作者

    Luiza Moore; Alex Cagan; Tim H H Coorens; Matthew D C Neville; Rashesh Sanghvi; Mathijs A Sanders; Thomas R W Oliver; Daniel Leongamornlert; Peter Ellis; Ayesha Noorani; Thomas J Mitchell; Timothy M Butler; Yvette Hooks; Anne Y Warren; Mette Jorgensen; Kevin J Dawson; Andrew Menzies; Laura ONeill; Calli Latimer; Mabel Teng; Ruben van Boxtel; Christine A Iacobuzio-Donahue; Inigo Martincorena; Rakesh Heer; Peter J Campbell; Rebecca C Fitzgerald; Michael R Stratton; Raheleh Rahbari;

  • 作者单位

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute|Department of Pathology Cambridge University Hospitals NHS Foundation Trust;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute|Department of Hematology Erasmus University Medical Center;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute|Department of Pathology Cambridge University Hospitals NHS Foundation Trust;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute|Inivata;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute|Department of Surgery University of Cambridge;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Department of Pathology Cambridge University Hospitals NHS Foundation Trust;

    Great Ormond Street Hospital for Children NHS Foundation Trust;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Princess Máxima Center for Pediatric Oncology and Oncode Institute;

    Department of Pathology Sol Goldman Pancreatic Cancer Research Center Johns Hopkins University School of Medicine|Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University|Newcastle Urology Freeman Hospital Newcastle upon Tyne Hospitals NHS Foundation Trust;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    MRC Cancer Unit University of Cambridge;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

    Cancer Ageing and Somatic Mutation (CASM) Wellcome Sanger Institute;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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