Coorens Tim H H, Oh Ji Won, Choi Yujin Angelina, Lim Nam Seop, Zhao Boxun, Voshall Adam, Abyzov Alexej, Antonacci-Fulton Lucinda, Aparicio Samuel, Ardlie Kristin G, Bell Thomas J, Bennett James T, Bernstein Bradley E, Blanchard Thomas G, Boyle Alan P, Buenrostro Jason D, Burns Kathleen H, Chen Fei, Chen Rui, Choudhury Sangita, Doddapaneni Harsha V, Eichler Evan E, Evrony Gilad D, Faith Melissa A, Fazzio Thomas G, Fulton Robert S, Garber Manuel, Gehlenborg Nils, Germer Soren, Getz Gad, Gibbs Richard A, Hernandez Raquel G, Jin Fulai, Korbel Jan O, Landau Dan A, Lawson Heather A, Lennon Niall J, Li Heng, Li Yan, Loh Po-Ru, Marth Gabor, McConnell Michael J, Mills Ryan E, Montgomery Stephen B, Natarajan Pradeep, Park Peter J, Satija Rahul, Sedlazeck Fritz J, Shao Diane D, Shen Hui, Stergachis Andrew B, Underhill Hunter R, Urban Alexander E, VonDran Melissa W, Walsh Christopher A, Wang Ting, Wu Tao P, Zong Chenghang, Lee Eunjung Alice, Vaccarino Flora M
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
European Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI), Cambridge, UK.
Nature. 2025 Jul;643(8070):47-59. doi: 10.1038/s41586-025-09096-7. Epub 2025 Jul 2.
From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.
从受精开始，人体细胞的DNA序列就会出现变异，即体细胞突变。这些合子后突变源于DNA复制和修复过程中的内在错误，以及暴露于诱变剂。体细胞突变与某些疾病有关，但对于健康人体组织中突变的频率、类型和模式的基本了解一直有限。这主要是因为个体中携带特定体细胞变异的细胞比例很小，使得它们比遗传变异更难检测。在此，我们描述了人类组织体细胞嵌合网络，其目的是创建一个体细胞突变及其克隆模式的参考目录，涵盖来自150名非患病捐赠者的19个不同组织部位，并开发新技术和计算工具来检测体细胞突变并评估其表型后果，包括克隆扩增。这一策略能够全面检查人体的突变图谱，并为疾病中的体细胞突变提供比较基线。这将有助于深入了解一生中的体细胞突变和克隆扩增，以及它们在健康、衰老以及疾病中的作用。
