为了研究合子后突变（PZM）的起源和功能后果，研究人员生成了一个多组织的PZM图谱，涵盖了948个捐赠者的54个组织和细胞类型。近一半的组织样本之间的突变负担的变化可以通过测量的技术和生物效应来解释，9%可以归因于捐赠者的特定影响。通过对PZM的系统发育重建，研究人员发现它们的类型和预测的功能影响在产前发育、跨组织和生殖细胞的生命周期中是不同的。因此，为了充分了解遗传变异的后果，需要有解释整个身体和整个生命期的影响的方法。
据悉，PZM在受精后立即开始在人类基因组中累积，但PZM如何以及何时影响发育和终身健康仍不清楚。
附：英文原文
Title: The origins and functional effects of postzygotic mutations throughout the human life span
Author: Nicole B. Rockweiler, Avinash Ramu, Liina Nagirnaja, Wing H. Wong, Michiel J. Noordam, Casey W. Drubin, Ni Huang, Brian Miller, Ellen Z. Todres, Katinka A. Vigh-Conrad, Antonino Zito, Kerrin S. Small, Kristin G. Ardlie, Barak A. Cohen, Donald F. Conrad
Issue&Volume: 2023-04-14
Abstract: Postzygotic mutations (PZMs) begin to accrue in the human genome immediately after fertilization, but how and when PZMs affect development and lifetime health remain unclear. To study the origins and functional consequences of PZMs, we generated a multitissue atlas of PZMs spanning 54 tissue and cell types from 948 donors. Nearly half the variation in mutation burden among tissue samples can be explained by measured technical and biological effects, and 9% can be attributed to donor-specific effects. Through phylogenetic reconstruction of PZMs, we found that their type and predicted functional impact vary during prenatal development, across tissues, and through the germ cell life cycle. Thus, methods for interpreting effects across the body and the life span are needed to fully understand the consequences of genetic variants.
DOI: abn7113
Source: https://www.science.org/doi/10.1126/science.abn7113