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研究揭示脑皮层中体细胞突变情况
作者:小柯机器人 发布时间:2021/1/14 13:55:26

美国波士顿儿童医院Christopher A. Walsh和哈佛医学院Peter J. Park团队合作取得最新进展。他们利用超深度全基因组测序揭示自闭症和神经型个体大脑皮层的体细胞突变情况。相关论文发表在2021年1月11日出版的《自然-神经科学》杂志上。

他们使用来自59个自闭症谱系障碍(ASD)和15个对照供体的前额叶皮层的超深(~250x)全基因组测序来表征人脑中的体细胞突变(受精后发生的突变)的情况。他们观察到平均每个大脑中有≥4%的细胞存在26个体细胞单核苷酸变异体,并且在编码和假定的调控区域中存在突变。

他们的分析表明,受精后的第一个细胞分裂会产生~3.4个突变,随后的子代会产生2-3个突变。这表明一个典型的个体拥有≥80%的细胞中存在约80个体细胞单核苷酸变异体(相当于每代新生代突变的数量),其中大约一半的个体皮层中,某处具有至少一个可能改变功能的体细胞突变在。与对照组相比,ASD大脑显示神经增强子序列中的体细胞突变过多,表明镶嵌增强子突变可能会导致ASD风险。

附:英文原文

Title: The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing

Author: Rachel E. Rodin, Yanmei Dou, Minseok Kwon, Maxwell A. Sherman, Alissa M. DGama, Ryan N. Doan, Lariza M. Rento, Kelly M. Girskis, Craig L. Bohrson, Sonia N. Kim, Ajay Nadig, Lovelace J. Luquette, Doga C. Gulhan, Peter J. Park, Christopher A. Walsh

Issue&Volume: 2021-01-11

Abstract: We characterize the landscape of somatic mutations—mutations occurring after fertilization—in the human brain using ultra-deep (~250×) whole-genome sequencing of prefrontal cortex from 59 donors with autism spectrum disorder (ASD) and 15 control donors. We observe a mean of 26 somatic single-nucleotide variants per brain present in ≥4% of cells, with enrichment of mutations in coding and putative regulatory regions. Our analysis reveals that the first cell division after fertilization produces ~3.4 mutations, followed by 2–3 mutations in subsequent generations. This suggests that a typical individual possesses ~80 somatic single-nucleotide variants present in ≥2% of cells—comparable to the number of de novo germline mutations per generation—with about half of individuals having at least one potentially function-altering somatic mutation somewhere in the cortex. ASD brains show an excess of somatic mutations in neural enhancer sequences compared with controls, suggesting that mosaic enhancer mutations may contribute to ASD risk.

DOI: 10.1038/s41593-020-00765-6

Source: https://www.nature.com/articles/s41593-020-00765-6

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex