2022/08/02
论文
论文标题：Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
作者：Taejeong Bae, Liana Fasching, Yifan Wang, Joo Heon Shin, Milovan Suvakov, Yeongjun Jang, Scott Norton, Caroline Dias, Jessica Mariani, et al.
期刊：Science
发表时间：2022/07/28
数字识别码：10.1126/science.abm6222
摘要：We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.
