期刊
SCIENCE
卷 359, 期 6375, 页码 550-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aan8690
关键词
-
资金
- NIH [RR19895, RR029676-01, R01 MH100914, U01 MH106876, U01 MH106874, P50 MH106934, R03 CA191421]
- Mayo Clinic Center For Individualized Medicine
Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks postconception) using clonal cell populations. We detected 200 to 400 single-nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of >2% in brain were also present in the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five postzygotic cleavages and calculated a mutation rate of similar to 1.3 mutations per division per cell. Later in development, during neurogenesis, the mutation spectrum shifted toward oxidative damage, and the mutation rate increased. Both neurogenesis and early embryogenesis exhibit substantially more mutagenesis than adulthood.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据