作者
Teng Gao, Maria Eleni Kastriti, Viktor Ljungström, Andreas Heinzel, Arthur S Tischler, Rainer Oberbauer, Po-Ru Loh, Igor Adameyko, Peter J Park, Peter V Kharchenko
发表日期
2023/11
期刊
Nature genetics
卷号
55
期号
11
页码范围
1901-1911
出版商
Nature Publishing Group US
简介
Genetic mutations accumulate in an organism’s body throughout its lifetime. While somatic single-nucleotide variants have been well characterized in the human body, the patterns and consequences of large chromosomal alterations in normal tissues remain largely unknown. Here, we present a pan-tissue survey of mosaic chromosomal alterations (mCAs) in 948 healthy individuals from the Genotype-Tissue Expression project, augmenting RNA-based allelic imbalance estimation with haplotype phasing. We found that approximately a quarter of the individuals carry a clonally-expanded mCA in at least one tissue, with incidence strongly correlated with age. The prevalence and genome-wide patterns of mCAs vary considerably across tissue types, suggesting tissue-specific mutagenic exposure and selection pressures. The mCA landscapes in normal adrenal and pituitary glands resemble those in tumors arising …
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