Person: Zhang, Hailei
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Zhang
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Hailei
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Zhang, Hailei
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Publication RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues(American Association for the Advancement of Science (AAAS), 2019-06-06) Yizhak, Keren; Aguet, Francois; Kim, Jaegil; Hess, Julian; Kubler, Kirsten; Grimsby, Jonna; Frazer, Ruslana; Zhang, Hailei; Haradhvala, Nicholas; Rosebrock, Daniel; Livitz, Dimitri; Li, Xiao; Arich-Landkof, Eila; Shoresh, Noam; Stewart, Chip; Segre, Ayelet; Branton, Philip A; Polak, Paz; Ardlie, Kristin; Getz, GadHow somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA-sequencing data from ~6,700 samples across 29 normal tissues reveals multiple somatic variants, demonstrating that macroscopic clones can be found in many normal tissues. We confirm that sun-exposed skin, esophagus, and lung have a higher mutation burden than other tested tissues, suggesting that environmental factors can promote somatic mosaicism. Mutation burden is associated with both age and tissue-specific cell proliferation rate, highlighting that mutations accumulate over time and number of cell divisions. Finally, we find that normal tissues harbor mutations in known cancer genes and hotspots. This study provides a broad view of macroscopic clonal expansion in human tissues, thus serving as the basis to associate clonal expansion with environmental factors, aging and risk of disease.