Journal
NATURE
Volume 513, Issue 7518, Pages 422-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature13448
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Funding
- Wellcome Trust [077012/Z/05/Z]
- Kadoorie Charitable Foundation
- Louis-Jeantet Foundation
- Marie Curie IEF fellowship [EU/236954]
- ERC [232814]
- Netherlands Genomics Initiative [935.12.003]
- Centre for Biomedical Genetics, Utrecht
- EMBO Long Term Fellowship [ALTF-1287-2012]
- Wellcome Trust Intermediate Clinical Fellowship [WT100183MA]
- Wellcome-Beit Prize Fellowship
- Wellcome Trust Research Training Fellowship for Clinicians
- Wellcome Trust Senior Research Fellowship in Clinical Science
- European Research Council (ERC) [232814] Funding Source: European Research Council (ERC)
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The somatic mutations present in the genome of a cell accumulate over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree(1), the number of divisions that each cell has undergone and the mutational processes that have been operative(2). Here we describe whole genomes of clonal lines(3) derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal, demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.
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