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Nature. 2014 Sep 18;513(7518):422-425. doi: 10.1038/nature13448. Epub 2014 Jun 29.

Genome sequencing of normal cells reveals developmental lineages and mutational processes.

Author information

1
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
2
Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK.
3
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
4
Present address: Wellcome Trust / Cancer Research UK Gurdon Institute, Tennis Court Road, CB2 1QN, Cambridge, UK.
5
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
6
East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.
#
Contributed equally

Abstract

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, the number of divisions that each cell has undergone and the mutational processes that have been operative. Here we describe whole genomes of clonal lines 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.

PMID:
25043003
PMCID:
PMC4227286
DOI:
10.1038/nature13448
[Indexed for MEDLINE]
Free PMC Article
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