title: Genome sequencing of normal cells reveals developmental lineages and mutational processes.
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.
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.|Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Behjati
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.|Present address: Wellcome Trust / Cancer Research UK Gurdon Institute, Tennis Court Road, CB2 1QN, Cambridge, UK.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Huch
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: van Boxtel
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Karthaus
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Wedge
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Asif U
authors.initials: AU
authors.lastname: Tamuri
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Inigo
authors.initials: I
authors.lastname: Martincorena
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Mia
authors.initials: M
authors.lastname: Petljak
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Ludmil B
authors.initials: LB
authors.lastname: Alexandrov
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Gunes
authors.initials: G
authors.lastname: Gundem
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tarpey
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Roerink
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Joyce
authors.initials: J
authors.lastname: Blokker
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Maddison
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Mudie
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Robinson
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.|East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Serena
authors.initials: S
authors.lastname: Nik-Zainal
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Campbell
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Goldman
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D002455:Cell Division; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology* / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D016678:Genome / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D009940:Organoids / Q000166:cytology / Q000378:metabolism; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013623:Tail / Q000166:cytology