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dc.contributor.authorRouhani, Foad
dc.contributor.authorNik-Zainal, Serena
dc.contributor.authorWuster, Arthur
dc.contributor.authorLi, Yilong
dc.contributor.authorConte, Nathalie
dc.contributor.authorKoike-Yusa, Hiroko
dc.contributor.authorKumasaka, Natsuhiko
dc.contributor.authorVallier, Ludovic
dc.contributor.authorYusa, Kosuke
dc.contributor.authorBradley, Allan
dc.date.accessioned2018-09-20T12:06:50Z
dc.date.available2018-09-20T12:06:50Z
dc.date.issued2016-04
dc.identifier.issn1553-7390
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280540
dc.description.abstractThe accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCells, Cultured
dc.subjectHumans
dc.subjectCell Lineage
dc.subjectMutation
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectYoung Adult
dc.subjectInduced Pluripotent Stem Cells
dc.titleMutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.
dc.typeArticle
prism.issueIdentifier4
prism.publicationDate2016
prism.publicationNamePLoS Genet
prism.startingPagee1005932
prism.volume12
dc.identifier.doi10.17863/CAM.27908
dcterms.dateAccepted2016-02-22
rioxxterms.versionofrecord10.1371/journal.pgen.1005932
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-04-07
dc.contributor.orcidRouhani, Foad [0000-0002-2334-1305]
dc.contributor.orcidNik-Zainal, Serena [0000-0001-5054-1727]
dc.contributor.orcidVallier, Ludovic [0000-0002-3848-2602]
dc.contributor.orcidBradley, Allan [0000-0002-2349-8839]
dc.identifier.eissn1553-7404
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_PC_12009)
cam.issuedOnline2016-04-07


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International