Genome sequencing of normal cells reveals developmental lineages and mutational processes

Sam Behjati, Meritxell Huch, Ruben van Boxtel, Wouter Karthaus, David C Wedge, Asif U Tamuri, Iñigo Martincorena, Mia Petljak, Ludmil B Alexandrov, Gunes Gundem, Patrick S Tarpey, Sophie Roerink, Joyce Blokker, Mark Maddison, Laura Mudie, Ben Robinson, Serena Nik-Zainal, Peter Campbell, Nick Goldman, Marc van de WeteringEdwin Cuppen, Hans Clevers, Michael R Stratton

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)422-5
Number of pages4
JournalNature
Volume513
Issue number7518
DOIs
Publication statusPublished - 18 Sep 2014

Keywords

  • Animals
  • Biological Clocks
  • Cell Division
  • Cell Lineage
  • Cells, Cultured
  • Clone Cells
  • Embryo, Mammalian
  • Genome
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutagenesis
  • Mutation
  • Mutation Rate
  • Organoids
  • Phylogeny
  • Sequence Analysis, DNA
  • Tail

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