Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Somatic mutations reveal widespread mosaicism and mutagenesis in human placentas

View ORCID ProfileTim H. H. Coorens, Thomas R. W. Oliver, Rashesh Sanghvi, Ulla Sovio, Emma Cook, Roser Vento-Tormo, Muzlifah Haniffa, Matthew D. Young, Raheleh Rahbari, Neil Sebire, Peter J. Campbell, View ORCID ProfileD. Stephen Charnock-Jones, Gordon C. S. Smith, Sam Behjati
doi: https://doi.org/10.1101/2021.01.26.428217
Tim H. H. Coorens
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tim H. H. Coorens
Thomas R. W. Oliver
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
2Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rashesh Sanghvi
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ulla Sovio
3Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0SW, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emma Cook
3Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0SW, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roser Vento-Tormo
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Muzlifah Haniffa
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
4Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
5Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, NE1 4LP, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew D. Young
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raheleh Rahbari
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Neil Sebire
6Great Ormond Street Hospital for Children NHS Foundation Trust, NIHR Great Ormond Street Hospital Biomedical Research Centre, London, WC1N 3JH, UK
7UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter J. Campbell
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D. Stephen Charnock-Jones
3Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0SW, UK
8Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for D. Stephen Charnock-Jones
  • For correspondence: dscj1@cam.ac.uk gcss2@cam.ac.uk sb31@sanger.ac.uk
Gordon C. S. Smith
3Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0SW, UK
8Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dscj1@cam.ac.uk gcss2@cam.ac.uk sb31@sanger.ac.uk
Sam Behjati
1Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
2Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
9Department of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dscj1@cam.ac.uk gcss2@cam.ac.uk sb31@sanger.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Clinical investigations of human fetuses have revealed that placentas occasionally harbour chromosomal aberrations that are absent from the fetus1. The basis of this genetic segregation of the placenta, termed confined placental mosaicism, remains unknown. Here, we investigated the phylogeny of human placentas reconstructed from somatic mutations, using whole genome sequencing of 86 placental biopsies and of 106 microdissections. We found that every placental biopsy represented a clonal expansion that is genetically distinct. Biopsies exhibited a genomic landscape akin to childhood cancer, in terms of mutation burden and mutational imprints. Furthermore, unlike any other human normal tissue studied to date, placental genomes commonly harboured copy number changes. Reconstructing phylogenetic relationships between tissues from the same pregnancy, revealed that developmental bottlenecks confined placental tissues, by separating trophectodermal from inner cell mass-derived lineages. Of particular note were cases in which inner cell mass-derived and placental lineages fully segregated within a few cell divisions of the zygote. Such early embryonic bottlenecks may enable the normalisation of zygotic aneuploidy. We observed direct evidence for this in a case of mosaic trisomic rescue. Our findings reveal cancer-like mutagenesis in placental tissues and portray confined mosaicism as the normal outcome of placental development.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted January 27, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Somatic mutations reveal widespread mosaicism and mutagenesis in human placentas
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Somatic mutations reveal widespread mosaicism and mutagenesis in human placentas
Tim H. H. Coorens, Thomas R. W. Oliver, Rashesh Sanghvi, Ulla Sovio, Emma Cook, Roser Vento-Tormo, Muzlifah Haniffa, Matthew D. Young, Raheleh Rahbari, Neil Sebire, Peter J. Campbell, D. Stephen Charnock-Jones, Gordon C. S. Smith, Sam Behjati
bioRxiv 2021.01.26.428217; doi: https://doi.org/10.1101/2021.01.26.428217
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Somatic mutations reveal widespread mosaicism and mutagenesis in human placentas
Tim H. H. Coorens, Thomas R. W. Oliver, Rashesh Sanghvi, Ulla Sovio, Emma Cook, Roser Vento-Tormo, Muzlifah Haniffa, Matthew D. Young, Raheleh Rahbari, Neil Sebire, Peter J. Campbell, D. Stephen Charnock-Jones, Gordon C. S. Smith, Sam Behjati
bioRxiv 2021.01.26.428217; doi: https://doi.org/10.1101/2021.01.26.428217

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3688)
  • Biochemistry (7783)
  • Bioengineering (5673)
  • Bioinformatics (21267)
  • Biophysics (10574)
  • Cancer Biology (8170)
  • Cell Biology (11929)
  • Clinical Trials (138)
  • Developmental Biology (6757)
  • Ecology (10394)
  • Epidemiology (2065)
  • Evolutionary Biology (13853)
  • Genetics (9702)
  • Genomics (13063)
  • Immunology (8136)
  • Microbiology (19976)
  • Molecular Biology (7841)
  • Neuroscience (43032)
  • Paleontology (318)
  • Pathology (1278)
  • Pharmacology and Toxicology (2258)
  • Physiology (3350)
  • Plant Biology (7221)
  • Scientific Communication and Education (1311)
  • Synthetic Biology (2000)
  • Systems Biology (5533)
  • Zoology (1127)