Copy number variation is a fundamental aspect of the placental genome

PLoS Genet. 2014 May 1;10(5):e1004290. doi: 10.1371/journal.pgen.1004290. eCollection 2014 May.


Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000 N polyploid trophoblast giant cells (TGCs) of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR). UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(D)J recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / genetics
  • Cell Differentiation / genetics
  • DNA Copy Number Variations*
  • Female
  • Gene Deletion
  • Genome*
  • Humans
  • Neurogenesis
  • Placenta / metabolism*
  • Polyploidy
  • Pregnancy
  • Stochastic Processes