Chromosome instability is common in human cleavage-stage embryos

Nat Med. 2009 May;15(5):577-83. doi: 10.1038/nm.1924. Epub 2009 Apr 26.


Chromosome instability is a hallmark of tumorigenesis. This study establishes that chromosome instability is also common during early human embryogenesis. A new array-based method allowed screening of genome-wide copy number and loss of heterozygosity in single cells. This revealed not only mosaicism for whole-chromosome aneuploidies and uniparental disomies in most cleavage-stage embryos but also frequent segmental deletions, duplications and amplifications that were reciprocal in sister blastomeres, implying the occurrence of breakage-fusion-bridge cycles. This explains the low human fecundity and identifies post-zygotic chromosome instability as a leading cause of constitutional chromosomal disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aneuploidy
  • Blastomeres / pathology
  • Chromosomal Instability*
  • Embryo, Mammalian / abnormalities*
  • Embryo, Mammalian / pathology
  • Female
  • Fertilization in Vitro / adverse effects*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Loss of Heterozygosity*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Pregnancy

Associated data

  • GEO/GPL3718
  • GEO/GPL6928
  • GEO/GPL6929
  • GEO/GSE11663