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.
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We thank all families who participated in the study, the Leuven University Fertility Center for technical assistance and S. Jackmaert for her help with the SNP arrays. We are also grateful to the Mapping Core and Map finishing groups of the Wellcome Trust Sanger Institute for initial BAC clone supply and verification and to the microarray facility of the Flanders Interuniversity Institute for Biotechnology for their help in spotting the arrays. We would like to thank C. Spiessens, E. Legius, T. de Ravel de l'Argentière, H. van Esch and K. Devriendt for the critical reading of the manuscript. This work was made possible by grants from the Institute for the Promotion of Innovation through Science and Technology (IWT-Flanders) (SBO-60848) and GOA/2006/12 and Center of Excellence SymBioSys (Research Council K.U.Leuven EF/05/007) to J.R.V. and Fonds de la Recherche Scientifique to M.V. E.V. was supported by the Institute for the Promotion of Innovation through Science and Technology in Flanders.
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Vanneste, E., Voet, T., Le Caignec, C. et al. Chromosome instability is common in human cleavage-stage embryos. Nat Med 15, 577–583 (2009). https://doi.org/10.1038/nm.1924
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