Chromosome instability is common in human cleavage-stage embryos

Evelyne Vanneste, Thierry Voet, Cédric Le Caignec, Michèle Ampe, Peter Konings, Cindy Melotte, Sophie Debrock, Mustapha Amyere, Miikka Vikkula, Frans Schuit, Jean-Pierre Fryns, Geert Verbeke, Thomas D'Hooghe, Yves Moreau, Joris R Vermeesch, Evelyne Vanneste, Thierry Voet, Cédric Le Caignec, Michèle Ampe, Peter Konings, Cindy Melotte, Sophie Debrock, Mustapha Amyere, Miikka Vikkula, Frans Schuit, Jean-Pierre Fryns, Geert Verbeke, Thomas D'Hooghe, Yves Moreau, Joris R Vermeesch

Abstract

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.

References

    1. EMBO J. 1998 Jan 2;17(1):325-33
    1. Am J Med Genet. 1999 Jan 29;82(3):265-74
    1. Prenat Diagn. 2005 Oct;25(10):894-900
    1. Nature. 2000 Aug 10;406(6796):641-5
    1. J Med Genet. 2001 Aug;38(8):497-507
    1. Eur J Hum Genet. 2001 Jul;9(7):539-47
    1. Fertil Steril. 2005 Nov;84(5):1328-34
    1. Prenat Diagn. 2004 Aug;24(8):638-43
    1. Cytogenet Genome Res. 2005;111(3-4):237-44
    1. Hum Genet. 2000 Feb;106(2):210-7
    1. Nucleic Acids Res. 2007;35(3):e15
    1. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8995-9000
    1. Genome Res. 2007 Sep;17(9):1296-303
    1. Hum Reprod. 1997 Apr;12(4):780-4
    1. PLoS One. 2007 Jun 27;2(6):e558
    1. Hum Reprod. 2003 Jan;18(1):182-8
    1. Am J Hum Genet. 2008 Feb;82(2):261-82
    1. Hum Reprod. 2008 Mar;23(3):478-80
    1. Nature. 1997 Apr 10;386(6625):623-7
    1. Nucleic Acids Res. 2006 May 12;34(9):e68
    1. Hum Reprod. 2006 Jan;21(1):223-33
    1. Hum Reprod Update. 2002 Jul-Aug;8(4):333-43
    1. Nature. 1988 Mar 31;332(6163):459-61
    1. Fertil Steril. 2005 Nov;84(5):1395-400
    1. Hum Reprod. 2008 Apr;23(4):741-55
    1. J Med Genet. 2008 Mar;45(3):147-54
    1. Chromosome Res. 2004;12(6):627-40
    1. Hum Reprod. 2008 Mar;23(3):499-503
    1. Hum Reprod. 2004 Dec;19(12):2849-58
    1. Mol Hum Reprod. 2008 Feb;14(2):117-25
    1. Hum Mol Genet. 2003 Sep 1;12(17):2153-65
    1. Mol Hum Reprod. 2000 Nov;6(11):1055-62
    1. Nature. 2004 Nov 18;432(7015):338-41
    1. PLoS One. 2007 Dec 12;2(12):e1306
    1. Trends Genet. 2008 Feb;24(2):64-9
    1. Prenat Diagn. 2006 Apr;26(4):333-9

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera