Chromosome instability is common in human cleavage-stage embryos.
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.
Vanneste
Evelyne
E
Center for Human Genetics, K.U.Leuven, Belgium.
Voet
Thierry
T
Le Caignec
Cédric
C
Ampe
Michèle
M
Konings
Peter
P
Melotte
Cindy
C
Debrock
Sophie
S
Amyere
Mustapha
M
Vikkula
Miikka
M
Schuit
Frans
F
Fryns
Jean-Pierre
JP
Verbeke
Geert
G
D'Hooghe
Thomas
T
Moreau
Yves
Y
Vermeesch
Joris R
JR
D000328:Adult; D000782:Aneuploidy; D001757:Blastomeres / Q000473:pathology; D043171:Chromosomal Instability; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy