Chromosome instability is common in human cleavage-stage embryos

Area of Science:

• Genetics
• Developmental Biology
• Reproductive Medicine

Background:

• Chromosome instability is a known hallmark of cancer development.
• Its role in early human embryogenesis has been less understood.

Purpose of the Study:

• To investigate the prevalence and nature of chromosome instability in early human embryos.
• To identify the impact of this instability on human fecundity and genetic disorders.

Main Methods:

• Development of a novel array-based method for single-cell genome-wide analysis.
• Screening for copy number variations and loss of heterozygosity in cleavage-stage embryos.

Main Results:

• Most cleavage-stage embryos exhibit mosaicism for aneuploidies and uniparental disomies.
• Frequent segmental deletions, duplications, and amplifications were observed.
• Evidence suggests breakage-fusion-bridge cycles contribute to genomic alterations.

Conclusions:

• Post-zygotic chromosome instability is a significant factor in early human development.
• This instability contributes to low human fecundity and is a major cause of constitutional chromosomal disorders.