ArticleNature communications2023
Limitations of gene editing assessments in human preimplantation embryos.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Empirical optimization of dual-sgRNA design for in vivo CRISPR/Cas9-mediated exon deletion in mice.Computational and structural biotechnology journal · 2026Article
- Advances in single-cell DNA sequencing enable insights into human somatic mosaicism.Nature reviews. Genetics · 2025Review
- Why the hypothesis of embryo selection in IVF/ICSI must finally be reconsidered.Human reproduction open · 2025Article
- Navigating the CRISPR/Cas Landscape for Enhanced Diagnosis and Treatment of Wilson's Disease.Cells · 2024Review
- Various repair events following CRISPR/Cas9-based mutational correction of an infertility-related mutation in mouse embryos.Journal of assisted reproduction and genetics · 2024Article
- Induction of somatic cell haploidy by premature cell division.Science advances · 2024Article
- Efficient repair of human genetic defect by CRISPR/Cas9-mediated interlocus gene conversion.Life medicine · 2023Article
- PGT-A: Houston, we have a problem.Journal of assisted reproduction and genetics · 2023Article
- Retained chromosomal integrity following CRISPR-Cas9-based mutational correction in human embryos.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Article
- Novel embryo selection strategies-finding the right balance.Frontiers in reproductive health · 2023Article
Corrections and comments
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Authors and funding
40 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.6% of preexisting heterozygous loci in control single blastomere samples appear as homozygous after whole genome amplification indicative of allelic dropouts. To overcome these limitations, we validate on-target modifications seen in gene edited human embryos in embryonic stem cells. We show that, in addition to frequent indel mutations, biallelic double-strand breaks can also produce large deletions at the target site. Moreover, some embryonic stem cells show copy-neutral loss of heterozygosity at the cleavage site which is likely caused by interallelic gene conversion. However, the frequency of loss of heterozygosity in embryonic stem cells is lower than in blastomeres, suggesting that allelic dropouts is a common whole genome amplification outcome limiting genotyping accuracy in human preimplantation embryos.
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