Unexpected CRISPR on-target effects
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LOH can result from complex genomic rearrangements such as inversions, large insertions, translocations, chromosome loss, and IH-HR with crossover.
“Loss-of-heterozygosity (LOH) can also be the result of more complex genomic rearrangements like inversions, large insertions, translocations, chromosome loss and even IH-HR with crossover, whereby a large piece of one parental allele is integrated by the other parental chromosome at the on-target cut-site (15).”
From Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos (2021) · cites this paper as [15]
CRISPR-Cas9-induced deletions larger than the PCR fragment can eliminate one or both primer annealing sites, leading to amplification of only one allele and a false impression of unsuccessful targeting or a single homozygous event.
“CRISPR-Cas9-induced deletions larger than these fragments in either direction would eliminate one or both PCR primer annealing sites.This in turn can lead to amplification of only one allele, giving the false impression that targeting was unsuccessful or that there is a single homozygous event at the on-target site (9,10,15).”
From Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos (2021) · cites this paper as [15]
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- Authors
- Lee, H., & Kim, J.-S.
- Affiliations
- Institute for Basic Science (KR)
- Seoul National University (KR)
- Corresponding author
- Kim, Jin-Soo
- Venue
- Nature Biotechnology
- Published
- 2018-07-30
- Volume
- 36
- Issue
- 8
- Pages
- 703-704
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2883859031
- Cited by
- 46
- References
- 10
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 10 · 2019: 5 · 2018: 1
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- CRISPR/Cas9, on-target effects, off-target effects, genome editing, large deletions, inversion, insertion, DNA double-strand breaks
- MeSH terms
- Humans, Chromosome Inversion, Mutagenesis, Insertional, Gene Deletion, CRISPR-Cas Systems
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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