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Genetic compensation: A phenomenon in search of mechanisms
Open accessAbstract
Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.
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“Even in the case of a true gene knockout, however, the time required for a single cell clone to propagate might be sufficient for cells to establish genetic compensation, thereby altering expression patterns of related proteins to make up for the loss of one protein [4].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [4]
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Metadata
- Authors
- El-Brolosy, M. A., & Stainier, D. Y. R.
- Affiliations
- Max Planck Institute for Heart and Lung Research (DE)
- Corresponding author
- Stainier, Didier Y. R.
- Venue
- PLOS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-07-13
- Volume
- 13
- Issue
- 7
- Pages
- e1006780
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC5509088
- OpenAlex
- W2735720719
- Cited by
- 829
- References
- 156
- Citations by year
- 2026: 60 · 2025: 84 · 2024: 89 · 2023: 91 · 2022: 114 · 2021: 109 · 2020: 120 · 2019: 104 · 2018: 54 · 2017: 4
- FWCI
- 7.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Max-Planck-Gesellschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- genetic compensation, dosage compensation, gene knockout, gene knockdown, off-target effects, EGFL7, transcriptional regulation, post-transcriptional regulation, molecular mechanisms
- MeSH terms
- Animals, Dosage Compensation, Genetic, Drosophila, Transcription, Genetic, Zebrafish, Arabidopsis, Models, Animal, Zebrafish Proteins, Mutant Proteins, Mice, Gene Knockdown Techniques, Gene Knockout Techniques
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