Cited by 830Developmental Biology and Gene RegulationRNA Research and SplicingZebrafish Biomedical Research Applications

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Genetic compensation: A phenomenon in search of mechanisms

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El-Brolosy, Mohamed A., Stainier, Didier Y. R.·2017·PLOS Genetics

DOI 10.1371/journal.pgen.1006780PMC PMC5509088

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Abstract

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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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.
ORCID: El-Brolosy, Mohamed A.
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
DOI: 10.1371/journal.pgen.1006780
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: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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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Genetic compensation: A phenomenon in search of mechanisms

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