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

Genetic compensation: A phenomenon in search of mechanisms

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

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pgen.1006780

Cites

156 of 156 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Even in a true gene knockout, the time required for a single cell clone to propagate might be sufficient for cells to establish genetic compensation, altering expression patterns of related proteins.

    “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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [3]Muller HJ, editor Further studies on the nature and causes of gene mutations. Proceedings of the 6th International Congress of Genetics; 1932.

Cited by

Sorted by citations

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
Published
2017-07-13
Volume
13
Issue
7
Pages
e1006780
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
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
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

About these checks

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review