Kontarakis Z Stainier DYR 2020 Genetics has recently benefited from the genome engineering revolution: genes can be knocked out, knocked down, or activated more easily than ever before. This range of genetic manipulations has also provided a range of outcomes, sometimes contradictory. But how much interesting biology hides within these discrepancies? Recent studies have shown that genetic compensation can be activated by some gene perturbations and not others, hinting that this phenomenon might skew our understanding of the genotype-phenotype relationship. We review the main findings regarding transcriptional adaptation, a newly discovered form of genetic compensation, and discuss their possible implications for establishing and analyzing animal and plant models to study gene function. We also touch upon how this new knowledge could benefit our understanding of disease-causing mutations and help explain cases of low penetrance or variable expressivity in human genetics. application/pdf https://sonar.ch/global/documents/199785 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tig.2020.08.008 info:eu-repo/semantics/altIdentifier/pmid/32928563 info:eu-repo/semantics/openAccess Trends in genetics : TIG. - 2020 animal models gene expression genetic compensation genome engineering transcriptional adaptation Genetics in Light of Transcriptional Adaptation. http://purl.org/coar/resource_type/c_6501