Genome Engineering and Measurement Laboratory, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland; Functional Genomics Center Zurich of ETH Zurich/University of Zurich, Zurich, Switzerland..
Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Trends Genet. 2020 Dec;36(12):926-935. doi: 10.1016/j.tig.2020.08.008. Epub 2020 Sep 11.
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.
与以往相比,基因更容易被敲除、敲低或激活。这些基因操作范围提供了一系列结果,有时甚至相互矛盾。但是,这些差异背后隐藏着多少有趣的生物学现象呢?最近的研究表明,遗传补偿可以被一些基因扰动激活,而不能被另一些激活,这暗示着这种现象可能会扭曲我们对基因型-表型关系的理解。我们综述了关于转录适应的主要发现,这是一种新发现的遗传补偿形式,并讨论了它们对建立和分析动物和植物模型以研究基因功能的可能影响。我们还探讨了这一新知识如何有助于我们理解致病突变,并有助于解释人类遗传学中低外显率或可变表达的情况。