癌细胞中的遗传交互网络。
Genetic interaction networks in cancer cells.
机构信息
Donnelly Centre, University of Toronto, ON, Canada.
Donnelly Centre, University of Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, ON, Canada.
出版信息
Curr Opin Genet Dev. 2019 Feb;54:64-72. doi: 10.1016/j.gde.2019.03.002. Epub 2019 Apr 8.
The genotype-to-phenotype relationship in health and disease is complex and influenced by both an individual's environment and their unique genome. Personal genetic variants can modulate gene function to generate a phenotype either through a single gene effect or through genetic interactions involving two or more genes. The relevance of genetic interactions to disease phenotypes has been particularly clear in cancer research, where an extreme genetic interaction, synthetic lethality, has been exploited as a therapeutic strategy. The obvious benefits of unmasking genetic background-specific vulnerabilities, coupled with the power of systematic genome editing, have fueled efforts to translate genetic interaction mapping from model organisms to human cells. Here, we review recent developments in genetic interaction mapping, with a focus on CRISPR-based genome editing technologies and cancer.
基因型与表型在健康和疾病中的关系是复杂的，受到个体环境和独特基因组的影响。个体遗传变异可以通过单个基因效应或涉及两个或多个基因的遗传相互作用来调节基因功能，从而产生表型。遗传相互作用与疾病表型的相关性在癌症研究中尤为明显，其中一种极端的遗传相互作用，即合成致死性，已被用作一种治疗策略。揭示遗传背景特异性脆弱性的明显好处，加上系统基因组编辑的强大功能，促使人们努力将遗传相互作用图谱从模式生物转化为人类细胞。在这里，我们回顾了遗传相互作用图谱的最新进展，重点介绍了基于 CRISPR 的基因组编辑技术和癌症。
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