Human Longevity Inc., San Diego, California 92121, USA.
J. Craig Venter Institute, Capricorn Lane, La Jolla, California 92037, USA.
Nat Rev Genet. 2018 Jan;19(1):51-62. doi: 10.1038/nrg.2017.75. Epub 2017 Oct 30.
A gene can be defined as essential when loss of its function compromises viability of the individual (for example, embryonic lethality) or results in profound loss of fitness. At the population level, identification of essential genes is accomplished by observing intolerance to loss-of-function variants. Several computational methods are available to score gene essentiality, and recent progress has been made in defining essentiality in the non-coding genome. Haploinsufficiency is emerging as a critical aspect of gene essentiality: approximately 3,000 human genes cannot tolerate loss of one of the two alleles. Genes identified as essential in human cell lines or knockout mice may be distinct from those in living humans. Reconciling these discrepancies in how we evaluate gene essentiality has applications in clinical genetics and may offer insights for drug development.
当一个基因的功能丧失会危及个体的生存能力（例如胚胎致死）或导致适应性严重丧失时，就可以将其定义为必需基因。在群体水平上，可以通过观察对功能丧失变异的耐受性来确定必需基因。有几种计算方法可用于评分基因的必需性，并且在非编码基因组中定义必需性方面取得了一些进展。单倍不足正在成为基因必需性的一个关键方面：大约 3000 个人类基因不能容忍两个等位基因中的一个丢失。在人类细胞系或 knockout 小鼠中被鉴定为必需的基因可能与活人体内的基因不同。协调我们评估基因必需性的这些差异在临床遗传学中有应用，并且可能为药物开发提供见解。
