蛋白截断变异（protein-truncating variant，PTV）

蛋白截断变异（protein-truncating variant，PTV）通过引入终止密码子，移码突变或剪接位点，破坏蛋白编码基因[1]。蛋白截断变异的研究对于人类进化（human evolution），基因功能（gene function），疾病相关变异（disease-related variants）和疾病患者变异的临床解读（Clinical interpretation of variants in patients with disease）有着重要作用[2-7]。由于蛋白截断变异普遍为罕见突变，大规模人群的研究十分有必要。过万的样本量才适合有统计学功效（power）的蛋白截断变异研究。目前最大的蛋白截断研究来源于Broad研究所Daniel MacArthur教授的6万人ExAC人类外显子组整合数据库（ExAC Exome Aggregation Consortium）[2]。

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5. Bartha, I., di Iulio, J., Venter, J. C. & Telenti, A. Human gene essentiality. Nat. Rev. Genet. 19, 51–62 (2018).
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