蛋白截斷變異（protein-truncating variant，PTV）通過引入終止密碼子，移碼突變或剪接位點，破壞蛋白編碼基因[1]。蛋白截斷變異的研究對於人類進化（human evolution），基因功能（gene function），疾病相關變異（disease-related variants）和疾病患者變異的臨床解讀（Clinical interpretation of variants in patients with disease）有着重要作用[2-7]。由於蛋白截斷變異普遍為罕見突變，大規模人群的研究十分有必要。過萬的樣本量才適合有統計學功效（power）的蛋白截斷變異研究。目前最大的蛋白截斷研究來源於Broad研究所Daniel MacArthur教授的6萬人ExAC人類外顯子組整合數據庫（ExAC Exome Aggregation Consortium）[2]。
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- 6. Ganna, A., Satterstrom, K., Zekavat, S., Das, I., Kurki, M., Churchhouse, C., & Neale, B. (2018). Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum. Am J Hum Genet, 102(6), 1204–1211.
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