Human Knockout Carriers: Dead, Diseased, Healthy, or Improved?

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• 作者：Vagheesh M. Narasimhan¹ ; Yali Xue¹ ; Chris Tyler-Smith¹ ; ^{cts@sanger.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：loss-of-function variants ; gene function ; clinical interpretation
• 刊名：Trends in Molecular Medicine
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：22
• 期：4
• 页码：341-351
• 全文大小：1588 K

文摘

Whole-genome and whole-exome sequence data from large numbers of individuals reveal that we all carry many variants predicted to inactivate genes (knockouts). This discovery raises questions about the phenotypic consequences of these knockouts and potentially allows us to study human gene function through the investigation of homozygous loss-of-function carriers. Here, we discuss strategies, recent results, and future prospects for large-scale human knockout studies. We examine their relevance to studying gene function, population genetics, and importantly, the implications for accurate clinical interpretations.