Chung Brian Hon Yin, Chau Jeffrey Fong Ting, Wong Gane Ka-Shu
Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Department of Medicine and Department of Biological Sciences, The University of Alberta, Edmonton, AB, Canada.
NPJ Genom Med. 2021 Feb 24;6(1):19. doi: 10.1038/s41525-021-00176-x.
Precision medicine initiatives are being launched worldwide, each with the capacity to sequence many thousands to millions of human genomes. At the strategic planning level, all are debating the extent to which these resources will be directed towards rare diseases (and cancers) versus common diseases. However, these are not mutually exclusive choices. The organizational and governmental infrastructure created for rare diseases is extensible to common diseases. As we will explain, the underlying technology can also be used to identify drug targets for common diseases with a strategy focused on naturally occurring human knockouts. This flips on its head the prevailing modus operandi of studying people with diseases of interest, shifting the onus to defining traits worth emulating by pharmaceuticals, and searching phenotypically for people with these traits. This also shifts the question of what is rare or common from the many underlying causes to the possibility of a common final pathway.
全球正在开展精准医学计划，每个计划都有能力对成千上万乃至数百万个人类基因组进行测序。在战略规划层面，各方都在讨论这些资源将在多大程度上用于罕见病（和癌症）而非常见疾病。然而，这些并非相互排斥的选择。为罕见病建立的组织和政府基础设施可扩展至常见疾病。正如我们将解释的那样，基础技术还可用于通过聚焦自然发生的人类基因敲除的策略来识别常见疾病的药物靶点。这彻底颠覆了研究患有所关注疾病人群的主流运作方式，将责任转移到定义值得制药公司效仿的特征，并从表型上寻找具有这些特征的人。这也将罕见或常见的问题从众多潜在病因转移到共同最终途径的可能性上。
