The application of genomics to medicine has accelerated the discovery of mutations underlying disease and has enhanced our knowledge of the molecular underpinnings of diverse pathologies. As the amount of human genetic material queried via sequencing has grown exponentially in recent years, so too has the number of rare variants observed. Despite progress, our ability to distinguish which rare variants have clinical significance remains limited. Over the last decade, however, powerful experimental approaches have emerged to characterize variant effects orders of magnitude faster than before. Fueled by improved DNA synthesis and sequencing and, more recently, by CRISPR/Cas9 genome editing, multiplex functional assays provide a means of generating variant effect data in wide-ranging experimental systems. Here, I review recent applications of multiplex assays that link human variants to disease phenotypes and I describe emerging strategies that will enhance their clinical utility in coming years.

中文翻译：

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将基因组变异与疾病联系起来：测试人类突变功能影响的可扩展方法

基因组学在医学上的应用加速了疾病突变的发现，并增强了我们对多种病理学分子基础的了解。近年来，随着通过测序查询的人类遗传物质的数量呈指数级增长，观察到的罕见变异的数量也呈指数级增长。尽管取得了进展，但我们区分哪些罕见变异具有临床意义的能力仍然有限。然而，在过去的十年中，出现了强大的实验方法，能够比以前更快地表征变异效应。在改进的 DNA 合成和测序以及最近的 CRISPR/Cas9 基因组编辑的推动下，多重功能测定提供了一种在广泛的实验系统中生成变异效应数据的方法。在这里，我回顾了将人类变异与疾病表型联系起来的多重检测的最新应用，并描述了将在未来几年增强其临床实用性的新兴策略。