Gurumurthy Channabasavaiah B, Grati M'hamed, Ohtsuka Masato, Schilit Samantha L P, Quadros Rolen M, Liu Xue Zhong
Developmental Neuroscience, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA.
Mouse Genome Engineering Core Facility, Vice Chancellor for Research Office, University of Nebraska Medical Center, Omaha, NE, USA.
Hum Genet. 2016 Sep;135(9):971-6. doi: 10.1007/s00439-016-1704-4. Epub 2016 Jul 7.
Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the disease. While many technological advances have helped improve these approaches, some gaps still remain. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated), which has emerged as a revolutionary genetic engineering tool, holds great promise for closing such gaps. By combining the benefits of forward and reverse genetics, it has dramatically expedited human genetics research. We provide a perspective on the power of CRISPR-based forward and reverse genetics tools in human genetics and discuss its applications using some disease examples.
人类遗传学研究采用正向遗传学和反向遗传学这两种相反的方法。正向遗传学识别突变并将其与观察到的疾病病因联系起来，而反向遗传学则在模式生物中诱导突变以研究它们在疾病中的作用。在大多数情况下，正向遗传学鉴定出的突变的因果关系通过反向遗传学得到证实，即通过构建基因工程动物模型以及评估该模型是否能够重现疾病。虽然许多技术进步有助于改进这些方法，但仍存在一些差距。CRISPR/Cas（成簇规律间隔短回文重复序列/CRISPR相关蛋白）作为一种革命性的基因工程工具出现，有望填补这些差距。通过结合正向遗传学和反向遗传学的优势，它极大地加速了人类遗传学研究。我们阐述了基于CRISPR的正向和反向遗传学工具在人类遗传学中的强大作用，并通过一些疾病实例讨论了其应用。
