INFRAFRONTIER GmbH, Neuherberg / Munich, Bavaria, 85764, Germany.
F1000Res. 2021 Jun 8;10:456. doi: 10.12688/f1000research.25369.1. eCollection 2021.
In the last few decades, forward genetics approaches have been extensively used to identify gene function. Essentially, forward genetics is the elucidation of the genetic basis of a specific phenotype by screening a population containing random genomic modifications that alter gene function. These approaches have shed light on some essential gene functions in development and disease and have expanded the realm of understanding for genetic disorders. Due to the availability of efficient mutagenesis methods, phenotyping techniques, reliable validation, comprehensive sequence information and translational potential, mouse models are favored for forward genetics approaches. However, in this post-genomic CRISPR-Cas9 era, the relevance and future of forward genetics was brought into question. With more than 7300 mouse strains archived and close interactions with several leading mouse researchers around the world, INFRAFRONTIER - the European Research Infrastructure for mouse models organised a panel discussion on forward genetics at the International Mammalian Genome Conference 2018 to discuss the future of forward genetics as well as challenges faced by researchers using this approach in the current research environment. The commentary presents an overview of this discussion.
在过去的几十年中,正向遗传学方法已被广泛用于鉴定基因功能。从本质上讲,正向遗传学是通过筛选包含改变基因功能的随机基因组修饰的群体,阐明特定表型的遗传基础。这些方法揭示了一些在发育和疾病中至关重要的基因功能,并扩展了对遗传疾病的理解领域。由于高效的诱变方法、表型分析技术、可靠的验证、全面的序列信息和转化潜力,因此,小鼠模型成为正向遗传学方法的首选。然而,在这个后基因组 CRISPR-Cas9 时代,正向遗传学的相关性和未来受到了质疑。INFRAFRONTIER - 欧洲小鼠模型研究基础设施,拥有 7300 多种已存档的小鼠品系,并与世界各地的几位领先的小鼠研究人员密切合作,在 2018 年国际哺乳动物基因组会议上组织了一个关于正向遗传学的小组讨论,以讨论在当前研究环境中使用这种方法的研究人员所面临的挑战以及正向遗传学的未来。评论概述了这次讨论。