The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. Genome-wide association studies in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains problematic. In the context of significant progress in rat genomic resources over the past decade, we outline achievements in rat gene discovery to date, show how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms. Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research.
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This Perspective is supported by 257 members of the rat genetics and genomics community, who are listed in Supplementary Table 1 online. The authors thank them for their support in the drafting of the manuscript.
The consomic rats are distributed through Physiogenix, for which H.J.J. is a founder and significant shareholder. The Program for Genomic Application grant required a commercial distributor. When Charles River reneged on distribution, Physiogenix stepped in to fill this need. Physiogenix is formally a contract research organization and contracts with Hilltop Farms to distribute the rats.
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Aitman, T., Critser, J., Cuppen, E. et al. Progress and prospects in rat genetics: a community view. Nat Genet 40, 516–522 (2008). https://doi.org/10.1038/ng.147
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