Abstract

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.

1. Medical Research Council Clinical Sciences Centre and Imperial College London, Du Cane Road, London W12 0NN, UK.
2. University of Missouri, 1600 E. Rollins Road, Columbia, Missouri 65211, USA.
3. The Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
4. University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
5. European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, UK.
6. Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
7. Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
8. University of Wisconsin-Madison, 1400 University Avenue, Madison, Wisconsin 53706, USA.
9. Mayo Clinic, 200 First Street, Rochester, Minnesota 55905, USA.
10. Karolinska Institutet, 17177 Stockholm, Sweden.
11. Max-Delbrück Center for Molecular Medicine, Robert-Rossle-Strasse 10, 13092 Berlin, Germany.
12. Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
13. University of Iowa, 375 Newton Road, Iowa City, Iowa 52242, USA.
14. University of Edinburgh, Edinburgh, Scotland EH16 4TJ, UK.
15. Karolinska Hospital, Karolinska Institutet, 17176 Stockholm, Sweden.
16. Institute of Physiology, Czech Academy of Sciences and Centre for Applied Genomics, Vídeská 1083, 142 20 Prague 4, Czech Republic.
17. Institute of Biology and Medical Genetics, Charles University, Albertov 4, 128 00 Prague 2, Czech Republic.
18. Center for Molecular Genetics and Genomics, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
19. Université libre de Bruxelles, Rue Profs Jeener & Brachet, BE-6041 Gosselies (Charleroi), Belgium.
20. Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA.

Correspondence to: Timothy J Aitman¹ e-mail: t.aitman@csc.mrc.ac.uk

Correspondence to: Howard J Jacob⁷ e-mail: jacob@mcw.edu

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