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Rat Genome Mapping and Genomics

par Szpirer, Claude ;Levan, Göran
Editeur scientifique Denny, Paul;Kole, Chittaranjan
Référence Genome Mapping and Genomics in Laboratory Animals, Springer, Heidelberg, page (217-256)
Publication Publié, 2012

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Résumé :

The rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and common diseases. Unlike the mouse, the rat was neglected by geneticists. However, most traits and diseases studied in the rat are complex, polygenic, and their analysis requires genetic approaches. Rat genome mapping and genomics were considerably developed in the last two decades, starting, as in the human, with chromosome and cytogenetic mapping based on standard somatic cell hybrids and fluorescence in situ hybridization (FISH). Linkage and radiation hybrid maps were then constructed that included genes, expressed sequences tags (EST), and microsatellite markers and they were integrated with the cytogenetic map. The genome sequences of two rat strains were published in 2004 (BN) and 2010 (spontaneous hypertensive rat, SHR), and thousands of various DNA polymorphisms have been identified. The availability of these resources has stimulated numerous linkage studies in rat crosses and in recombinant inbred strains, leading to the genetic identification of hundreds of quantitative trait loci (QTLs) influencing various traits and demonstrating that the rat is a valuable experimental model, including for geneticists. In addition, high-throughput gene expression profiling and genetical genomics have been applied to the rat, adding a new dimension to disease gene discovery. Several rat genes have now been identified that underlie complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes and also suggesting new therapeutic approaches. A major biological limitation of the rat as a model was the lack of totipotent embryonic stem (ES) cells; this limitation was recently removed and targeted knockout rats can now be generated. It can reasonably be predicted that identification of numerous relevant disease genes will be achieved in rat models in a near future and that these results will help in understanding the mechanisms underlying common human diseases, thereby also stimulating the development of new therapies. © 2012 Springer-Verlag Berlin Heidelberg.