Objectif Recent genetic studies have identified hundreds of susceptibility genes for common human diseases but genetic effects are small and identifying underlying mechanisms remains challenging. Rodent models offer significant advantages for analysis of disease phenotypes. Advances in genome resources and gene targeting have increased the attractiveness of the rat model for genetic studies but progress has been hampered by absence of relevant rat genome sequences.We recently sequenced the genome of the spontaneously hypertensive rat (SHR) and will shortly have completed the Wistar Kyoto (WKY) rat sequence. The SHR genome contains over 750 genes that are completely or partly deleted, or have a frameshift in their open reading frame. These sequence variants, along with variants controlling dysregulated gene expression that we characterised previously, most likely include the major determinants of SHR cardiovascular and metabolic disease phenotypes.We shall determine the functional consequences of these variants by creating and phenotyping transgenic and knockout rats on the SHR and WKY genetic backgrounds, using transposon-mediated transgenesis and zinc-finger nuclease-mediated gene deletion recently shown to be highly efficient in rats. Genes will be prioritised for study by statistical and informatic analyses using our extensive physiological, gene expression and linkage data in these rat strains, and by comparative analysis with data from human genome-wide association studies. Confirmed rat disease genes will be tested for conserved functions in humans.These proposals provide a systematic route to elucidating the molecular and functional basis of disease phenotypes in SHR and WKY rats, and for translating these findings to advance understanding of common human diseases. Champ scientifique natural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS2 - ERC Advanced Grant - Genetics, Genomics, Bioinformatics and Systems Biology Appel à propositions ERC-2010-AdG_20100317 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil THE UNIVERSITY OF EDINBURGH Contribution de l’UE € 1 253 482,71 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Royaume-Uni Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Chercheur principal Timothy Aitman (Prof.) Contact administratif Alan Kennedy (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire THE UNIVERSITY OF EDINBURGH Royaume-Uni Contribution de l’UE € 1 253 482,71 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Chercheur principal Timothy Aitman (Prof.) Contact administratif Alan Kennedy (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Participation terminée Royaume-Uni Contribution de l’UE € 1 222 625,51 Adresse SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Voir sur la carte Région London Inner London — West Westminster Type d’activité Higher or Secondary Education Establishments Contact administratif Scott Wheatley (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée