Objectif Linkage studies with the spontaneously hypertensive rat (SHR) have revealed several chromosome regions that contain quantitative trait loci (QTLS) with the capacity to affect blood pressure. However, the resolving power of these linkage studies may be limited to the distances on the order of about 20cM. With polygenic disorders like hypertension, one cannot reliably identify recombinants in segregating populations. In addition, it is difficult to detect small changes in population blood pressure that may result from using a marker 10-20cM distant from a true blood pressure locus. To solve these problems, we propose to use congenic strains. Such strains are genetically identical except for a single chromosome segment. In the current application, we propose a production of new congenic strains by transferring chromosome segments from a normotensive Brown-Norway (BN) strain onto the genetic background of the SHR strain. We will transfer chromosome segments containing markers that were proved in segregating populations to contain blood pressure regulatory QTls. Resulting congenic strains will provide definitive evidence that blood pressure QTL exists in the transferred segment. Furthermore, searching for recombinants within the differential segment will help to narrow it to only several cM and to localize the blood pressure regulatory QTL. In addition to the production of congenic strains, we plan to search for blood pressure regulatory QTls in so far not studied regions of the genome of recombinant inbred (RI) strains that were derived from SHR and BN progenitors. At present, these strains were typed in more than 500 markers, several of which were found to be significantly associated with blood pressure. We also propose to obtain additional phenotypes (response to cardiovascular pharmacological probes) and to map responsible QTls with several hundred additional gene markers, available through EURHYPGEN. Co-ordinator's Note: This additional proposal will bring into EURHYPGEN a group with a long-standing interest in the genetics of hypertension. The group were the first to breed recombinant-inbred strains from hypertensive spontaneous hypertension. Their proposed development of congenic strains to localize causative genes will undoubtedly advance and complement the work being done within EURHYPGEN. Programme(s) IC-PECO/COPERNICUS - Scientific and technological cooperation between the European Community and European non-member countries, 1992- Thème(s) 0201 - CEEC participation in BIOMEDICAL AND HEALTH RESEARCH programme Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur University of Leicester Contribution de l’UE Aucune donnée Adresse Leicester Royal Infirmary LE2 7LX Leicester Royaume-Uni Voir sur la carte Coût total Aucune donnée Participants (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire INSTITUTE OF PHYSIOLOGY - CZECH ACADEMY OF SCIENCES Tchéquie Contribution de l’UE Aucune donnée Adresse 1083,Videnska 1083 142 20 PRAHA 4 Voir sur la carte Coût total Aucune donnée
