The application proposes to establish a Specialized Center of Research (SCOR) in the Molecular Genetics of Hypertension in the University of Iowa Cardiovascular Center. This initiative, which we have been planning for 18 months, brings together a new cadre of investigators including outstanding molecular geneticists (Val Sheffield and Curt Sigmund at Iowa and John Rapp in Ohio); a genetic epidemiologist and biostatistician (Trudy Burns); and hypertension physiologists (Gerald DiBona, John Stokes, Gary Baumbach, Jean Robillard, David Merrill and Allyn Mark) to pursue the three broad goals of the Hypertension Molecular Genetics SCOR program. The strengths of the proposal include: 1) study of three distinctive human populations including nuclear families from the Muscatine population study of obesity and blood pressure; Bedouin families from a homogeneous population in Southern Israel with a high incidence of obesity and hypertension; and a statewide network of women with preeclampsia; 2) a lcading core human molecular genetics laboratory directed by Val Sheffield with capability for high throughput genotyping facilitating genome wide searches; 3) coordinated pursuit of chromosomal quantitative trait loci and physiologic and cellular intermediate phenotypes in rat models of genetically salt-sensitive hypertension; and 4) the use of tissue specific gene expression and knockouts in transgenic mice to test the role of tissue-specific renin-angiotensin systems in hypertension. The investigators in our SCOR, including John Rapp in Ohio, have established active collaborations and intense interaction. In addition, the investigators in our SCOR have also established extensive collaborations with other investigators in the genetics of hypertension. This coalition of leading molecular geneticists and hypertension physiologists in the Iowa SCOR holds promise for a substantial contribution to advancing knowledge of the molecular genetics of hypertension.
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