This is a competitive renewal application for continuation of the Hypertension SCOR Grant 5P50 HL55001. The new proposal consists of four scientific projects and two supporting core units. Project I, a continuation of the ongoing clinical project, will expand our collection of hypertensive families, including subjects who have undergone extensive clinical evaluation and can be subgrouped into intermediate phenotypes, as well as families from genetically isolated populations from Greece, Israel and South Africa. Various subsets of our population will be submitted to different genetic analyses as appropriate, including linkage and association studies, genome-wide scan for genetic isolates, evaluation of single nucleotide polymorphisms in selected genes, testing of QTL by microsatellite markers and mapping of promising narrow regions by DNA sequencing Project II, also a continuation of the same project in the current SCOR, will identify and marrow down new and previously described QTL in hypertensive or salt-sensitive mice, targeting regions from which information can be applied to study of homologous human regions. Project II, also a mouse genome project, will further build on analysis of QTL mapping data from inbred mouse crosses of project II and will apply novel statistical methods for QTL mapping data from inbred mouse crosses of Project II and will apply novel statistical methods for the design and analysis of gene expression microarray experiments that may then be applied to analysis of human DNA samples. Project IV, a continuation of the same projects in the current SCOR, will study cellular and molecular mechanisms by which neurohormonal factors cause atherogenesis and cardiac injury both in vitro, using selected cell cultures, and in vivo, using genetically engineered animals. An injury both in vitro, using selected cell cultures, and in vivo, using genetically engineered animals. An Animal Core and an Administrative Core unit will facilitate and coordinate these projects. It is anticipated that crossing information from human and murine genetic studies will help identify genetic contributors to certain types of hypertension or its complications.
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