183 The Sa gene locus cosegregates with increased blood pressure in the spontaneously hypertensive rat

Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.

“…Although studies in segregating populations derived from the SHR have been useful for the tentative identification of multiple autosomes that may contain genes regulating blood pressure (e.g., chromosomes 1, 2, 4, 8, 10, 13, 16, 19, and 20), considerable uncertainty exists regarding the actual contribution of any of these chromosomes in the pathogenesis of spontaneous hypertension (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In the current studies, we have developed a novel congenic strain of SHR in which we have genetically isolated a region of chromosome 8 that plays a major role in the pathogenesis of spontaneous hypertension in the SHR-BN model.…”

“…Although this strain has been the subject of extensive physiologic and biochemical investigation, little is known about the primary genetic lesions responsible for the pathogenesis of spontaneous hypertension. Recent linkage studies in recombinant inbred strains and in F2 populations derived from the SHR and normotensive strains have suggested that BP quantitative trait loci (QTLs) may exist on chromosomes 1, 2, 4, 8, 10, 13, 16, 19, and 20 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, the individual contributions of each of these chromosomes in the pathogenesis of spontaneous hypertension have not been clearly defined.…”

Genetic mapping of two blood pressure quantitative trait loci on rat chromosome 1.

“…The SA gene has been linked to markers on rat chromosome 1 (6,7). Alleles at the SA locus were shown to cosegregate with blood pressure in F 2 populations derived from an SHR ϫ WKY cross (8,9), a stroke prone-SHR ϫ WKY cross (6), and an F 2 population derived from an S ϫ Lewis cross (10). The SA locus in humans was linked to blood pressure in a Japanese population (11) but not in a European population (12).…”

A pharmacogenetic approach to blood pressure in Lyon hypertensive rats. A chromosome 2 locus influences the response to a calcium antagonist.

“…Recent studies have shown that dissection of complex quantitative traits such as blood pressure (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) or glucose homeostasis (22, 25) regulation into subphenotypes may provide important tools in the resolution of genetic heterogeneity of conditions such as hypertension and non-insulin-dependent diabetes mellitus. In this study, dissection of blood pressure into additional subphenotypes using a pharmacological approach has been useful in identifying a QTL which may be specifically involved in calcium metabolism-related blood pressure regulation.…”

“…Recently, molecular genetics, using either the candidate gene approach or random genome scanning, has allowed several loci that influence blood pressure to be identified in rat models of genetic hypertension (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In addition, experimental strategies have led to the identification of loci that may specifically influence the blood pressure response to salt (3,4,7,8,11,12), the temporal change in blood pressure (14), individual hemodynamic components of blood pressure (5), and the risk of end-organ damage (13).…”