Hypertension is a major cause of cardiovascular diseases, with damage to target organs constituting the principal source of morbidity and mortality. In addition to the health burden, these problems also translate into huge costs for the Medicare budget. There is evidence that damage to target organs does not correlate well with the severity of hypertension, but might rather be explained by susceptibility factors, including genetic ones. Our long-term objectives are to identify genes linked to two important complications of hypertension: (1) left ventricular hypertrophy (L.H.), and (2) hypertension-induced renal damage (HIRD). Since such complex disease manifestations are typically controlled by several genes that have weak effects, it is difficult to detect such genes directly in humans. One alternative is to use animal models of such conditions and, after finding candidate genes, to extrapolate these findings to humans. We will therefore use genetically pure line of rodents that constitute models for L.H. and HIRD, and cross them to the other inbred strains to generate genetic segregating populations. The progeny of these crosses will be extensively phenotyped and genotyped in order identify quantitative trait loci (QTL) linked to either L.H. or HIRD. Subsequently, congenic lines will be generated to: (1) validate the effects of the QTLs, and (2) provide models to perform experiments aimed at identifying candidate mechanisms and candidate genes linked to the trait of interest.
