Dissecting the primary causes of genetic hypertension in rats.

Abstract

Blood pressure has a genetic component influenced by several to many genetic loci in both humans and animals; that is, blood pressure is a polygenic trait. Ultimately, the primary causes of genetic hypertension can only be established with genetic techniques. The primary tools for this analysis in animals are inbred strains of rodents selectively bred for differences in blood pressure and the genetic analysis of these strains by cosegregation techniques. This analysis determines whether it is possible to separate specific alleles at a candidate genetic locus from a component of blood pressure in genetically segregating populations. If the candidate alleles cosegregate with a component of blood pressure, these alleles must be the cause of the blood pressure differences or be linked on the same chromosome to alleles at other loci that cause blood pressure differences. If, on the other hand, the candidate alleles do not cosegregate with blood pressure, they cannot be the cause of the blood pressure differences. This analysis is straightforward in the case of a single-locus Mendelian candidate trait but is less informative if a candidate trait is itself polygenic. In this case, genetic analysis yields either 1) results that are compatible with, but not definitive proof for, a genetic role of the trait in causing blood pressure differences or 2) results that eliminate the trait as a cause of genetic differences in blood pressure. A complete listing of all the traits that have undergone genetic cosegregation analysis in rodents is given.