Genome-Wide Identification of Allelic Expression in Hypertensive Rats

Background— Identification of genes involved in complex cardiovascular disease traits has proven challenging. Inbred animal models can facilitate genetic studies of disease traits. The spontaneously hypertensive rat (SHR) is an inbred model of hypertension that exists in several closely related but genetically distinct lines. Methods and Results— We used renal gene-expression profiling across 3 distinct SHR lines to identify genes that show different expression in SHR than in the genetically related normotensive control strain, Wistar-Kyoto. To ensure robust discovery of genes showing SHR-specific expression differences, we considered only those genes in which differential expression is replicated in multiple animals of each of multiple hypertensive rat lines at multiple time points during the ontogeny of hypertension. Mutation analysis was performed on the identified genes to uncover allelic variation. We identified those genes in which all SHR lines share a single allele of the gene when normotensive co...