title: Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease.
abstract: Stroke is a complex disorder with a poorly understood multifactorial and polygenic aetiology. We used the stroke-prone spontaneously hypertensive rat (SHRSP) as a model organism, mated it with the stroke-resistant spontaneously hypertensive rat (SHR) and performed a genome-wide screen in the resultant F2 cohort where latency until stroke, but not hypertension (a major confounder) segregated. We identified three major quantitative trait loci, STR1-3, with lod scores of 7.4, 4.7 and 3.0, respectively, that account for 28% of the overall phenotypic variance. STR2 colocalizes with the genes encoding atrial and brain natriuretic factor, peptides with important vasoactive properties. Our results demonstrate the existence of primary, blood pressure-independent genetic factors predisposing to a complex form of stroke.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rubattu
authors.forename: M
authors.initials: M
authors.lastname: Volpe
authors.forename: R
authors.initials: R
authors.lastname: Kreutz
authors.forename: U
authors.initials: U
authors.lastname: Ganten
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: K
authors.initials: K
authors.lastname: Lindpaintner
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002561:Cerebrovascular Disorders / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D004195:Disease Models, Animal; D008040:Genetic Linkage; D006801:Humans; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR