Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease.
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.
Rubattu
S
S
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Volpe
M
M
Kreutz
R
R
Ganten
U
U
Ganten
D
D
Lindpaintner
K
K
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