CHROMOSOMAL MAPPING OF QUANTITATIVE TRAIT LOCI CONTRIBUTING TO STROKEIN A RAT MODEL OF COMPLEX HUMAN-DISEASE

Stroke is a complex disorder with a poorly understood multifactorial a nd polygenic aetiology. We used the stroke-prone spontaneously hyperte nsive rat (SHRSP) as a model organism, mated it with the stroke-resist ant spontaneously hypertensive rat (SHR) and performed a genome-wide s creen in the resultant F2 cohort where latency until stroke, but not h ypertension (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 natriureti c factor, peptides with important vasoactive properties. Our results d emonstrate the existence of primary, blood pressure-independent geneti c factors predisposing to a complex form of stroke.