Chromosomal mapping of quantitative trait loci (QTL) contributing to stroke in a rat model of complex human disease.
What causes the stroke? Is it entirely due to mechanical end organ damage, or is there any hidden genetic basis as it is increasingly the case for most other diseases? Sperenza and collages from Brigham and Women's Hospital in Boston carried out an experiment to understand genetic basis of stroke and identify genes related.
Two inbred mice strains; stroke-prone spontaneously hypertensive rat (SHRsp) and stroke-resistant spontaneously hypertensive rat (SHRsr); were crossed and the hybrid progeny were subjected to a total genome scan.
Three QTLs were identified on different chromosomes, which contributed to 28% of genetic variation associated with stroke. They were named as STR1, STR 2 and STR3; where the first locus accounts for 17% of overall variance. Human and mouse genetic maps of the relevant QTL regions were compared to that of rat, in order to identify any possible candidate genes for above mentioned loci. STR1 and STR 3 showed no colocalisation, but STR 2 showed similarities to human atrial natriuretic factor gene, which is located immediately adjacent to the brain natriuretic factor gene. Both these genes could be candidate genes of the QTL loci, showing major influence on vascular conditions, hence contributing to stroke.
This study is not only significant in demonstrating the strength of using correct animal models to study complex traits, but also in challenging the common concept that stroke is basically attributed to mechanical end-organ damage due to long-term hypertension.
References.
Rubattu S, Volpe M, Kreutz R, Ganten U, Ganten D, and Lindpaintner K. (1996) Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of human disease. Nat Genet 13: 429–434.
