Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2

The identification of any quantitative trait locus (QTL) via a genome scan is only the first step toward the ultimate goal of gene identification. The next step is the production of congenic strains by which the existence of a QTL may be verified and the implicated chromosomal region be reduced to a size applicable to positional cloning of the causal gene. We used a speed congenic breeding protocol previously verified in mice for 2 blood pressure QTLs on rat chromosome 2. Four congenic strains were produced through intr ogression of various segments of chromosome 2 from Wistar-Kyoto rats from G lasgow colonies [WKY(Gla) rats] into the recipient stroke-prone spontaneous ly hypertensive rats from Glasgow colonies [SHRSP(Gla)], and vice versa. Th e number of backcross generations required for each strain to achieve compl ete homozygosity at 83 background genetic markers in a "best" male varied b etween 3 and 4. Transfer of the region of rat chromosome 2 containing both QTLs from WKY(Gla) into an SHRSP(Gla) genetic background lowered both basel ine and salt-loaded systolic blood pressure by approximate to 20 and approx imate to 40 mm Hg in male congenic rats compared with the SHRSP parental st rain (F=53.4, P<0.005; F=28.0, P<0.0005, respectively). In contrast, contro l animals for stowaway heterozygosity presented no deviation from the blood pressure values recorded for the SHRSP(Gla), indicating that if such heter ozygosity exists, its effect on blood pressure is negligible. A reciprocal strategy in which 1 or both QTLs on rat chromosome 2 were transferred from SHRSP(Gla) into a WKY(Gla) genetic background resulted in statistically sig nificant but smaller blood pressure increases for 1 of these QTLs. These re sults confirm the existence of blood pressure QTLs on rat chromosome 1 and demonstrate the applicability of a speed congenic strategy in the rat and e mphasize the important role of the genetic background.