Quantitative trait loci for body weight, blood pressure, blood glucose, and serum lipids: Linkage analysis with wild rats (Rattus norvegicus)

To study polygenetically inherited human diseases like hypertension, inbred rat strains are usually the preferred models. Because many inbred generati ons under optimized environmental conditions may have led to the survival o f "silent" disease genes, we used a cross between one wild rat and genetica lly hypertensive SHR rats to analyze quantitative trait loci (QTLs) of bloo d pressure and related traits. The (Wild x SHR)F1 hybrids were transferred into a pathogen-free environment by wet-hysterectomy and were backcrossed o nto SHR to generate first backcross hybrids (BC1). Progeny from one F1 fema le (n = 72) were phenotypically and genetically characterized to map QTLs. Significant, subsignificant, and suggestive evidence was found for more sex -specific than common linkage of blood pressure and most blood-pressure-rel ated traits. Male- and female-specific regions were determined on different chromosomes for blood pressures (Chrs. 2 and 7 vs 5 and 11), body weight ( Chrs. 10 vs 18), and blood glucose (Chr. 17 vs 20). A linkage in both males and females was shown for serum triglycerides on chromosomes 6 and 17, res pectively, and blood glucose on chromosome 15. For serum total cholesterol, a significant linkage was found on chromosome 14 only in males. Our findin gs not only indicate the complex character of quantitative traits per se bu t also show impressively their dependence on sex, age, and strains in coseg regation analysis. (C) 2001 Academic Press.