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Originally published as Genetics Published Articles Ahead of Print on October 8, 2006.

Genetics, Vol. 174, 2203-2213, December 2006, Copyright © 2006
doi:10.1534/genetics.106.061747

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Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3

Soon Jin Lee, Jun Liu, Allison M. Westcott, Joshua A. Vieth, Sarah J. DeRaedt, Siming Yang, Bina Joe and George T. Cicila1

Department of Physiology, Pharmacology, Metabolism and Cardiovascular Sciences, University of Toledo College of Medicine, Toledo, Ohio 43614

1 Corresponding author: Department of Physiology, Pharmacology, Metabolism and Cardiovascular Sciences, University of Toledo College of Medicine, 3035 Arlington Ave., Block Health Science Bldg., Toledo, OH 43614.
E-mail: george.cicila{at}utoledo.edu

Substitution mapping was used to refine the localization of blood pressure (BP) quantitative trait loci (QTL) within the congenic region of S.R-Edn3 rats located at the q terminus of rat chromosome 3 (RNO3). An F2(S x S.R-Edn3) population (n = 173) was screened to identify rats having crossovers within the congenic region of RNO3 and six congenic substrains were developed that carry shorter segments of R-rat-derived RNO3. Five of the six congenic substrains had significantly lower BP compared to the parental S rat. The lack of BP lowering effect demonstrated by the S.R(ET3 x 5) substrain and the BP lowering effect retained by the S.R(ET3 x 2) substrain together define the RNO3 BP QTL-containing region as ~4.64 Mb. Two nonoverlapping substrains, S.R(ET3 x 1) and S.R(ET3 x 6), had significantly lower BP compared to the S strain, indicating the presence of two distinct BP QTL in the RNO3 q terminus. The RNO3 q terminus was fine mapped with newly developed polymorphic markers to characterize the extent of the congenic regions. The two RNO3 BP QTL regions were thus defined as within intervals of 0.05–1.12 and 0.72–1.25 Mb, respectively. Also important was our difficulty in fine mapping and marker placement in this portion of the rat genome (and thus candidate gene identification) using the available genomic data, including the rat genome sequence.




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[Abstract] [Full Text] [PDF]


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