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(Hypertension. 2007;50:891.)
© 2007 American Heart Association, Inc.

Original Articles

Congenic Interval Mapping of RNO10 Reveals a Complex Cluster of Closely-Linked Genetic Determinants of Blood Pressure

Yasser Saad; Shane Yerga-Woolwine; Jagannath Saikumar; Phyllis Farms; Ezhilarasi Manickavasagam; Edward J. Toland; Bina Joe

From the Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3035 Arlington Ave, Ohio.

Correspondence to Bina Joe, PhD, Physiological Genomics Laboratory, Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3035 Arlington Avenue, Toledo, Ohio 43614-5804. E-mail bina.joe{at}utoledo.edu

Genetic dissection of the rat genome for identifying alleles that cause abnormalities in blood pressure (BP) resulted in the mapping of a significant number of BP quantitative trait loci (QTLs). In this study we mapped at least one such BP QTL on rat chromosome 10 (RNO10) as being within the introgressed segment of a S.LEW congenic strain S.LEWx12x2x3x8 spanning 1.34 Mb from 70 725 437 bp to 72 063 232 bp. BP of 3 congenic strains that span shorter segments of this region was additionally examined. Results obtained indicate that LEW alleles that comprise a 375-kb introgressed segment of the congenic strain S.LEWx12x2x3x5 (70 725 437 bp to 71 100 513 bp) increase BP. The magnitude of change in BP exhibited by the 2 strains, S.LEWx12x2x3x8 and S.LEWx12x2x3x5, is the net phenotypic effect of the underlying genetic determinants of BP. In this respect, the current data are superior to previous QTL localization of BP QTL1, which was hypothesized based on differential congenic segments. Genetic dissection using these 2 congenic strains as tools is expected to facilitate further dissection of the regions. Meanwhile, differential congenic segments were used to predict and thereby prioritize regions for candidate gene analysis. Using this approach, 2 distinct regions of 401 kb and 409 kb within S.LEWx12x2x3x8 and a 104 kb region within S.LEWx12x2x3x5 were prioritized for further consideration. Because all of these genetic elements are located within a 1.06-Mb region of RNO10, our study has revealed a remarkable insight into a genomic module comprising very closely-linked, opposing genetic determinants of BP.

Key Words: hypertension • gene • linkage