title: Multiple blood pressure loci with opposing blood pressure effects on rat chromosome 1 in a homologous region linked to hypertension on human chromosome 15.
abstract: Genetic dissection of blood pressure (BP) quantitative trait loci (QTLs) in rats has facilitated the fine-mapping of regions linked to the inheritance of hypertension. The goal of the current study was to further fine-map one such genomic region on rat chromosome 1 (BPQTL1b1), the homologous region of which on human chromosome 15 harbors BP QTLs, as reported by four independent studies. Of the six substrains constructed and studied, the systolic BP of two of the congenic strains were significantly lower by 36 and 27 mm Hg than that of the salt-sensitive (S) rat (P < 0.0001, P = 0.0003, respectively). The congenic segments of these two strains overlapped between 135.12 and 138.78 Mb and contained eight genes and two predicted miRNAs. None of the annotations had variants within expressed sequences. These data taken together with the previous localization resolved QTL1b1 with a 70% improvement from the original 7.39 Mb to the current 2.247 Mb interval. Furthermore, the systolic BP of one of the congenic substrains was significantly higher by 20 mm Hg (P < 0.0001) than the BP of the S rat. The limits of this newly identified QTL with a BP increasing effect (QTL1b1a) were between 134.12 and 135.76 Mb, spanning 1.64 Mb, containing two protein-coding genes, Mctp2 and Rgma, and a predicted miRNA. There were four synonymous variants within Mctp2. These data provide evidence for two independent BP QTLs with opposing BP effects within the previously identified BP QTL1b1 region. Additionally, these findings illustrate the complexity underlying the genetic mechanisms of BP regulation, wherein inherited elements beyond protein-coding sequences or known regulatory regions could be operational.
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
authors.forename: Blair
authors.initials: B
authors.lastname: Mell
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
authors.forename: Shakila
authors.initials: S
authors.lastname: Abdul-Majeed
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
authors.forename: Sivarajan
authors.initials: S
authors.lastname: Kumarasamy
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
authors.forename: Harshal
authors.initials: H
authors.lastname: Waghulde
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
authors.forename: Resmi
authors.initials: R
authors.lastname: Pillai
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, Program in Physiological Genomics, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D040641:Quantitative Trait Loci; D020303:Rats, Inbred Dahl; D011917:Rats, Inbred Lew