Mapping of Quantitative Trait Loci for Blood Pressure and Cardiac Mass in the Rat by Genome Scanning of Recombinant Inbred Strains

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1995 Oct 1

PMID 7560090

Citations 28

Authors

M Pravenec

D Gauguier

J J Schott

J Buard

V Kren

V Bila

C Szpirer

J Szpirer

J M Wang

H Huang

Affiliations

Soon will be listed here.

Abstract

In the HXB and BXH recombinant inbred strains derived from the spontaneously hypertensive rat and the normotensive Brown Norway rat, we determined the strain distribution patterns of 500 genetic markers to scan the rodent genome for quantitative trait loci regulating cardiac mass and blood pressure. The markers spanned approximately 1,139 cM of the genome and were tested for correlations with left ventricular mass adjusted for body weight, and with systolic, diastolic, and mean arterial pressures. The marker for the dopamine 1A receptor (Drd1a) on chromosome 17 showed the strongest correlation with left ventricular heart weight (P = .00038, r = -0.59) and the relationship to heart weight was independent of blood pressure. The markers showing the strongest correlations with systolic, diastolic, and mean arterial pressure were D19Mit7 on chromosome 19 (P = .0012, r = .55), D2N35 on chromosome 2 (P = .0008, r = .56), and Il6 on chromosome 4 (P = .0018, r = .53), respectively. These studies demonstrate that the HXB and BXH strains can be effectively used for genome scanning studies of complex traits and have revealed several chromosome regions that may be involved in the genetic control of blood pressure and cardiac mass in the rat.

Citing Articles

Establishing the hybrid rat diversity program: a resource for dissecting complex traits.

Dwinell M, Takizawa A, Tutaj M, Malloy L, Schilling R, Endsley A Mamm Genome. 2025; 36(1):25-37.

PMID: 39907792 PMC: 11880076. DOI: 10.1007/s00335-024-10102-y.

Research on Experimental Hypertension in Prague (1966-2009).

Kunes J, Zicha J Physiol Res. 2024; 73(Suppl 1):S49-S66.

PMID: 39016152 PMC: 11412355. DOI: 10.33549/physiolres.935425.

Systems Genetics Approaches in Rat Identify Novel Genes and Gene Networks Associated With Cardiac Conduction.

Adriaens M, Lodder E, Moreno-Moral A, Silhavy J, Heinig M, Glinge C J Am Heart Assoc. 2019; 7(21):e009243.

PMID: 30608189 PMC: 6404199. DOI: 10.1161/JAHA.118.009243.

Genomic approaches for the elucidation of genes and gene networks underlying cardiovascular traits.

Adriaens M, Bezzina C Biophys Rev. 2018; 10(4):1053-1060.

PMID: 29934864 PMC: 6082306. DOI: 10.1007/s12551-018-0435-2.

Towards Precision Medicine for Hypertension: A Review of Genomic, Epigenomic, and Microbiomic Effects on Blood Pressure in Experimental Rat Models and Humans.

Padmanabhan S, Joe B Physiol Rev. 2017; 97(4):1469-1528.

PMID: 28931564 PMC: 6347103. DOI: 10.1152/physrev.00035.2016.

References

Pravenec M, Klir P, Kren V, Zicha J, Kunes J . An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains. J Hypertens. 1989; 7(3):217-21. View

Bender K, Seibert R, Wienker T, Kren V, Pravenec M, Bissbort S . Biochemical genetics of methylglyoxal dehydrogenases in the laboratory rat (Rattus norvegicus). Biochem Genet. 1994; 32(5-6):147-54. DOI: 10.1007/BF00554618. View

Vergnaud G . Polymers of random short oligonucleotides detect polymorphic loci in the human genome. Nucleic Acids Res. 1989; 17(19):7623-30. PMC: 334871. DOI: 10.1093/nar/17.19.7623. View

Pravenec M, Kren V, Bila V, Kabra P, Krsiakova M, Simonet L . HXB and BXH sets of recombinant inbred strains: strain distribution patterns of some genetic markers. Transplant Proc. 1990; 22(6):2557-8. View

Kren V . Genetics of the polydactyly-luxate syndrome in the Norway rat, Rattus norvegicus. Acta Univ Carol Med Monogr. 1975; (68):1-103. View

Tanase H, Yamori Y, Hansen C, Lovenberg W . Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats. Hypertension. 1982; 4(6):864-72. DOI: 10.1161/01.hyp.4.6.864. View

Jeffreys A, Wilson V, Kelly R, Taylor B, Bulfield G . Mouse DNA 'fingerprints': analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains. Nucleic Acids Res. 1987; 15(7):2823-36. PMC: 340701. DOI: 10.1093/nar/15.7.2823. View

Lander E, Botstein D . Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics. 1989; 121(1):185-99. PMC: 1203601. DOI: 10.1093/genetics/121.1.185. View

Pravenec M, Kren V, Kunes J, Scicli A, Carretero O, Simonet L . Cosegregation of blood pressure with a kallikrein gene family polymorphism. Hypertension. 1991; 17(2):242-6. DOI: 10.1161/01.hyp.17.2.242. View

10.

Kunes J, Kren V, Klir P, Zicha J, Pravenec M . Genetic determination of heart and kidney weights studied using a set of recombinant inbred strains: the relationship to blood pressure. J Hypertens. 1990; 8(12):1091-5. DOI: 10.1097/00004872-199012000-00004. View

11.

Vergnaud G, Mariat D, Zoroastro M, Lauthier V . Detection of single and multiple polymorphic loci by synthetic tandem repeats of short oligonucleotides. Electrophoresis. 1991; 12(2-3):134-40. DOI: 10.1002/elps.1150120207. View

12.

Plomin R, McClearn G, Gora-Maslak G, Neiderhiser J . Use of recombinant inbred strains to detect quantitative trait loci associated with behavior. Behav Genet. 1991; 21(2):99-116. DOI: 10.1007/BF01066330. View

13.

Neumann P, Collins R . Genetic dissection of susceptibility to audiogenic seizures in inbred mice. Proc Natl Acad Sci U S A. 1991; 88(12):5408-12. PMC: 51882. DOI: 10.1073/pnas.88.12.5408. View

14.

Vergnaud G, Mariat D, Apiou F, Aurias A, Lathrop M, Lauthier V . The use of synthetic tandem repeats to isolate new VNTR loci: cloning of a human hypermutable sequence. Genomics. 1991; 11(1):135-44. DOI: 10.1016/0888-7543(91)90110-z. View

15.

Gora-Maslak G, McClearn G, Crabbe J, Phillips T, Belknap J, Plomin R . Use of recombinant inbred strains to identify quantitative trait loci in psychopharmacology. Psychopharmacology (Berl). 1991; 104(4):413-24. DOI: 10.1007/BF02245643. View

16.

Mariat D, Vergnaud G . Detection of polymorphic loci in complex genomes with synthetic tandem repeats. Genomics. 1992; 12(3):454-8. DOI: 10.1016/0888-7543(92)90434-t. View

17.

Hamet P, Kong D, Pravenec M, Kunes J, Kren V, Klir P . Restriction fragment length polymorphism of hsp70 gene, localized in the RT1 complex, is associated with hypertension in spontaneously hypertensive rats. Hypertension. 1992; 19(6 Pt 2):611-4. DOI: 10.1161/01.hyp.19.6.611.a. View

18.

Serikawa T, Kuramoto T, Hilbert P, Mori M, Yamada J, Dubay C . Rat gene mapping using PCR-analyzed microsatellites. Genetics. 1992; 131(3):701-21. PMC: 1205041. DOI: 10.1093/genetics/131.3.701. View

19.

Jeunemaitre X, Soubrier F, Kotelevtsev Y, Lifton R, Williams C, Charru A . Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992; 71(1):169-80. DOI: 10.1016/0092-8674(92)90275-h. View

20.

Kobayashi E, Tachibana M, Ikadai H, Imamichi T, Kunieda T . Linkage among esterase-6 (Es-6), neural cell adhesion molecule (NCAM), and apolipoprotein C-III (apoc-3) genes on rat chromosome 8. Mamm Genome. 1992; 3(11):656-8. DOI: 10.1007/BF00352485. View