(Hypertension. 2000;35:179.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Applicability of a "Speed" Congenic Strategy to Dissect Blood Pressure Quantitative Trait Loci on Rat Chromosome 2
From the Department of Medicine and Therapeutics (B.J., C.D.N., D.G., J.S.C., N.H.A., A.F.D.), University of Glasgow, Western Infirmary, Glasgow, UK; and The Wellcome Trust Centre for Human Genetics (D.G.), Oxford, UK.
Correspondence to Prof Anna F. Dominiczak, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK. E-mail anna.dominiczak{at}clinmed.gla.ac.uk
Abstract—The identification of any quantitative trait locus (QTL) via a genome scan is only the first step toward the ultimate goal of gene identification. The next step is the production of congenic strains by which the existence of a QTL may be verified and the implicated chromosomal region be reduced to a size applicable to positional cloning of the causal gene. We used a speed congenic breeding protocol previously verified in mice for 2 blood pressure QTLs on rat chromosome 2. Four congenic strains were produced through introgression of various segments of chromosome 2 from Wistar-Kyoto rats from Glasgow colonies [WKY(Gla) rats] into the recipient stroke-prone spontaneously hypertensive rats from Glasgow colonies [SHRSP(Gla)], and vice versa. The number of backcross generations required for each strain to achieve complete homozygosity at 83 background genetic markers in a "best" male varied between 3 and 4. Transfer of the region of rat chromosome 2 containing both QTLs from WKY(Gla) into an SHRSP(Gla) genetic background lowered both baseline and salt-loaded systolic blood pressure by 
20 and 40 mm Hg in male congenic rats compared with the SHRSP parental strain (F=53.4, P<0.005; F=28.0, P< 0.0005, respectively). In contrast, control animals for stowaway heterozygosity presented no deviation from the blood pressure values recorded for the SHRSP(Gla), indicating that if such heterozygosity exists, its effect on blood pressure is negligible. A reciprocal strategy in which 1 or both QTLs on rat chromosome 2 were transferred from SHRSP(Gla) into a WKY(Gla) genetic background resulted in statistically significant but smaller blood pressure increases for 1 of these QTLs. These results confirm the existence of blood pressure QTLs on rat chromosome 2 and demonstrate the applicability of a speed congenic strategy in the rat and emphasize the important role of the genetic background.
Key Words: hypertension, genetic • genes • rats, inbred strokeprone SHR
This article has been cited by other articles:
 |
|
 |
|
  D. Graham, N. N. Huynh, C. A. Hamilton, E. Beattie, R. A.J. Smith, H. M. Cocheme, M. P. Murphy, and A. F. Dominiczak Mitochondria-Targeted Antioxidant MitoQ10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy Hypertension, August 1, 2009; 54(2): 322 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Graham, M. W. McBride, M. Gaasenbeek, K. Gilday, E. Beattie, W. H. Miller, J. D. McClure, J. M. Polke, A. Montezano, R. M. Touyz, et al. Candidate Genes That Determine Response to Salt in the Stroke-Prone Spontaneously Hypertensive Rat: Congenic Analysis Hypertension, December 1, 2007; 50(6): 1134 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Munroe, C. Wallace, M.-Z. Xue, A. C. B. Marcano, R. J. Dobson, A. K. Onipinla, B. Burke, J. Gungadoo, S. J. Newhouse, J. Pembroke, et al. Increased Support for Linkage of a Novel Locus on Chromosome 5q13 for Essential Hypertension in the British Genetics of Hypertension Study Hypertension, July 1, 2006; 48(1): 105 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Mullins, M. A. Bailey, and J. J. Mullins Hypertension, Kidney, and Transgenics: A Fresh Perspective Physiol Rev, April 1, 2006; 86(2): 709 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Charron, R. Lambert, V. Eliopoulos, C. Duong, A. Menard, J. Roy, and A. Y. Deng A loss of genome buffering capacity of Dahl salt-sensitive model to modulate blood pressure as a cause of hypertension Hum. Mol. Genet., December 15, 2005; 14(24): 3877 - 3884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Eliopoulos, J. Dutil, Y. Deng, M. Grondin, and A. Y. Deng Severe hypertension caused by alleles from normotensive Lewis for a quantitative trait locus on chromosome 2 Physiol Genomics, June 16, 2005; 22(1): 70 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dutil, V. Eliopoulos, E.-L. Marchand, A. M. Devlin, J. Tremblay, K. Prithiviraj, P. Hamet, A. Migneault, D. deBlois, and A. Y. Deng A quantitative trait locus for aortic smooth muscle cell number acting independently of blood pressure: implicating the angiotensin receptor AT1B gene as a candidate Physiol Genomics, May 11, 2005; 21(3): 362 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. McBride, M. J. Brosnan, J. Mathers, L. I. McLellan, W. H. Miller, D. Graham, N. Hanlon, C. A. Hamilton, J. M. Polke, W. K. Lee, et al. Reduction of Gstm1 Expression in the Stroke-Prone Spontaneously Hypertension Rat Contributes to Increased Oxidative Stress Hypertension, April 1, 2005; 45(4): 786 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Dominiczak, D. Graham, M. W. McBride, N. J.R. Brain, W. K. Lee, F. J. Charchar, M. Tomaszewski, C. Delles, and C. A. Hamilton Cardiovascular Genomics and Oxidative Stress Hypertension, April 1, 2005; 45(4): 636 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dutil, V. Eliopoulos, J. Tremblay, P. Hamet, S. Charron, and A. Y. Deng Multiple Quantitative Trait Loci for Blood Pressure Interacting Epistatically and Additively on Dahl Rat Chromosome 2 Hypertension, April 1, 2005; 45(4): 557 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grondin, V. Eliopoulos, R. Lambert, Y. Deng, A. Ariyarajah, M. Moujahidine, J. Dutil, S. Charron, and A. Y. Deng Complete and overlapping congenics proving the existence of a quantitative trait locus for blood pressure on Dahl rat chromosome 17 Physiol Genomics, March 21, 2005; 21(1): 112 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kaneko, V. L. M. Herrera, T. Didishvili, and N. Ruiz-Opazo Sex-specific effects of dual ET-1/ANG II receptor (Dear) variants in Dahl salt-sensitive/resistant hypertension rat model Physiol Genomics, January 20, 2005; 20(2): 157 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Cowley Jr, R. J. Roman, and H. J. Jacob Application of chromosomal substitution techniques in gene-function discovery J. Physiol., January 1, 2004; 554(1): 46 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. McBride, F. J. Charchar, D. Graham, W. H. Miller, P. Strahorn, F. J. Carr, and A. F. Dominiczak Functional genomics in rodent models of hypertension J. Physiol., January 1, 2004; 554(1): 56 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Palijan, J. Dutil, and A. Y. Deng Quantitative trait loci with opposing blood pressure effects demonstrating epistasis on Dahl rat chromosome 3 Physiol Genomics, September 29, 2003; 15(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. McBride, F. J. Carr, D. Graham, N. H. Anderson, J. S. Clark, W. K. Lee, F. J. Charchar, M. J. Brosnan, and A. F. Dominiczak Microarray Analysis of Rat Chromosome 2 Congenic Strains Hypertension, March 1, 2003; 41(3): 847 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Alemayehu, L. Breen, D. Krenova, and M. P. Printz Reciprocal rat chromosome 2 congenic strains reveal contrasting blood pressure and heart rate QTL Physiol Genomics, September 3, 2002; 10(3): 199 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. DUTIL and A. Y. DENG Further chromosomal mapping of a blood pressure QTL in Dahl rats on chromosome 2 using congenic strains Physiol Genomics, June 6, 2001; 6(1): 3 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Negrin, M. W. McBride, H. V. O. Carswell, D. Graham, F. J. Carr, J. S. Clark, B. Jeffs, N. H. Anderson, I. M. Macrae, and A. F. Dominiczak Reciprocal Consomic Strains to Evaluate Y Chromosome Effects Hypertension, February 1, 2001; 37(2): 391 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Dominiczak, D. C. Negrin, J. S. Clark, M. J. Brosnan, M. W. McBride, and M. Y. Alexander Genes and Hypertension : From Gene Mapping in Experimental Models to Vascular Gene Transfer Strategies Hypertension, January 1, 2000; 35(1): 164 - 172. [Abstract] [Full Text] [PDF]
|
|