scholarly journals Localization of a blood pressure QTL on rat chromosome 1 using Dahl rat congenic strains

1999 ◽  
Vol 1 (3) ◽  
pp. 119-125 ◽  
Author(s):  
YASSER SAAD ◽  
MICHAEL R. GARRETT ◽  
SOON JIN LEE ◽  
HOWARD DENE ◽  
JOHN P. RAPP
Keyword(s):  
Blood Pressure ◽  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Congenic Strain ◽  
Chromosome 1 ◽  
Congenic Strains ◽  
Salt Hypertension ◽  
Trait Locus

Saad, Yasser, Michael R. Garrett, Soon Jin Lee, Howard Dene, and John P. Rapp. Localization of a blood pressure QTL on rat chromosome 1 using Dahl rat congenic strains. Physiol. Genomics 1: 119–125, 1999.—We previously reported that markers on rat chromosome 1 are genetically linked to blood pressure in an F2 population derived from Dahl salt hypertension-sensitive (S) and Lewis (LEW) rats. Because there was evidence for more than one blood pressure quantitative trait locus (QTL) on chromosome 1, an initial congenic strain introgressing a large 118-centimorgan (cM) segment of LEW chromosome 1 into the S background had been constructed. This initial congenic strain had a reduced blood pressure compared with S rats, proving the existence of a blood pressure QTL, but not giving a good localization of the QTL. In the present work a series of five overlapping congenic substrains were produced from the original congenic strain in order to localize a blood pressure QTL to a 25-cM region near the center of chromosome 1. The congenic substrains also ruled out the Sa locus as a blood pressure QTL in the S vs. LEW comparison because the Sa locus was contained in a congenic substrain that did not alter blood pressure.

Complete and overlapping congenics proving the existence of a quantitative trait locus for blood pressure on Dahl rat chromosome 17

2005 ◽  
Vol 21 (1) ◽  
pp. 112-116 ◽  
Author(s):  
Myrian Grondin ◽  
Vasiliki Eliopoulos ◽  
Raphaelle Lambert ◽  
Yishu Deng ◽  
Anita Ariyarajah ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Congenic Strain ◽  
Chromosome 17 ◽  
Congenic Strains ◽  
Genome Wide ◽  
A Genome ◽  
Trait Locus ◽  
Negative Controls

Linkage studies suggested that a quantitative trait locus (QTL) for blood pressure (BP) was present in a region on chromosome 17 (Chr 17) of Dahl salt-sensitive (DSS) rats. A subsequent congenic strain targeting this QTL, however, could not confirm it. These conflicting results called into question the validity of localization of a QTL by linkage followed by the use of a congenic strain made with an incomplete chromosome coverage. To resolve this issue, we constructed five new congenic strains, designated C17S.L1 to C17S.L5, that completely spanned the ±2 LOD confidence interval supposedly containing the QTL. Each congenic strain was made by replacing a segment of the DSS rat by that of the normotensive Lewis (LEW) rat. The only section to be LL homozygous is the region on Chr 17 specified in a congenic strain, as evidenced by a total genome scan. The results showed that BPs of C17S.L1 and C17S.L2 were lower ( P < 0.04) than that of DSS rats. In contrast, BPs of C17S.L3, C17S.L4, and C17S.L5 were not different ( P > 0.6) from that of DSS rats. Consequently, a BP QTL must be located in an interval of ∼15 cM shared between C17S.L1 and C17S.L2 and unique to them both, as opposed to C17S.L3, C17S.L4, and C17S.L5. The present study illustrates the importance of thorough chromosome coverage, the necessity for a genome-wide screening, and the use of “negative” controls in physically mapping a QTL by congenic strains.

scholarly journals Defining a rat blood pressure quantitative trait locus to a <81.8 kb congenic segment: comprehensive sequencing and renal transcriptome analysis

2010 ◽  
Vol 42A (2) ◽  
pp. 153-161 ◽  
Author(s):  
K. Gopalakrishnan ◽  
J. Saikumar ◽  
C. G. Peters ◽  
S. Kumarasamy ◽  
P. Farms ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Quantitative Trait Locus ◽  
Transcriptome Analysis ◽  
Quantitative Trait ◽  
Congenic Strain ◽  
Association Studies ◽  
Chromosome 9 ◽  
Genome Wide Association Studies ◽  
Congenic Strains ◽  
Trait Locus

Evidence from multiple linkage and genome-wide association studies suggest that human chromosome 2 (HSA2) contains alleles that influence blood pressure (BP). Homologous to a large segment of HSA2 is rat chromosome 9 (RNO9), to which a BP quantitative trait locus (QTL) was previously mapped. The objective of the current study was to further resolve this BP QTL. Eleven congenic strains with introgressed segments spanning <81.8 kb to <1.33 Mb were developed by introgressing genomic segments of RNO9 from the Dahl salt-resistant (R) rat onto the genome of the Dahl salt-sensitive (S) rat and tested for BP. The congenic strain with the shortest introgressed segment spanning <81.8 kb significantly lowered BP of the hypertensive S rat by 25 mmHg and significantly increased its mean survival by 45 days. In contrast, two other congenic strains had increased BP compared with the S. We focused on the <81.8 kb congenic strain, which represents the shortest genomic segment to which a BP QTL has been mapped to date in any species. Sequencing of this entire region in both S and R rats detected 563 variants. The region did not contain any known or predicted rat protein coding genes. Furthermore, a whole genome renal transcriptome analysis between S and the <81.8 kb S.R congenic strain revealed alterations in several critical genes implicated in renal homeostasis. Taken together, our results provide the basis for future studies to examine the relationship between the candidate variants within the QTL region and the renal differentially expressed genes as potential causal mechanisms for BP regulation.

scholarly journals Successful Isolation of a Rat Chromosome 1 Blood Pressure Quantitative Trait Locus in Reciprocal Congenic Strains

Hypertension ◽  
1998 ◽  
Vol 32 (4) ◽  
pp. 639-646 ◽  
Author(s):  
Simon A. Frantz ◽  
Michael Kaiser ◽  
Sheila M. Gardiner ◽  
Dominique Gauguier ◽  
Madeleine Vincent ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Chromosome 1 ◽  
Congenic Strains ◽  
Successful Isolation ◽  
Trait Locus

Replacement of α1-Na-K-ATPase of Dahl rats by Milan rats lowers blood pressure but does not affect its activity

2001 ◽  
Vol 7 (2) ◽  
pp. 171-177 ◽  
Author(s):  
SERGEI N. ORLOV ◽  
JULIE DUTIL ◽  
PAVEL HAMET ◽  
ALAN Y. DENG
Keyword(s):  
Blood Pressure ◽  
Quantitative Trait Locus ◽  
Atpase Activity ◽  
Quantitative Trait ◽  
Chromosome Region ◽  
Homologous Region ◽  
Congenic Strains ◽  
Baseline Activity ◽  
Trait Locus

Both linkage and use of congenic strains have shown that a chromosome region near the gene for the Na-K-ATPase α1-subunit ( Atp1a1) contained a quantitative trait locus (QTL) for blood pressure (BP). Currently, two congenic strains, designated S.M5 and S.M6, were made by replacing a segment of the Dahl salt-sensitive SS/Jr (S) rat by the homologous region of the Milan normotensive rat (MNS). In S.M5, the gene for Atp1a1 is from the MNS strain; whereas in S.M6, Atp1a1 is from the S strain. The baseline activity of the α1-Na-K-ATPase and its stoichiometry were evaluated by an assay of ouabain-sensitive inwardly and outwardly directed 86Rb and 22Na fluxes in erythrocytes. The two congenic strains showed a similar BP, but both had a BP lower than that of S rats ( P < 0.0001). Neither the α1-Na-K-ATPase activity nor its stoichiometry was affected by the substitution of the Atp1a1 alleles of S by those of MNS. Thus the BP-lowering effects observed in S.M5 and S.M6 could not be attributed to the α1-Na-K-ATPase activity or its stoichiometry. Atp1a1 is not supported as a candidate to be a BP QTL.

Two closely linked interactive blood pressure QTL on rat chromosome 5 defined using congenic Dahl rats

2002 ◽  
Vol 8 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Michael R. Garrett ◽  
John P. Rapp
Keyword(s):  
Blood Pressure ◽  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Congenic Strain ◽  
Major Effect ◽  
Large Region ◽  
Chromosome 5 ◽  
Low Blood Pressure ◽  
Trait Locus

Previously we reported the construction of a congenic strain, S.LEW( 5 ), spanning a large region of rat chromosome 5. The Lewis (LEW) strain was the donor, and the Dahl salt-sensitive (S) strain was the recipient. The congenic strain included a blood pressure quantitative trait locus (QTL). In the present work, a series of nine congenic substrains were constructed from S.LEW( 5 ) which defined two closely linked blood pressure QTL in the region previously thought to contain only one. LEW low-blood-pressure alleles at both QTL were required for a major effect on blood pressure. Neither LEW allele alone had a significant effect on blood pressure. The two QTL were localized to regions 6.3 and 4.6 cM, and these were 1.0 cM apart.

scholarly journals Relation of Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 to Hyperactivity of Rostralventrolateral Medulla

Hypertension ◽  
2009 ◽  
Vol 53 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Kamon Iigaya ◽  
Hiroo Kumagai ◽  
Toru Nabika ◽  
Yuji Harada ◽  
Hiroshi Onimaru ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Chromosome 1 ◽  
Trait Locus
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