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 ◽  
...  
1999 ◽  
Vol 1 (3) ◽  
pp. 119-125 ◽  
Author(s):  
YASSER SAAD ◽  
MICHAEL R. GARRETT ◽  
SOON JIN LEE ◽  
HOWARD DENE ◽  
JOHN P. RAPP

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.


Hypertension ◽  
1997 ◽  
Vol 30 (2) ◽  
pp. 199-202 ◽  
Author(s):  
Alan Y. Deng ◽  
Howard Dene ◽  
John P. Rapp

2001 ◽  
Vol 7 (2) ◽  
pp. 171-177 ◽  
Author(s):  
SERGEI N. ORLOV ◽  
JULIE DUTIL ◽  
PAVEL HAMET ◽  
ALAN Y. DENG

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.


2005 ◽  
Vol 21 (1) ◽  
pp. 112-116 ◽  
Author(s):  
Myrian Grondin ◽  
Vasiliki Eliopoulos ◽  
Raphaelle Lambert ◽  
Yishu Deng ◽  
Anita Ariyarajah ◽  
...  

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.


Hypertension ◽  
2009 ◽  
Vol 53 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Kamon Iigaya ◽  
Hiroo Kumagai ◽  
Toru Nabika ◽  
Yuji Harada ◽  
Hiroshi Onimaru ◽  
...  

2003 ◽  
Vol 21 (11) ◽  
pp. 2077-2084 ◽  
Author(s):  
Bina Joe ◽  
Michael R Garrett ◽  
Howard Dene ◽  
John P Rapp

Hypertension ◽  
1999 ◽  
Vol 34 (4) ◽  
pp. 643-648 ◽  
Author(s):  
Norbert Hübner ◽  
Young-Ae Lee ◽  
Klaus Lindpaintner ◽  
Detlev Ganten ◽  
Reinhold Kreutz

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