RGD Reference Report - Cardiac pathways distinguish two epistatic modules enacting BP quantitative trait loci and candidate gene analysis. - Rat Genome Database

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Cardiac pathways distinguish two epistatic modules enacting BP quantitative trait loci and candidate gene analysis.

Authors: Chauvet, C  Menard, A  Tremblay, J  Xiao, C  Shi, Y  L'heureux, N  Cardin, S  Tardif, JC  Nattel, S  Deng, AY 
Citation: Chauvet C, etal., Hypertens Res. 2009 Jul;32(7):631-7. doi: 10.1038/hr.2009.70. Epub 2009 May 22.
RGD ID: 7421631
Pubmed: PMID:19461651   (View Abstract at PubMed)
DOI: DOI:10.1038/hr.2009.70   (Journal Full-text)

Animal models emulating essential hypertension are an informative means by which to elucidate the physiological mechanisms and gene-gene interactions underlying blood pressure (BP) regulation. We have localized earlier quantitative trait loci (QTLs) for BP on Chromosome (Chr) 2 of Dahl salt-sensitive (DSS) rats, but their chromosome delineations were too large for gene identification. To advance toward positional cloning of these QTLs, we constructed congenic strains that systematically dissect a Chr 2 segment with no overlaps. BP and cardiac functions were measured by telemetry and echocardiography. Six QTLs were delimited, each independently influencing BP. The intervals lodging two of them harbor 10-15 genes and undefined loci. These six QTLs can be grouped into two epistatic modules distinguishable by cardiac pathways/cascades. None of the genes known to exert physiological effects on BP in the segments harboring the six QTLs are leading candidates, as their protein products are the same in DSS rats and similar to those in their Milan normotensive counterparts. Specifically, the lack of an amino-acid alteration, coupled with a lack of difference in the alpha1-Na-K-ATPase activity, excluded ATPase, Na+/K+-transporting, alpha-1 polypeptide as a candidate gene for C2QTL6. The identification of the six QTLs will likely develop into a novel diagnostic and/or therapeutic target for essential hypertension and hypertension-associated diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diastolic Dysfunction inducedIAGPcontrolled sodium content diet7421631; 7421631compared to C2S.M21RGD 
Hypotension  IAGP 7421631; 7421631; 7421631; 7421631; 7421631; 7421631as compared to parental SS/JrRGD 
Hypotension MODEL: inducedIAGPcontrolled sodium content diet7421631; 7421631; 7421631; 7421631; 7421631compared to parental SS/JrRGD 
Hypotension MODEL: controlIAGPcontrolled sodium content diet7421631compared to congenicsRGD 

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Objects Annotated

QTLs
Bp363  (Blood pressure QTL 363)
Bp364  (Blood pressure QTL 364)
Bp365  (Blood pressure QTL 365)
Bp366  (Blood pressure QTL 366)
Bp367  (Blood pressure QTL 367)
Bp368  (Blood pressure QTL 368)

Objects referenced in this article
QTL Bp256 Blood pressure QTL 256 Rattus norvegicus
QTL Bp257 Blood pressure QTL 257 Rattus norvegicus
QTL Bp258 Blood pressure QTL 258 Rattus norvegicus
Strain SS.MNS-(D2Chm442-D2Chm410)/Ayd null Rattus norvegicus

Additional Information