RGD Reference Report - Defining a rat blood pressure quantitative trait locus to a <81.8 kb congenic segment: comprehensive sequencing and renal transcriptome analysis. - Rat Genome Database

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

Authors: Gopalakrishnan, K  Saikumar, J  Peters, CG  Kumarasamy, S  Farms, P  Yerga-Woolwine, S  Toland, EJ  Schnackel, W  Giovannucci, DR  Joe, B 
Citation: Gopalakrishnan K, etal., Physiol Genomics. 2010 Sep;42A(2):153-61. Epub 2010 Aug 17.
RGD ID: 4889902
Pubmed: PMID:20716646   (View Abstract at PubMed)
PMCID: PMC2957796   (View Article at PubMed Central)
DOI: DOI:10.1152/physiolgenomics.00122.2010   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SS.SR-(D9Mco98-Resp18)/1McoRathypertension inducedIAGPcontrolled sodium content diet RGD 
SS.SR-(D9Mco98-Resp18)/2McoRathypertension inducedIAGPcontrolled sodium content diet RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SS.SR-(D9Mco95-D9Mco98)/McoRatdecreased heart weight inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco95-D9Mco98)/McoRatdecreased mean systemic arterial blood pressure inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco95-D9Mco98)/McoRatdecreased pulse pressure inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco95-D9Mco98)/McoRatdecreased systemic arterial diastolic blood pressure inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco95-D9Mco98)/McoRatdecreased systemic arterial systolic blood pressure inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco95-D9Mco98)/McoRatextended life span inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco98-Resp18)/1McoRatincreased systemic arterial systolic blood pressure inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco98-Resp18)/2McoRatincreased systemic arterial systolic blood pressure inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
SS.SR-(D9Mco101-Resp18)/McoRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.SR-(D9Mco14-Resp18)/1McoRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.SR-(D9Mco14-Resp18)/2McoRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.SR-(D9Mco95-D9Mco100)/1McoRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.SR-(D9Mco95-D9Mco102)/McoRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.SR-(D9Mco98-Resp18)/1McoRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.SR-(D9Mco98-Resp18)/2McoRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content dietcompared to SS/JrRGD 
Objects referenced in this article
Marker D9Mco95 D9Mco95 Rattus norvegicus
Marker D9Mco96 D9Mco96 Rattus norvegicus
Marker D9Mco97 D9Mco97 Rattus norvegicus
Marker D9Mco98 D9Mco98 Rattus norvegicus
Marker D9Mco99 D9Mco99 Rattus norvegicus
Marker D9Mco100 D9Mco100 Rattus norvegicus
Marker D9Mco101 D9Mco101 Rattus norvegicus
Marker D9Mco102 D9Mco102 Rattus norvegicus
Strain SS.SR-(D9Mco14-Resp18)/3Mco null Rattus norvegicus
Strain SS.SR-(D9Mco72-Resp18)/Mco null Rattus norvegicus
Strain SS.SR-(D9Mco95-D9Mco100)/2Mco null Rattus norvegicus
Strain SS.SR-(D9Rat89-Resp18)/Mco null Rattus norvegicus

Additional Information