RGD Reference Report - Modularization and epistatic hierarchy determine homeostatic actions of multiple blood pressure quantitative trait loci. - Rat Genome Database

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Modularization and epistatic hierarchy determine homeostatic actions of multiple blood pressure quantitative trait loci.

Authors: Chauvet, C  Crespo, K  Menard, A  Roy, J  Deng, AY 
Citation: Chauvet C, etal., Hum Mol Genet. 2013 Nov 15;22(22):4451-9. doi: 10.1093/hmg/ddt294. Epub 2013 Jun 28.
RGD ID: 7421500
Pubmed: (View Article at PubMed) PMID:23814039
DOI: Full-text: DOI:10.1093/hmg/ddt294

Hypertension, the most frequently diagnosed clinical condition world-wide, predisposes individuals to morbidity and mortality, yet its underlying pathological etiologies are poorly understood. So far, a large number of quantitative trait loci (QTLs) have been identified in both humans and animal models, but how they function together in determining overall blood pressure (BP) in physiological settings is unknown. Here, we systematically and comprehensively performed pair-wise comparisons of individual QTLs to create a global picture of their functionality in an inbred rat model. Rather than each of numerous QTLs contributing to infinitesimal BP increments, a modularized pattern arises: two epistatic 'blocks' constitute basic functional 'units' for nearly all QTLs, designated as epistatic module 1 (EM1) and EM2. This modularization dictates the magnitude and scope of BP effects. Any EM1 member can contribute to BP additively to that of EM2, but not to those of the same module. Members of each EM display epistatic hierarchy, which seems to reflect a related functional pathway. Rat homologues of 11 human BP QTLs belong to either EM1 or EM2. Unique insights emerge into the novel genetic mechanism and hierarchy determining BP in the Dahl salt-sensitive SS/Jr (DSS) rat model that implicate a portion of human QTLs. Elucidating the pathways underlying EM1 and EM2 may reveal the genetic regulation of BP.



Disease Annotations    
hypertension  (IAGP)
Hypotension  (IAGP)

Phenotype Annotations    

Mammalian Phenotype

Phenotype Values via PhenoMiner     Click to see Annotation Detail View
Options:  View chart  |  Download data table  |  View expanded data table  |  Show All Strains Clinical Measurement

Strains with Phenominer Data Strains with phenominer dataStrains with phenominer data
SS.LEW-(D10Chm10-D10Rat11)/Ayd SS.LEW-(D16Chm48-D16Chm60)/Ayd SS.MNS-(D2Rat155-D2Chm419)/Ayd
SS.LEW-(D8Rat56-D8Rat51)/Ayd SS.LEW-(D8Chm14-D8Rat16)/Ayd SS.LEW-(D3Rat52-D3Rat130)/Ayd
SS.LEW-(D17Chm131-D17Chm93)/Ayd SS.LEW-(D17Rat84-D17Chm17)/Ayd SS.LEW-(D2Rat199-D2Mco17)/Ayd
SS.LEW-(D18Chm41-D18Rat92)/Ayd SS SS.LEW-(D5Mit5-D5M4Mit14)/Ayd
SS.LEW-(Prlr-D2Rat143)/Ayd SS.MNS-(D2Mit6-D2Rat303)/Ayd SS.MNS-(D2Got93-D2Rat222)/Ayd
SS.MNS-(D2Chm25-Fgg)/Ayd SS.MNS-(D2Wox27-Adh1)/Ayd SS.MNS-(D2Chm254-D2Chm161)/Ayd
SS.LEW-(D17Chm14-D17Rat65)/Ayd SS.LEW-(D10Chm246-D10Chm257)/Ayd SS.LEW-(D3Rat61-D3Wox1)/Ayd
SS.LEW-(D10Rat194-D10Chm243)/Ayd SS.LEW-(D1Uia4-D1Rat320)/Ayd SS.LEW-(D1Rat320-D1Mgh32)/Ayd
SS.LEW-(D1Chm64-D1Rat19)/Ayd SS.LEW-(D10Chm155-D10Rat127)/Ayd SS.MNS-(D2Rat183-D2Chm113)/Ayd
SS.MNS-(D2Chm161-D2Chm410)/Ayd SS.MNS-(D2Chm366-D2Rat52)/Ayd SS.LEW-(D10Mco30-D10Got107)/Ayd
SS.LEW-(D10Rat24-Igfbp4)/Ayd SS.MNS-(D2Chm90-D2Rat38)/Ayd SS.LEW-(D10Rat27-Igfbp4)/Ayd
SS.LEW-(D7Rat73-D7Rat128)/Ayd SS.LEW-(D17Chm85-D17Chm71)/Ayd SS.LEW-(D10Rat119-D10Rat133)/Ayd
SS.LEW-(D10Rat55-D10Rat13)/Ayd SS.LEW-(D18Chm90-D18Chm4)/Ayd SS.LEW-(D18Wox7-D18Rat67)/Ayd
SS.LEW-(D18Rat55-D18Mgh2)/Ayd SS.LEW-(D18Chm59-D18Rat1)/Ayd SS.LEW-(D3Rat52-D3Chm63)/Ayd
SS.LEW-(D3Chm64-D3Rat17)/Ayd SS.LEW-(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd SS.LEW-(D10Chm10-D10Rat11)(D10Chm246-D10Chm257)/Ayd
SS.LEW-(D10Rat194-D10Chm243)(D16Chm48-D16Chm60)/Ayd SS.LEW-(D10Chm10-D10Rat11)(D16Chm48-D16Chm60)/Ayd SS.LEW-(D8Rat58-D8Chm12)(D10Chm10-D10Rat11)/Ayd
SS.LEW-(D8Rat58-D8Chm12)(D10Rat194-D10Chm243)/Ayd SS.LEW-(D8Chm12-D8Rat15)(D10Rat194-D10Chm243)/Ayd SS.LEW-(D3Rat2-D3Chm79)(D10Rat194-D10Chm243)/Ayd
SS.LEW-(D3Rat2-D3Chm79)(D10Chm10-D10Rat11)/Ayd SS.LEW-(D17Chm131-D17Chm93)(D10Chm10-D10Rat11)/Ayd SS.LEW-(D17Chm131-D17Chm93)(D17Rat84-D17Chm17)/Ayd
SS.LEW-(D2Uia5-D2Mit6)(D10Chm10-D10Rat11)/Ayd SS.LEW-(D2Uia5-D2Mit6)(D10Rat194-D10Chm243)/Ayd SS.LEW-(D16Chm48-D16Chm60)(D18Rat101-D18Rat92)/Ayd
SS.LEW-(D2Uia5-D2Mit6)(D3Rat17-D3Mco80)/Ayd SS.LEW-(D1Uia4-D1Rat320)(D10Chm10-D10Rat11)/Ayd SS.LEW-(D1Rat320-D1Mgh32)(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd
SS.LEW-(D1Chm64-D1Rat19)(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd SS.LEW-(D7Uia3-D7Mgh1)(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd SS.MNS-(D2Chm90-D2Rat38),LEW-(D10Chm10-D10Rat11)/Ayd
SS.MNS-(D2Chm90-D2Rat38),LEW-(D10Got112-Igfbp4)/Ayd SS.MNS-(D2Rat155-D2Chm419),LEW-(D10Rat194-D10Chm243)/Ayd SS.MNS-(D2Rat155-D2Chm419),LEW-(D10Chm10-D10Rat11)/Ayd
SS.MNS-(D2Chm33-Tm2sf1),LEW-(D10Rat194-D10Chm243),LEW-(D10Chm10-D10Rat11)/Ayd SS.MNS-(D2Chm33-Tm2sf1),LEW-(D10Chm10-D10Rat11)/Ayd SS.MNS-(D2Chm33-Tm2sf1),LEW-(D10Rat194-D10Chm243)/Ayd
SS.MNS-(D2Chm33-Tm2sf1),LEW-(D3Rat2-D3Chm79)/Ayd

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
QTL Bp270 Blood pressure QTL 270 Rattus norvegicus
QTL Bp279 Blood pressure QTL 279 Rattus norvegicus
QTL Bp310 Blood pressure QTL 310 Rattus norvegicus
QTL Bp312 Blood pressure QTL 312 Rattus norvegicus
QTL Bp315 Blood pressure QTL 315 Rattus norvegicus
QTL Bp318 Blood pressure QTL 318 Rattus norvegicus
QTL Bp345 Blood pressure QTL 345 Rattus norvegicus
QTL Bp346 Blood pressure QTL 346 Rattus norvegicus
QTL Bp347 Blood pressure QTL 347 Rattus norvegicus
QTL Bp363 Blood pressure QTL 363 Rattus norvegicus
QTL Bp364 Blood pressure QTL 364 Rattus norvegicus
QTL Bp365 Blood pressure QTL 365 Rattus norvegicus
QTL Bp366 Blood pressure QTL 366 Rattus norvegicus
QTL Bp367 Blood pressure QTL 367 Rattus norvegicus
QTL Bp368 Blood pressure QTL 368 Rattus norvegicus
QTL Bp38 Blood pressure QTL 38 Rattus norvegicus
Strain SS.LEW-(D10Chm10-D10Rat11)(D10Chm246-D10Chm257)/Ayd null Rattus norvegicus
Strain SS.LEW-(D10Chm10-D10Rat11)(D16Chm48-D16Chm60)/Ayd null Rattus norvegicus
Strain SS.LEW-(D10Chm155-D10Rat127)/Ayd null Rattus norvegicus
Strain SS.LEW-(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D10Rat194-D10Chm243)(D16Chm48-D16Chm60)/Ayd null Rattus norvegicus
Strain SS.LEW-(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.LEW-(D16Chm48-D16Chm60)(D18Rat101-D18Rat92)/Ayd null Rattus norvegicus
Strain SS.LEW-(D17Chm131-D17Chm93)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D17Chm131-D17Chm93)(D17Rat84-D17Chm17)/Ayd null Rattus norvegicus
Strain SS.LEW-(D18Chm41-D18Rat92)/Ayd null Rattus norvegicus
Strain SS.LEW-(D18Chm59-D18Rat1)/Ayd null Rattus norvegicus
Strain SS.LEW-(D18Chm90-D18Chm4)/Ayd null Rattus norvegicus
Strain SS.LEW-(D18Rat55-D18Mgh2)/Ayd null Rattus norvegicus
Strain SS.LEW-(D18Wox7-D18Rat67)/Ayd null Rattus norvegicus
Strain SS.LEW-(D1Chm64-D1Rat19)(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D1Rat320-D1Mgh32)(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D1Uia4-D1Rat320)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D2Uia5-D2Mit6)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D2Uia5-D2Mit6)(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.LEW-(D3Rat17-D3Mco80)(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.LEW-(D3Rat2-D3Chm79)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D3Rat2-D3Chm79)(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.LEW-(D7Uia3-D7Mgh1)(D10Rat194-D10Chm243)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D8Chm12-D8Rat15)(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.LEW-(D8Rat58-D8Chm12)(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.LEW-(D8Rat58-D8Chm12)(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm161-D2Chm410)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm25-D2Rat131)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm33-Tm2sf1),LEW-(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm33-Tm2sf1),LEW-(D10Rat194-D10Chm243),LEW-(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm33-Tm2sf1),LEW-(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm33-Tm2sf1),LEW-(D3Rat2-D3Chm79)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm90-D2Rat38),LEW-(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm90-D2Rat38),LEW-(D10Got112-Igfbp4)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Chm90-D2Rat38)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Rat155-D2Chm419),LEW-(D10Chm10-D10Rat11)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Rat155-D2Chm419),LEW-(D10Rat194-D10Chm243)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Rat155-D2Chm419)/Ayd null Rattus norvegicus
Strain SS.MNS-(D2Rat183-D2Chm113)/Ayd null Rattus norvegicus

Additional Information