RGD Reference Report - Refined mapping of the renal failure RF-3 quantitative trait locus. - Rat Genome Database

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Refined mapping of the renal failure RF-3 quantitative trait locus.

Authors: O'Meara, CC  Lazar, J  Hoffman, M  Moreno, C  Jacob, HJ 
Citation: O'Meara CC, etal., J Am Soc Nephrol. 2011 Mar;22(3):518-25. Epub 2010 Dec 2.
RGD ID: 5684423
Pubmed: PMID:21127141   (View Abstract at PubMed)
PMCID: PMC3060445   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2010060661   (Journal Full-text)

Rf-3, a quantitative trait locus (QTL) on rat chromosome 3, affects the development of CKD in Fawn-Hooded Hypertensive (FHH) rats. This QTL spans 110 Mb and approximately 1400 genes; therefore, narrowing the position of this locus is necessary to elucidate potential candidate genes. Here, we used congenic models and comparative genomics to refine the Rf-3 candidate region. We generated congenic lines carrying smaller intervals (subcongenics) of the Rf-3 region and used these lines to reduce the Rf-3 candidate region by 94% (to 7.1 Mb). We used comparative genomics to identify QTL for both nephropathy and albuminuria in the syntenic region of this interval for both human and mouse. We also used the overlapping homologous regions to reduce the number of likely positional candidate genes to 13 known or predicted genes. By combining congenic models and cross-species studies, we narrowed the list of candidate genes to a level that we could sequence the whole interval to further identify the causative gene in future studies.

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Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ACI.FHH-(D1Mit18-D1Rat90)(D3Got102-D3Got149)(D14Mit11-D14Rat33)(D14Rat65-D14Rat90)/McwiRatincreased mean systemic arterial blood pressure inducedIAGPright nephrectomycompared to ACI.FHH-D1Mit18-D1Rat90D14Mit11-D14Rat33D14Rat65-D14Rat90/EurMcwi and ACI.FHH-D1Mit18-D1Rat90D3Rat6-D3Got149D14Mit11-D14Rat33D14Rat65-D14Rat90/McwiRGD 
Rf59Ratincreased urine protein level  IDA  RGD 
ACI.FHH-(D1Mit18-D1Rat90)(D3Got102-D3Got149)(D14Mit11-D14Rat33)(D14Rat65-D14Rat90)/McwiRatrenal cast inducedIAGPright nephrectomy RGD 

Objects referenced in this article
QTL Albq5_m albuminuria QTL 5 (mouse) Mus musculus
Strain ACI.FHH-(D1Mit18-D1Rat90)(D14Mit11-D14Rat33)(D14Rat65-D14Rat90)/EurMcwi null Rattus norvegicus
Strain ACI.FHH-(D1Mit18-D1Rat90)(D3Rat6-D3Got149)(D14Mit11-D14Rat33)(D14Rat65-D14Rat90)/Mcwi null Rattus norvegicus

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