RGD Reference Report - Combined genealogical, mapping, and expression approaches to identify spontaneously hypertensive rat hypertension candidate genes. - Rat Genome Database

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Combined genealogical, mapping, and expression approaches to identify spontaneously hypertensive rat hypertension candidate genes.

Authors: Hinojos, CA  Boerwinkle, E  Fornage, M  Doris, PA 
Citation: Hinojos CA, etal., Hypertension 2005 Apr;45(4):698-704. Epub 2005 Feb 14.
RGD ID: 1357414
Pubmed: PMID:15710778   (View Abstract at PubMed)
DOI: DOI:10.1161/01.HYP.0000156498.78896.37   (Journal Full-text)

Allelic expression in genes has become recognized as a heritable trait by which phenotypes are generated. We have examined gene expression in the rat kidney using genome-wide microarray technology (Affymetrix). Gene expression was determined across 4 rat strains, 3 hypertensive spontaneously hypertensive rat (SHR) substrains (SHR-A3, SHR-B2, and SHR-C), and a normotensive strain (Wistar-Kyoto [WKY]). Expression measurements were made in multiple animals from all strains at 4 time points (4 weeks, 8 weeks, 12 weeks, and 18 weeks of age), covering the prehypertensive period in SHR (4 weeks), and the period of rapidly rising blood pressure (8 and 12 weeks) and of sustained hypertension (18 weeks). Regression analysis revealed a close relationship across all strains during the first 3 time points, after which SHR-A3 became a substantial outlier. SHR-B2 and SHR-C demonstrated a very close relationship in gene expression at all times but also showed increased differences compared with the other strains at 18 weeks of age. We identified genes that were consistently different in expression, comparing all SHR substrains at each time point with WKY. The resulting list of genes was compared with blood pressure quantitative trait loci reported for SHR to refine a number of genes consistently differentially expressed between SHR substrains and WKY, persistently differentially expressed across multiple time points, and located in SHR blood pressure-determinative regions of the genome. Genealogical relationships and SHR substrain intercrosses suggest that genes responsible for heritable hypertension in SHR are shared across SHR substrains. The present approach identifies a number of genes that may influence blood pressure in SHR by virtue of allelic effects on gene expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOPtprj (Rattus norvegicus)1357414; 1357414 RGD 
hypertension  IAGP 1357414 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptprj  (protein tyrosine phosphatase, receptor type, J)

Genes (Mus musculus)
Ptprj  (protein tyrosine phosphatase receptor type J)

Genes (Homo sapiens)
PTPRJ  (protein tyrosine phosphatase receptor type J)

Objects referenced in this article
Gene Afm afamin Rattus norvegicus
Gene Bhmt betaine-homocysteine S-methyltransferase Rattus norvegicus
Gene Cela1 chymotrypsin like elastase 1 Rattus norvegicus
Gene Ddt D-dopachrome tautomerase Rattus norvegicus
Gene Dpep1 dipeptidase 1 Rattus norvegicus
Gene Ephx2 epoxide hydrolase 2 Rattus norvegicus
Gene Gsto1 glutathione S-transferase omega 1 Rattus norvegicus
Gene Gstt2 glutathione S-transferase theta 2 Rattus norvegicus
Gene Hmox2 heme oxygenase 2 Rattus norvegicus
Gene Homer2 homer scaffold protein 2 Rattus norvegicus
Gene Lgals1 galectin 1 Rattus norvegicus
Gene Magi3 membrane associated guanylate kinase, WW and PDZ domain containing 3 Rattus norvegicus
Gene Mat2a methionine adenosyltransferase 2A Rattus norvegicus
Gene Mep1b meprin A subunit beta Rattus norvegicus
Gene Mgll monoglyceride lipase Rattus norvegicus
Gene Rdh16 retinol dehydrogenase 16 Rattus norvegicus
Gene Rpl30 ribosomal protein L30 Rattus norvegicus
Gene Slc17a1 solute carrier family 17 member 1 Rattus norvegicus
Gene Sod1 superoxide dismutase 1 Rattus norvegicus
Gene Sparc secreted protein acidic and cysteine rich Rattus norvegicus
Gene Timm17a translocase of inner mitochondrial membrane 17A Rattus norvegicus
Gene Ugt1a6 UDP glucuronosyltransferase family 1 member A6 Rattus norvegicus

Additional Information