Transcriptional profiling with a blood pressure QTL interval-specific oligonucleotide array
Open Access
- 17 November 2005
- journal article
- research article
- Published by American Physiological Society in Physiological Genomics
- Vol. 23 (3) , 318-326
- https://doi.org/10.1152/physiolgenomics.00164.2004
Abstract
Although the evidence for a genetic predisposition to human essential hypertension is compelling, the genetic control of blood pressure (BP) is poorly understood. The Dahl salt-sensitive (S) rat is a model for studying the genetic component of BP. Using this model, we previously reported the identification of 16 different genomic regions that contain one or more BP quantitative trait loci (QTLs). The proximal region of rat chromosome 1 contains multiple BP QTLs. Of these, we have localized the BP QTL1b region to a 13.5-cM (20.92 Mb) region. Interestingly, five additional independent studies in rats and four independent studies in humans have reported genetic linkage for BP control by regions homologous to QTL1b. To view the overall renal transcriptional topography of the positional candidate genes for this QTL, we sought a comparative gene expression profiling between a congenic strain containing QTL1b and control S rats by employing 1) a saturated QTL1b interval-specific oligonucleotide array and 2) a whole genome cDNA microarray representing 20,465 unique genes that are positioned outside the QTL. Results indicated that 17 of the 231 positional candidate genes for this QTL are differentially expressed between the two strains tested. Surprisingly, >1,500 genes outside of QTL1b were differentially expressed between the two rat strains. Integrating the results from the two approaches revealed at least one complex network of transcriptional control initiated by the positional candidate Nr2f2. This network appears to account for the majority of gene expression differences occurring outside of the QTL interval. Further substitution mapping is currently underway to test the validity of each of these differentially expressed positional candidate genes. These results demonstrate the importance of using a saturated oligonucleotide array for identifying and prioritizing differentially expressed positional candidate genes of a BP QTL.Keywords
This publication has 43 references indexed in Scilit:
- Combined Genealogical, Mapping, and Expression Approaches to Identify Spontaneously Hypertensive Rat Hypertension Candidate GenesHypertension, 2005
- Reduction of Gstm1 Expression in the Stroke-Prone Spontaneously Hypertension Rat Contributes to Increased Oxidative StressHypertension, 2005
- Identification of Hypertension-Related Genes Through an Integrated Genomic-Transcriptomic ApproachCirculation Research, 2005
- Isolation of a Chromosome 1 Region Affecting Blood Pressure and Vascular Disease Traits in the Stroke-Prone Rat ModelHypertension, 2003
- Erythrocyte Sodium-Lithium Countertransport and Blood PressureHypertension, 2003
- Microarray Analysis of Rat Chromosome 2 Congenic StrainsHypertension, 2003
- Identifying differentially expressed genes using false discovery rate controlling proceduresBioinformatics, 2003
- Gene Expression Profiling in Hypertension ResearchHypertension, 2003
- High-Resolution Mapping of the Blood Pressure QTL on Chromosome 7 Using Dahl Rat Congenic StrainsGenomics, 2001
- Congenic Substitution Mapping Excludes Sa as a Candidate Gene Locus for a Blood Pressure Quantitative Trait Locus on Rat Chromosome 1Hypertension, 1999