Genomics

Dataset Information

3

Transcriptional profiling with a Blood Pressure QTL interval-specific oligonucleotide array


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 13.5cM (20Mb) 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 19 out of the 231 positional candidate genes for this QTL are differentially expressed between the two strains tested. Surprisingly, over 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. Pairs of Cy5 and Cy3 labeled targets were co-hybridized onto either the oligonucleotide microarray or a custom TIGR rat cDNA array consisting of 26,401 probe elements representing 20,465 unique non-QTL1b genes. A “flip-dye” design was used as the experimental method of choice to account for potential dye-bias labeling effects. Seven “flip dye” normalized files are submitted for the oligonucleotide array and twelve individual hybridizations are submitted for the cDNA array.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: John P Rapp  Bryan Frank  Kathleen Veratti  Michael R Garrett  Seema Dhindaw  Noah E Letwin  Razvan Sultana  Bina Joe  Norman H Lee 

PROVIDER: E-GEOD-1622 | ArrayExpress | 2010-06-30

SECONDARY ACCESSION(S): GSE1622PRJNA90777

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-1622.README.txt Txt
E-GEOD-1622.idf.txt Idf
E-GEOD-1622.processed.1.zip Processed
E-GEOD-1622.sdrf.txt Txt
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Publications

Transcriptional profiling with a blood pressure QTL interval-specific oligonucleotide array.

Joe Bina B   Letwin Noah E NE   Garrett Michael R MR   Dhindaw Seema S   Frank Bryan B   Sultana Razvan R   Verratti Kathleen K   Rapp John P JP   Lee Norman H NH  

Physiological genomics 20051004 3


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 B  ...[more]

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