 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Nov 24, 2009 |
| Title |
mRNA Levels in the Rat Liver Display Strain-Specific, Hereditary and AHR-Dependent Components |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
|
| Summary |
Background
The rat is a major model organism in toxicogenomics and pharmacogenomics, and the use of steady-state hepatic mRNA levels to predict and understand drug toxicity and mechanism is well-established. Surprisingly, the inter- and intra-strain variability of rat mRNA expression has not been evaluated, nor has the extent of its hereditability been established. We address these issues by studying three rat strains (Long-Evans, Hans/Wistar, and Sprague-Dawley) and two F2 lines derived from Long-Evans x Hans/Wistar crosses.
Results
Using three independent techniques – variance analysis, linear modelling, and unsupervised pattern recognition – we characterize large amounts of both intra- and inter-strain variability in mRNA levels. Importantly, both sources of variability are highly non-random, and are enriched for specific functional groups. Specific transcription-factor binding-sites are enriched in their promoter regions, and these genes occur in “islands” throughout the rat genome. Using the two F2 crosses we study the hereditability of hepatic mRNA levels and show that the majority of rat genes appear to exhibit directional genetics, with only a small fraction having evidence for interacting loci. Finally, a comparison of inter-strain heterogeneity between mouse and rat orthologs shows more heterogeneity in rats than mice, and find that rat and mouse heterogeneity are uncorrelated.
Conclusions
Our results establish that hepatic mRNA levels are relatively homogeneous within rat strains, but highly variable between them. This variability may be related to increased activity specific transcription-factors, and has clear functional consequences. Future toxicogenomic and pharmacogenomic studies may take advantage of this phenomenon by surveying panels of rat strains.
Keywords: Inter-Strain Comparison
|
| |
|
| Overall design |
We profiled the basal mRNA levels in three strains and two lines of rat, each using four biological replicates.
|
| |
|
| Contributor(s) |
Boutros PC, Moffat ID, Okey AB, Pohjanvirta R |
| Citation(s) |
21760882 |
| Submission date |
Feb 08, 2008 |
| Last update date |
Mar 03, 2017 |
| Contact name |
Paul C Boutros |
| E-mail(s) |
Paul.Boutros@utoronto.ca
|
| Organization name |
Ontario Institute for Cancer Research
|
| Street address |
101 College Street, Suite 800
|
| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 0A3 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL341 |
[RAE230A] Affymetrix Rat Expression 230A Array |
|
| Samples (20)
|
|
| Relations |
| BioProject |
PRJNA107999 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10448_RAW.tar |
477.4 Mb |
(http)(custom) |
TAR (of CEL, DAT, EXP) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...