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Series GSE10448 Query DataSets for GSE10448
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)
GSM265380 liver-SpragueDawley-control rep1
GSM265381 liver-SpragueDawley-control rep2
GSM265382 liver-SpragueDawley-control rep3
Relations
BioProject PRJNA107999

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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

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