The sequenced rat brain transcriptome – its use in identifying networks predisposing alcohol consumption. (16th July 2015)

• Record Type: Journal Article
• Authors: Saba, Laura M.; Flink, Stephen C.; Vanderlinden, Lauren A.; Israel, Yedy; Tampier, Lutske; Colombo, Giancarlo; Kiianmaa, Kalervo; Bell, Richard L.; Printz, Morton P.; Flodman, Pamela; Koob, George; Richardson, Heather N.; Lombardo, Joseph; Hoffman, Paula L.; Tabakoff, Boris
• Is Part Of: FEBS journal. Volume 282:Number 18(2015)
• Page Start: 3556
• Page End: 3578
• Publication Date: 2015-07-16
• Subjects: alcohol consumption -- gene expression -- HXB RI rat strains -- neuroinflammation -- rat selected lines; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.13358
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : A quantitative genetic approach, which involves correlation of transcriptional networks with the phenotype in a recombinant inbred (RI) population and in selectively bred lines of rats, and determination of coinciding quantitative trait loci for gene expression and the trait of interest, has been applied in the present study. In this analysis, a novel approach was used that combined DNA‐Seq data, data from brain exon array analysis of HXB/BXH RI rat strains and six pairs of rat lines selectively bred for high and low alcohol preference, and RNA‐Seq data (including rat brain transcriptome reconstruction) to quantify transcript expression levels, generate co‐expression modules and identify biological functions that contribute to the predisposition of consuming varying amounts of alcohol. A gene co‐expression module was identified in the RI rat strains that contained both annotated and unannotated transcripts expressed in the brain, and was associated with alcohol consumption in the RI panel. This module was found to be enriched with differentially expressed genes from the selected lines of rats. The candidate genes within the module and differentially expressed genes between high and low drinking selected lines were associated with glia (microglia and astrocytes) and could be categorized as being related to immune function, energy metabolism and calcium homeostasis, as well as glial–neuronal communication. The results of the present study show that there are multiple combinations of genetic factors that can produce the same phenotypic outcome. Although no single gene accounts for predisposition to a particular level of alcohol consumption in every animal model, coordinated differential expression of subsets of genes in the identified pathways produce similar phenotypic outcomes. Database: The datasets supporting the results of the present study are available athttp://phenogen.ucdenver.edu Abstract : Using a systems genetics approach, brain RNA expression levels from several populations of rats revealed an association between a predisposition for alcohol consumption and neuroimmune‐related pathways in brain including pathways activated by microglia and astrocytes.