Format

Send to

Choose Destination
FEBS J. 2015 Sep;282(18):3556-78. doi: 10.1111/febs.13358. Epub 2015 Jul 16.

The sequenced rat brain transcriptome--its use in identifying networks predisposing alcohol consumption.

Author information

1
Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA.
2
Laboratory of Pharmacogenetics of Alcoholism, Molecular & Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
3
Neuroscience Institute, National Research Council of Italy, Section of Cagliari, Monserrato, Italy.
4
Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, Helsinki, Finland.
5
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
6
Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
7
Department of Pediatrics, University of California, Irvine, Irvine, CA, USA.
8
Committee on the Neurobiology of Addiction Disorders, The Scripps Research Institute, La Jolla, CA, USA.
9
National Supercomputing Center for Energy and Environment, University of Nevada, Las Vegas, Nevada, USA.
10
Department of Pharmacology, University of Colorado Denver, Aurora, CO, USA.

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 at http://phenogen.ucdenver.edu.

KEYWORDS:

HXB RI rat strains; alcohol consumption; gene expression; neuroinflammation; rat selected lines

PMID:
26183165
PMCID:
PMC4573833
DOI:
10.1111/febs.13358
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center