Selection for drinking in the dark alters brain gene coexpression networks

Area of Science:

• Neurogenetics
• Systems Neuroscience
• Behavioral Genetics

Background:

• Elevated drinking in the dark (DID) in selectively bred mice (HS/NPT) reaches high blood ethanol concentrations (BECs).
• Mechanisms linking genetic differences to DID remain unclear.
• This study investigates the transcriptome to understand genetic influences on DID.

Purpose of the Study:

• To examine transcriptome-wide changes, including differential gene expression (DE) and coexpression patterns.
• To identify genetic loci (QTLs) associated with elevated BECs.
• To differentiate the genetic basis of DID from ethanol preference.

Main Methods:

• Quantitative trait locus (QTL) analysis using the Mouse Universal Genotyping Array.
• Gene expression profiling of the ventral striatum using Illumina Mouse 8.2 array.
• Differential gene expression (DE) analysis and weighted gene coexpression network analysis (WGCNA).

Main Results:

• Significant QTLs for elevated BECs identified on chromosomes 4, 14, and 16.
• Ninety-four transcripts showed differential expression, distinct from known preference genes.
• WGCNA identified two modules with significant selection effects on connectivity, including known ethanol-associated genes.

Conclusions:

• Selection significantly impacted gene coexpression patterns, more so than differential gene expression.
• Identified QTLs and DE genes are distinct from those associated with ethanol preference.
• Suggests a marked genetic divergence between the DID and preference phenotypes.