Systems genetics analysis of the LXS recombinant inbred mouse strains:Genetic and molecular insights into acute ethanol tolerance
| Autor: | Colin Larson, Pratyaydipta Rudra, Richard A. Radcliffe, Aaron T. Odell, Phillip A. Richmond, Katerina Kechris, Laura Saba, Robin D. Dowell, Beth Bennett, Shi Wen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Candidate gene Gene Expression Social Sciences Mice 0302 clinical medicine Inbred strain Gene expression Psychology Genetics Regulation of gene expression Multidisciplinary Animal Behavior Organic Compounds Gene Ontologies Neuron projection Brain Chromosome Mapping Genomics Drug Tolerance Chemistry Alcoholism Physical Sciences Medicine Female Transcriptome Analysis Research Article Genotype Science Quantitative Trait Loci Mice Inbred Strains Biology Quantitative trait locus 03 medical and health sciences Astrocyte differentiation Animals Gene Regulation Gene Behavior Ethanol Organic Chemistry Chemical Compounds Biology and Life Sciences Computational Biology Genome Analysis 030104 developmental biology Alcohols Zoology 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 10, p e0240253 (2020) |
| ISSN: | 1932-6203 |
| Popis: | We have been using the Inbred Long- and Short-Sleep mouse strains (ILS, ISS) and a recombinant inbred panel derived from them, the LXS, to investigate the genetic underpinnings of acute ethanol tolerance which is considered to be a risk factor for alcohol use disorders (AUDs). Here, we have used RNA-seq to examine the transcriptome of whole brain in 40 of the LXS strains 8 hours after a saline or ethanol "pretreatment" as in previous behavioral studies. Approximately 1/3 of the 14,184 expressed genes were significantly heritable and many were unique to the pretreatment. Several thousand cis- and trans-eQTLs were mapped; a portion of these also were unique to pretreatment. Ethanol pretreatment caused differential expression (DE) of 1,230 genes. Gene Ontology (GO) enrichment analysis suggested involvement in numerous biological processes including astrocyte differentiation, histone acetylation, mRNA splicing, and neuron projection development. Genetic correlation analysis identified hundreds of genes that were correlated to the behaviors. GO analysis indicated that these genes are involved in gene expression, chromosome organization, and protein transport, among others. The expression profiles of the DE genes and genes correlated to AFT in the ethanol pretreatment group (AFT-Et) were found to be similar to profiles of HDAC inhibitors. Hdac1, a cis-regulated gene that is located at the peak of a previously mapped QTL for AFT-Et, was correlated to 437 genes, most of which were also correlated to AFT-Et. GO analysis of these genes identified several enriched biological process terms including neuron-neuron synaptic transmission and potassium transport. In summary, the results suggest widespread genetic effects on gene expression, including effects that are pretreatment-specific. A number of candidate genes and biological functions were identified that could be mediating the behavioral responses. The most prominent of these was Hdac1 which may be regulating genes associated with glutamatergic signaling and potassium conductance. |
| Databáze: | OpenAIRE |
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