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Chunk #28 — Discussion

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Effects of selection for ethanol preference on gene expression in the nucleus accumbens of HS-CC mice.
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The DV gene expression statistic is one approach for assessing whether there are differences in the regulation of gene expression between groups. Mar et al. (2011) have suggested that the variance in gene expression may be far more important in understanding disease etiology than previously recognized. Further, these authors noted that genes with high expression variability tend to function as cell surface receptors. In the current data set, we observed that 223 genes showed significant DV between the high and low preference lines, and consistent with Mar et al. (2011), this group of genes was enriched for cell–cell signaling, synaptic signaling and signaling receptor activity (Table S5). Importantly, for this group of genes, higher variability was significantly skewed to the high preference line (high vs. low: 208 vs. 15). Numerous members of the signaling receptor activity genes, including Chrna7, Gabrb2, Grin2a, Grin2b, Fzd3, Htr2a, Igf1r, Kit, Oprd1 and Sort1, have been associated with one or more alcohol phenotypes, including preference (Bowers et al. 2005; Bubier et al. 2014; Cao et al. 2014; de la Monte et al. 2012; Dick et al. 2006; Enoch 2013; Lo et al. 2016; Mulligan et al. 2006; Zhang et al. 2008).