Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders.

Interaction partners for Dlg2 extracted using Gene Mania (Warde-Farley et al., 2010) which was accessed as a Cytoscape plugin with default settings. Depicted are top 20 genes related to Dlg2 through physical interactions, colocalizations, or sharing protein domains. Dlg2 which encodes for PSD93, interacts with a number of genes and gene products associated with glutamate receptor activity including Dlg4, Syngap1, Neto, Grin1, Grin2b, Dlgap1, and Dlg3.

Module overlap across brain regions together with enrichment of modules in DE/DV/DW genes. Color from blue to red is proportional to –log10(p) of overlap between module membership (Fisher exact test). A majority of modules have strong counterparts across regions. The affected modules also have an affected counterpart in a majority of cases, although we also find region specific affected modules. (A) CeA – SH; (B) CeA – PL; (C) SH – PL.

Overlap of selection associated DE, DV, and DW genes across three brain regions: CeA, SH, and PL. (A) As indicated in the Venn diagram (B) there was only 5 DE genes common to all three brain regions: 5730455P16Rik,Gdi2, Skiv2, Tsr1, and Glod4. The region and module distribution of these genes is illustrated. The greatest overlap was between the CeA and SH (N = 31). Only annotation of the CeA DE genes revealed a significant enrichment in GO categories that included neuron part, structural constituent of myelin sheath and axon ensheathment. Genes in the neuron part category included Adora1, Chrna4, Crhr1, Drd1a,Gabbr2, Gabrd, Gal, Htr1a, Htr2a, Htr7, Pde1b, Reln, Syt2, and Tac1. (C) Overlap of selection associated DV genes across three brain regions: CeA, SH, and PL. There were 30 significant DV genes common to all three brain regions and this grouping was significantly enriched (FDR < 3 × 10–3) in genes associated with the GO annotation of cell to cell signaling. Genes with this GO annotation included Dlg2, Egr3, Gabbr2, Lnpep, Pcdhgb2, Pcdhac2, Sstr4, and Syt10. The significant DV genes unique to each brain region also showed an enrichment in genes associated with cell to cell signaling. (D) Overlap of selection associated DW genes across three brain regions: CeA, SH, and PL. There were 72 significant DW genes common to all three brain regions and this grouping was significantly enriched (FDR < 5 × 10–3) in genes associated with the GO annotation of post-synapse. Genes with this GO annotation included Chrna7, Als2, Pppir9a, Strn, Kcna4, Kif1a, and Slc1a2. Genes showing unique DW to each of the three brain regions were enriched in genes associated with the GO annotation synapse or synapse part.