Fig. 6.

Candidate genes for Chr 3 hypothermia from integrative functional genomics. Hierarchical intersections of functional genomic data with positional candidate genes at six loci that overlap the Chr 3 EtOH hypothermia locus, including four mouse loci and two syntenic loci mapped in rat, were generated using the GeneWeaver Phenome Graph function. Terminal nodes represent individual sets of positional candidate genes and published differential expression or coexpression gene sets. Higher-order nodes represent two-way, three-way, and higher-order intersections of these sets, respectively. Genes in the highest nodes are connected to the largest number of gene sets and are thus considered more highly supported candidates by empirical evidence. The six QTLs that overlap with the Chr 3 hypothermia QTL are Alcp3 (Peirce et al. 1998), Ap6q (Tarantino et al. 1998), Letohc1 (Belknap and Atkins 2001), Lore10 (Bennett et al. 2006) from mouse and Alcrsp17 (Radcliffe et al. 2006) and Alcrsp28 (Radcliffe et al. 2009) from rat. The gene expression sets that intersect with positional candidates from the QTL interval are ‘GS128167: Lewis vs. Fischer GABA’ (Sharp et al. 2011) with differential expression in the nucleus accumbens (NA) shell GABA neurons projecting to ventral pallidum in these two strains, ‘GS31783: Gx Corr Neo Cortex’ (Phillips et al. 1994) where the gene expression in BXD Neocortex ILM6v1.1 (Feb08) RankInv microarray data from GeneNetwork.org was correlated with preference for 10% ethanol (g/kg) in a two-bottle choice, ‘GS3647: Et Pref Meta Analysis’ (Mulligan et al. 2006) consisting of genes from the meta-analysis of differential expression in six isogenic and three selected lines with elevated voluntary ethanol consumption, ‘GS87303: Alcohol preferring vs. non-preferring Rats’ (Edenberg et al. 2005) consisting of differential expression in the hippocampus of inbred alcohol-preferring (iP) and -nonpreferring (iNP) rats, and ‘GS128167: DiffExprs EtOH NA’ (Rodd et al. 2008) consisting of differential expression in the NA of inbred alcohol-preferring mice