Beginning with the selection of the long-sleep and short-sleep mice (see references in McClearn & Kakihana 1981), there is a long record of using outbred animals as the founders for ethanol-related selective breeding (Crabbe et al. 2016). The current study continues this strategy using a founder population (the HS-CC) that is three to four times more genetically diverse than other HS populations such as the HS/NPT or HS/Ibg (Hitzemann et al. 1994; Roberts et al. 2007). As noted above, there was a prediction that by using a substantially more diverse founder population, new pathways/mechanisms associated with preference consumption would be detected and these in turn could lead to novel therapeutic strategies. However, much of the data suggest that rather than detecting novel pathways, a more genetically diverse population engages familiar pathways but from novel perspectives. This conclusion is consistent with our observation that when comparing striatal gene regulation among F2, HS4 and HS-CC mice (Iancu et al. 2010) module annotation is more consistent than the alignment of genes within specific modules. For example, Ras/MAPK pathways have been repeatedly associated with
