Ras/MAPK Modifier Loci Revealed by eQTL in .

The oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet, almost all our knowledge on this pathway comes from studies using single genetic backgrounds, whereas mutational effects can be highly background dependent. Therefore, we lack insight in the interplay between genetic backgrounds and the Ras/MAPK-signaling pathway. Here, we used a RIL population containing a gain-of-function mutation in the Ras/MAPK-pathway gene and measured how gene expression regulation is affected by this mutation. We mapped eQTL and found that the majority (∼73%) of the 1516 detected -eQTL were not specific for the mutation, whereas most (∼76%) of the 898 detected -eQTL were associated with the mutation. We detected six eQTL -bands specific for the interaction between the genetic background and the mutation, one of which colocalized with the polymorphic Ras/MAPK modifier Comparison between transgenic lines expressing allelic variants of showed the involvement of in 79% of the -eQTL for genes mapping to this -band. Together, our results have revealed hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.