Nutrition, energy metabolism, and the plasticity of gene expression are linked through the action of epigenetic modifiers that are modulated by cellular metabolites.
When such a change is identified, it can lead to identifying modifier loci that modulate phenotypes, as has recently been done in models for Rett syndrome (Buchovecky et al., 2013; Grillo et al., 2013), leading to a better understanding of pathophysiology and opportunities for therapeutics.
Finally, these results show that rasl11b is a negative modifier that can modulate mesendoderm formation in Zoep mutant.
As shown in Figure 4e, toxicity modifiers are enriched in cell cycle, cytoskeleton, signaling, and protein folding categories; these modifiers are involved in cellular pathways that modulate the level of tolerance to the stress caused by the aggregates and ultimately lead to phenotypic changes.
Furthermore, many of these conditions are heterogeneous, suggesting that the expressivity of gene mutations is modulated by genetic modifiers that play roles in epidermal differentiation.
However, the identified genetic modifiers allow the characterization of biological pathways that modulate the disease and, in some cases, discovery of tractable therapeutic targets.
Because intestinal tumours develop spontaneously in Apc mutant mice they present a powerful model system to study factors that modulate intestinal tumour development, including genetic modifiers, which may be important in the design of potential therapeutic strategies [reviewed [ 28]].
The identification of a gene variant that predisposes mice to renal deterioration after nephron reduction provides a candidate modifier for the elucidation of the complex genetic network that modulate human CKD progression and the design of prognostic biomarkers.
Together, these approaches promise to accelerate the discovery of drugs that modulate instability and that are therefore candidate modifiers of disease.
