Sprouty Background Effect

Inbred genetic background significantly influences the expression of phenotypes associated with known genetic perturbations and can underlie variation in disease severity between individuals with the same mutation. However, the effect of epistatic interactions on the development of complex traits, such as craniofacial morphology, is poorly understood. We use the morphometric landmarks associated with a previous FaceBase analysis (Genetic Determinants of Orofacial Shape and Relationship to Cleft Lip/Palate) to 1) quantify the effect of three Sprouty null mutations on craniofacial shape and 2) to quantify how the associated dysmorphology is modulated by three inbred backgrounds. While it is commonly known that a given mutation may have different phenotypic effects across mouse backgrounds, our quantitative results represent an important first step towards elucidating genetic interactions underlying variation in robustness to known genetic perturbations in mice. Taking background effects into account will be necessary to identify genetic and developmental interactions that modulate the severity of craniofacial dysmorphology, because variation in the penetrance or severity of a disease mutation among humans is almost certainly based on similar interactions. In addition, identical micro-CT image and landmarking protocols make this a valuable comparative dataset to the Collaborative Cross mouse dataset of adult mouse morphology already found on FaceBase.