Grant: Doctoral: Vanier Canada Graduate Scholarships

Mutations in many of the ~22,000 genes in human DNA cause rare genetic disorders which affect as many as one million Canadians. Over half of the known genetic disorders still have no identified cause or effective treatments, thus placing a burden on patients and the healthcare system. Genetic diseases can be further complicated by environmental factors. For instance, approximately 10% of diabetic mothers give birth to children with birth defects, nearly three times the average rate. Prevailing thought is that this is due to perturbations in the expression of DNA as a result of exposure to a high sugar environment. Femoral Facial Syndrome (FFS) is a rare genetic disorder whose cause remains unknown. FFS is also frequently associated with diabetic pregnancies, suggesting that multiple risk factors are important for this disease. For this project, I will discover the genetic and environmental causes, and investigate possible prevention strategies for FFS. Six families affected by FFS have been identified, and I will use modern powerful DNA sequencing technology to identify the disease-causing gene(s). To better understand this disease, I will explore the effect this mutation has on the cellular environment using human cells and mice. Finally, I will explore preventative strategies, namely by evaluating whether optimal control of maternal diabetes can reduce the risk FFS. Knowledge gained from this research will directly enhance the clinical management of FFS and potentially provide insight into preventative options. In the broader sense, it will enhance our understanding of the additive roles of genes and fetal environment on human development.