Grant: Doctoral: Vanier Canada Graduate Scholarships

Supervisor: Dr. Jiuyong Xie, University of Manitoba In living organisms, the gene carries the information needed for the cells to function. Changes in this information are known as mutations, and they could result in genetic diseases such as sickle cell anemia. Also, mutations are the major cause of rare disorders that affect a small percentage of people in a region. There are about 7000 rare disorders that affect 1 in 12 Canadians. Unfortunately, how these mutations cause diseases remain unclear. Besides changing protein function, mutations can affect other cell activities. One such activity is alternative splicing (AS), which is a process that identifies and joins the part of the gene that makes protein (exons) and removes the parts that do not (introns). About 95% of human genes undergo AS, and it is estimated that 50% of disease-causing mutations affect AS. AS can either be enhanced or repressed in the cell. This is achieved by a group of proteins that binds to a unique group of DNA in the gene. Our research group has identified one of these DNA groups that repress AS in over 1000 human genes. We named the group REPA-G. However, we are yet to explore if mutations affecting REPA-G are involved in human diseases. My research is aimed at closing this gap. Firstly, I'm going to apply computational techniques in analyzing existing genetic databases to identify and characterize REPA-G mutations. The outcome of this approach is a compilation of REPA-G mutations that will be available for scientists and clinical researchers to better understand the consequence of REPA-G mutations on human disease. Secondly, I will validate the impacts of some of the mutations using wet-lab techniques. Thirdly, I will explore the effect of correcting REPA-G mutations on AS using gene therapy. The findings from my study will aid clinical researchers to understand how genetic mutations affect AS, and use the knowledge to improve the diagnosis and treatment of genetic diseases.