Parboosingh, JillianInnes, A. MicheilSmith, Christopher2016-09-062016-09-0620162016Smith, C. (2016). Identifying Novel Causes of Human Neuromuscular Disease (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26432http://hdl.handle.net/11023/3269Neuromuscular diseases (NMDs) are a class of disorders that affect the peripheral nervous system or muscle. These conditions generally result in the loss of voluntary control of movement. They are often genetic, follow Mendelian inheritance, and to date more than 500 causative genes have been identified. Clinical and genetic heterogeneity make correct and specific diagnosis challenging. Identifying novel disease genes will likely improve diagnostic rates, especially as the use of genome scale sequencing techniques in clinical diagnostics increases. Exome sequencing is an extremely powerful tool in Mendelian disease gene discovery. We have leveraged the power of whole exome sequencing in a cohort of 16 individuals with disparate NMDs to: identify novel candidate disease genes (IARS, MSTO1, RAB11FIP2, RNMT), validate previously identified candidate disease genes (MYH14, TAF1, COQ7), propose expansions to the recognized clinical phenotypes of known genes (GLE1, DOK7), and in collaboration with clinical geneticists provide diagnosis to participant patients.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.GeneticsMedicine and SurgeryGeneticsMedical GeneticsNeuromuscular DiseaseCharcot-Marie-Tooth DiseaseExomeGene Discoverymaster thesis10.11575/PRISM/26432