TRANSLATIONAL RESEARCH GRANT

During the last decade, a revolution in the techniques used to sequence and analyse our DNA has seen dramatic improvements in our ability to determine the genetic cause of mitochondrial
diseases and other inherited disorders. However, despite these technological advances, there are still many that we have not solved. At present, perhaps half or more of paediatric mitochondrial disease cases still do not receive a diagnosis. Limitations include difficulties in proving that a specific genetic change or gene is responsible for a disease, along with technical challenges that result in some diagnoses being missed. Our ongoing investigations use multiple approaches to help us overcome current limitations to achieve the highest diagnostic rates possible. We envision that our studies exploring overlapping functional genetics approaches will help to improve the diagnosis rates and provide pathways to translate these studies for both clinical and research benefit.

However, all of these current approaches are still hampered by technical limitations that prevent the detection or precise characterisation of more complicated genetic alterations. This application seeks to address this knowledge gap by expanding our current studies to include one of the newest DNA sequencing strategies, known as Long-Read DNA Sequencing. This rapidly developing technology can provide additional genetic information that we cannot obtain from our current approaches, but its clinical utility is still in its infancy. Therefore, we will evaluate this new genetic technique alongside our other methodology, further maximizing our ability to provide a diagnosis to patients and families with mitochondrial disease.