Grant: CIHR Fellowship

Rare genetic diseases affect approximately 1 in 40 people, therefore representing a significant societal burden. The genetic cause of thousands of rare diseases remains unsolved. Mosaicism occurs when a cell acquires a genetic mutation at some stage during the development of the embryo, which is then passed on to the offspring of that cell. The result is an individual with two populations of cells with different genetic makeups; some cells will harbour the mutation and others will not. Because the mutation is not present in all cells, it can be difficult to detect using standard diagnostic test. In this project, we will use advanced technological approaches to investigate whether some unsolved rare diseases are caused by mosaic mutations. Deep-DNA sequencing and single-cell sequencing are specialised techniques capable of detecting mosaic mutations. For a group of patients with suspected mosaic disease, I will leverage these techniques to identify the genetic cause and provide an accurate diagnosis. This study will have important implications for affected families, as receiving a genetic diagnosis is imperative for determining the best treatment strategy and supports the psychological and financial well-being of families. Successful outcome of this research will identify new approaches for detecting mosaicism that can be translated into everyday clinical testing of rare disease patients, which will help all affected families receive a genetic diagnosis. In the longer term, understanding the underlying defect of these diseases may lead to the development of targeted therapies.