Developing a resource for investigations into the penetrance of disease-causing genomic variants

'How severely will my disease develop?'

'How long will I have my sight for?'

'My brother and father lost their sight at 20, will I as well?'

Genetic testing has revolutionised the way that individuals with rare and inherited diseases can be diagnosed and managed, but these important questions are frequently asked by patients in eye genetic clinics across the world and will become more frequent as the availability and accessibility to genetic testing increases. However, as a scientific community we have very few robust answers as to why despite inheriting the same disease-causing spelling mistakes in their DNA - mutations - a son/daughter may develop disease less severely than their father, or in some cases not at all. Through partnership with Sano Genetics, we will develop a resource which is rich in appropriate clinical information and biological samples to help our investigations in this regard. We anticipate that this work will accelerate our knowledge of the way that additional genetic changes impact the presentation and severity of disease, and develop information which is immediately useful for the clinical management of individuals with genetic eye conditions. The project will develop a framework for the resources required to ask these types of complex scientific questions across different clinical specialities.