A community approach to accelerate the discovery of the molecular basis of neurodevelopmental disorders (360G-Wellcome-209083_Z_17_Z)

The molecular causes of the majority of inherited neurodevelopmental disorders remains largely poorly understood, presenting an immense healthcare burden worldwide. The cause of such disorders in rural Pakistan typically relates to founder mutations that have accumulated due to historical ancestral population bottlenecks, followed by population expansion. Together with expert clinical input, this enables greatly empowered phenotypical, genetic and functional studies to discover the molecular causes of autosomal recessive diseases that would otherwise elude discovery, benefiting medical science and aiding disease diagnosis globally. This seed proposal will cement new collaborative relationships established by the applicant and develop infrastructure in four Pakistani Research Centres enabling invaluable new opportunities for novel neurodevelopmental disease gene discoveries. These will unravel important new biomolecular developmental processes for future exploration using stem cell and animal models that will be developed alongside this program. This project also provides opportunities to improve local knowledge of the spectrum and causes of inherited neurodevelopmental disease, greatly facilitating development of diagnostic services in Pakistan. By consolidating these collaborative relationships, while further developing the applicant’s skill set and experience, the proposal will lay foundations for long term future molecular studies to enhance scientific knowledge and define new therapeutic avenues for these devastating disorders.