An article by Boycott et al. in the American Journal of Human Genetics details the current and future bottlenecks to gene discovery and suggests strategies for enabling progress in this regard.
The application of whole genome sequencing (WGS) and whole exome sequencing (WES) has increased the rate of discovery per year of new genes responsible for rare genetic diseases, enabling the identification of almost 3 times more genes compared than conventional methods. Additionally, the proportion of new disease-gene relations has also steadily increased, although a decline in the discovery rate has been observed in recent years.
There remain a non-trivial number of well-known rare diseases for which the causal genetic mechanism remains elusive despite the use of WES and WGS by multiple groups of investigators. The reasons that such discovery efforts fail most likely include both technical limitations and complex biology. The authors describe ideas to circumvent these issues such as the integration of genomic data into systems biology, the use of model system to facilitate gene discovery, improvement of computational and statistical models for variant identification, and the development of strategies for discovering causal genetic mechanisms.
Achieving the IRDiRC’s goal of of diagnosing all rare genetic diseases will require significant international cooperation and engagement of all relevant stakeholders at a scale the community has never seen before. Engaging clinical laboratories, researchers, and the patient community to share their data will be critical. The engagement of the research community, international coordination and funding of activities will be necessary.
Orphanews June 6, 2017