The Monogenic Hub aims to identify novel genetic causes of apparently monogenic Parkinson’s disease (PD) – forms of PD where pathogenic variants in a single PD-linked gene are considered causative of the disease. The Monogenic Hub is comprised of the groups Sample Prioritization, Data Analysis, and Portal Development.
Leveraging GP2’s global network of researchers contributing patient samples, the Monogenic Hub will collect thousands of patients and relatives from families in whom a monogenic cause is suspected. Emphasis will be placed on families from underrepresented populations. All currently known PD genes have been found in various populations around the globe, however, some occur at highly variable and population-specific frequencies. The most striking example being the G2019S mutation in the LRRK2 gene. In addition, it is conceivable that population-specific hereditary forms of PD may exist, as exemplified by X-linked dystonia-parkinsonism, a condition exclusively present in patients of Filipino ancestry.
The Monogenic Hub will collect families and singleton cases, as well as parent-offspring trios, through the Monogenic Portal. These will be prioritized by Sample Prioritization for whole-genome sequencing or long-read sequencing based on a number of different criteria, such as family history, availability of samples from several affected family members, age at onset and ethnicity. The Data Analysis group will analyze genome data for the presence of potentially novel pathogenic variants.
Progress so far
- Created Monogenic network
- Negotiated whole-genome sequencing (WGS) prices with vendors
- Piloted WGS 500 potential monogenic samples
Remaining Year 1 Goals
- Final selection of monogenic samples
- Continue to expand the network and involve more groups
- Start to validate potential new variants identified via WGS (wet-lab)
- Provide regular updates to sample submitters