Genetic analysis in families with neurological disease

National Institute On Aging

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Abstract

Our current efforts revolve around whole genome sequencing within families with neurological disease; this is primarily centered on young-onset, and probably autosomal recessive, forms of common neurological diseases, with a focus on Parkinson's disease, Alzheimer's disease, frontotemporal dementia, atypical dementias, and ataxias. This work has resulted in the assessment of known loci in new families. These families have included those with varied forms of ataxia, young-onset Parkinson disease, and essential tremor. In addition, we have extended our work to generate whole genome sequence data for Parkinson's disease patients and controls, to be shared through the Accelerating Medicines Partnership for Parkinson's disease (AMP-PD); data from several thousand subjects has been shared through this public-private partnership. We have formed the Global Parkinson's Genetics Program (GP2) through the Aligning Science Across Parkinson's (ASAP) initiative. GP2 aims to genotype >150,000 volunteers around the world to further understand the genetic architecture of Parkinson's disease. One arm of GP2 focuses on accelerating the identification of genetic causes of monogenic PD in multiplex families with a history of the disorder. The GP2 Monogenic Hub will collect >5000 samples from families, patients, and patient-parent trios with suspected monogenic PD. These cases will undergo array-based genotyping to identify patients with mutations in known PD genes. Members of the CARD Advanced Analytics team have been contributing to these global data sharing and harmonization efforts through cloud engineering, data management and harmonization of large scale sequencing efforts for collaborative projects, such as GP2 and RedLat.