PROJECT SUMMARY—Genetics Core (Core F) Mendelian mutations, common risk factors, and – more recently – rare risk-associated variants have been identified in neurodegenerative diseases. Yet, a significant proportion of the heritability for Alzheimer's disease (AD) and frontotemporal dementia (FTD) remains unexplained, suggesting that additional genetic risk factors await identification. This PPG Genetics Core has supported PPG investigators over the past ൭൫ years by ൬) collecting and storing DNA and RNA samples from the entire PPG cohort; ൭) providing genetic testing for known pathogenic causes of dementia and risk-associated variants, using both traditional and next-generation sequencing methods; ൮) contributing to the discovery of novel genes and novel risk-associated variants through data generation and case-based screening, using genetic and genomic approaches; and ൯) establishing an informatics platform to facilitate data sharing, storage, and mining, including access to dedicated computational and storage resources. In this renewal application, we propose to leverage this infrastructure and expertise to expand the portfolio of genetic and genomics assays available to the PPG. In the context of expanding roles, we propose to transition primary core activities from UCLA (Geschwind) to UCSF (Yokoyama). We will continue sample collection and banking and will expand our sequencing and genotyping efforts to include whole exome sequencing for gene screening, genome-wide SNP arrays for population mapping, fragment analysis for disease- causing trinucleotide repeat expansions, and transcriptomics in support of Project ൭: Molecular Biomarkers. Such data will be integrated with the clinical, imaging, biomarker, and neuropathological studies being conducted within the PPG to advance our understanding of the genetic architecture of neurodegenerative disease. Given the fundamental nature of genetic information in the etiology and pathophysiology of FTD, this core serves all the projects in this program and is linked to the other PPG cores.