NIH, CurePSP and Tau Consortium PSP WGS

Progressive supranuclear palsy (PSP) is the most common frontotemporal lobar degeneration associated with tau pathology. The majority of patients with PSP can be accurately diagnosed antemortem due to a characteristic clinical syndrome; however, there are atypical clinicopathologic forms of PSP that can mimic Parkinson’s disease, frontotemporal dementia, progressive nonfluent aphasia and corticobasal syndrome. While rare pathogenic variants, common risk factors, and – more recently – rare risk-associated variants have been identified in PSP, a significant proportion of the heritability for neurodegenerative tauopathies and other frontotemporal lobar degenerations remains unexplained, strongly suggesting that additional genetic risk factors await discovery. We assembled PSP samples for whole-genome sequencing (WGS) of neuropathologically characterized PSP, with the majority coming from the Mayo Clinic in Jacksonville. Other major contributors were the University of Pennsylvania and University College London.

The SeqLab Core at the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Uniformed Services University of the Health Sciences (HJF/USU) conducted genomic sequencing of de-identified DNA samples.  Library preparation used the Illumina PCR-free DNA workflow on SeqLab automated Hamilton STAR liquid handling platforms. Clustered libraries were sequenced using the Illumina HiSeq X platform.  FASTQ data were generated and genomic variants called after quality control, alignment and calling performed on HAS 2.0 software algorithm. The Genome Center for Alzheimer’s Disease (GCAD), at the University of Pennsylvania, processed the sequence data using a standardized pipeline.