PSP and CBD Genetics

We plan to analyze whole exome and whole genome sequence data generated from subjects with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Alzheimer's disease (AD) and elderly normal controls. The goal is to detect mutations and variants that cause, contribute to risk, or protect against PSP and/or CBD. We want to compare PSP and CBD genotypes to those from AD and normal controls sequenced by the Alzheimer's Disease Sequence Project. We would like both whole genome and whole exome data from the Alzheimer's Disease Sequence Project for AD and normal controls. We would also like whole genome and whole exome data for PSP and CBD generated by the PSP and Tau consortiums. We will use these data to determine which mutations and variants are associated with PSP or CBD versus benign variants. All PSP and CBD subjects being sequenced are deceased. The requested data sets will have variants recalled as a batch and combined to evaluate allele frequencies of called variants. The AD and control variant frequencies will then be compared to allele frequencies from PSP and CBD subjects as described above. We will also compare structural variants (insertion-deletions, copy number variants, and chromosomal rearrangements) identified in PSP and CBD subjects to those found in AD and in cognitively normal controls in order to determine structural variants involved in PSP and CBD pathogenesis. All of the investigators that are listed will be using a joint called VCF generated from the requested data sets. PSP is a neurodegenerative disease closely related to Alzheimer's disease (AD). PSP, CBD and AD have neurofibrillary tangles as part of the signature neuropathology defining these disorders. PSP and CBD are considered Alzheimer’s Disease Related Disorders (ADRD).

We are attempting to identify all the inherited elements that contribute to progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) risk. To do this we will analyze DNA sequence data from subjects with AD, PSP, CBD, and subjects who are cognitively normal. The sequence data from these groups will be compared to identify differences that contribute to the risk of developing PSP and CBD, or that protect against these diseases. These DNA differences can be at a single site in the genetic code, or can span multiple sites, changing the copy number of DNA sequences. Both types of genetic variants will be examined.