# Genetics Core

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $211,399

## Abstract

Genetics Core: Project Summary/Abstract
Genetics Core C of the competing renewal of this Program Project Grant (PPG) entitled “Frontotemporal
Dementias: Genotypes and Phenotypes” aims to continue to build a large well-characterized cohort of DNA
samples, and use and share these samples for cutting-edge genomic applications to foster new genetic
discoveries within and beyond this PPG, which seeks to advance understanding of mechanisms underlying the
onset and progression of hereditary and sporadic forms of frontotemporal degeneration (FTD). FTD manifests
clinically with progressive behavioral and/or language deficits with subtypes classified neuropathologically by
the different disease proteins found as cellular inclusion bodies, of which the most common are TAR DNA
binding protein (TDP-43, FTLD-TDP) and tau (FTLD-tau). Autosomal dominant forms of FTD have been
identified with mutations most commonly in MAPT, GRN, and C9orf72, and each is associated with a specific
FTLD pathological subtype, for example, GRN and C9orf72 mutations with FTLD-TDP and MAPT mutations
with FTLD-tau. In addition, genetic risk factors, such as TMEM106B, have been identified. Studying the
genetics of FTD can help to elucidate its etiology and pathophysiology as well as identify genetic factors that
increase risk for disease or modify its phenotype. New evidence for protein aggregation and spread throughout
the CNS in FTD and other NDs (studied in Projects 3 and 4) provides a promising target for therapeutic
development for these currently incurable disorders. However, accurate, as well as rapid, ante mortem
diagnosis of FTD underlying pathology is crucial for this effort. A personalized medicine approach that
combines genetic information with other biomarkers (imaging, biofluids) to better define FTD clinical
endophenotypes will enhance power for clinical trials focused on slowing or preventing progression of spread
of tau, TDP-43 and other FTLD-associated pathologies. To enable genetic studies of FTD in this PPG, Core C
will collect and bank DNA from Clinical Core B subjects and autopsy brains characterized in Neuropathology
and Biomarker Core D. DNA will be used for genetic analysis by Core C and Project 2 and be available to
share with other collaborators. Genetic mutations and SNP risk factor data, will be used by Project 1 to assess
factors contributing to rate of disease progression. Genotype data will enable selection of cases (either
inclusion or exclusion of cases with a mutation, for example) for study in Projects 1-4. In addition, genetic data
will enable clinical, pathologic and genetic correlations with data from Projects 1-4 and Cores B and D.
Biostatistics and Data Management Core E will perform statistical analysis for these studies. Genomic analysis
at the exome and genome level will be used to identify new genes in families without an identified mutation and
for additional genomic association studies both within this PPG and in local, national, and intern...

## Key facts

- **NIH application ID:** 9891007
- **Project number:** 5P01AG017586-20
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** VIVIANNA M VAN DEERLIN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,399
- **Award type:** 5
- **Project period:** — → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891007

## Citation

> US National Institutes of Health, RePORTER application 9891007, Genetics Core (5P01AG017586-20). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9891007. Licensed CC0.

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