# Impact of coding and non-coding variation in progressive supranuclear palsy

> **NIH NIH UH3** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $780,382

## Abstract

Abstract
A broad range of neurodegenerative conditions, including AD and many ADRDs, such as PSP, FTLD are
collectively known as “tauopathies” because the tau protein is a core feature of these diseases. Further, the
MAPT locus is a major genetic risk factor for Frontemporal lobar degeneration (FTLD) spectrum disorders,
including Progressive Supranuclear Palsy (PSP). Our parent grant involves extensive genomic analyses in PSP
to identify new causal risk factors and understand their genetic mechanisms. Here, we propose a supplement
leveraging many of the same approaches used in the parent grant to comprehensively perform genetic and
genomic characterization of a collection of 100 Induced Pluripotent Stem Cell (IPSC) lines with mutations in the
microtubule-associated protein tau (MAPT) and controls. By including a balance of male and female lines,
multiple lines for most of the major mutations, and including isogenic and uncorrected controls, we will provide
an unprecedented resource for ADRD research. We will culture and harvest all patient and edited isogenic IPSC
lines under rigorously standardized, highly controlled conditions for downstream genetic and genomic analyses.
We will use a multi-omics approach involving whole genome sequencing, bulk and single cell transcriptional
profiling and epigenetic assays, including genome wide methylation and single cell ATAC-seq. By providing deep
quality control and molecular phenotyping in this unique set of IPSC lines, the data production supported by this
supplement will define the quality and integrity of the lines and enable the study of the mechanism (s) by which
genetic variants influence convergent ADRD pathways. These lines will be deposited at NHCDR, and the deep
genomic and epigenetic phenotyping and genetic data will be made publicly available in a coordination with
NINDS staff.

## Key facts

- **NIH application ID:** 10402076
- **Project number:** 3UH3NS104095-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** DENNIS WILLIAM DICKSON
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $780,382
- **Award type:** 3
- **Project period:** 2017-09-25 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402076

## Citation

> US National Institutes of Health, RePORTER application 10402076, Impact of coding and non-coding variation in progressive supranuclear palsy (3UH3NS104095-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10402076. Licensed CC0.

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