# A new diagnostic tool for rapid detection and characterization of REPEAT SEQUENCES in inherited diseases

> **NIH NIH R21** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $255,692

## Abstract

=. PROJECT SUMMARY …...
Ataxia is a discoordination of voluntary muscle movement and can be seen as the primary symptom of multiple
disorders including genetic and non-genetic etiologies. Several genes are implicated in causing Spinocerebellar
ataxia through trinucleotide repeat expansions (TREs) and are thought to affect between 1.5 to 4 per 10,000
people globally. Similar trinucleotide repeat expansions in the FMR1 gene, including potentially symptomatic
premutations, can be found in around 1 in 300 people in the United States. Detection of repeat expansion
disorders in a family are important for understanding genetic risks and early detection in at risk members,
especially since unstable repeat expansions lead to the phenomenon of genetic anticipation, where symptoms
can present earlier or more severely across generations. Additionally, several recent studies have suggested
development of targeted therapies specifically targeting expanded repeats as a novel therapeutic target. As
such, earlier and rapid detection of these disorders is crucial for advancing their medical management.
 Traditionally, short TRE targets are assessed via repeat-primed PCR (PR-PCR) and capillary
electrophoresis, while longer mutants are confirmed via Southern blotting. This is clinically important, especially
where repeat lengths outside of the range quantifiable by PR-PCR are diagnostically relevant. Testing for most
TRE genes remains difficult for short read sequencing platforms, where repeat tract lengths exceed average
read length (~100 bp for Illumina systems). Long-read sequencing technologies like PacBio and Oxford
Nanopore have shown success in measuring TREs, however a combination of high costs, large quantities of
DNA input, complex bioinformatics, problems determining repeat region boundaries, and high error rates makes
them an unlikely solution for widespread screening in their current state
 We developed a solution, PRECYSE, based on high-speed atomic force microscopy (HSAFM) paired
with unique ‘nanoparticle barcoding’ that can potentially characterize complex structural variants for numerous
ataxia conditions simultaneously at much lower cost than possible with next generation sequencing (NGS)
sequencing and other emerging approaches. This extremely sensitive technique can be conducted without using
polymerase chain reaction (PCR) and can span a very wide range of possible target sizes, thereby allowing
extension to virtually unlimited molecular lengths. Our hypothesis is that this technology can be easily adapted
to multiplexed detection of TRE targets of practically any length. If successfully developed, our new approach
will change the way clinicians identify, understand, and monitor changes in the genome caused by trinucleotide
repeat expansion diseases through multiplexed panels. At the end of this R21 project, we will have a platform
for multiplexed genomic analysis that successfully purifies and detects trinucleotide repeat targets. However, a
fo...

## Key facts

- **NIH application ID:** 10354657
- **Project number:** 1R21HD107393-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Jason C Reed
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $255,692
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354657

## Citation

> US National Institutes of Health, RePORTER application 10354657, A new diagnostic tool for rapid detection and characterization of REPEAT SEQUENCES in inherited diseases (1R21HD107393-01). Retrieved via MORVS 2026-10-28 from https://api.morvs.ai/grant/nih/10354657. Licensed CC0.

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