# New technologies for accurate capture and sequencing of repeat-associated regions

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $230,098

## Abstract

Project Summary
Somatic mutations in the brains of patients with Alzheimer’s disease (AD) and other neurological disorders have
been established as a potential mechanism for their pathophysiology. One class of mutations arise from sporadic
mosaicism of retrotransposons, endogenous elements that can mobilize and insert copies into new genomic
locations and have been implicated in the progression of various cancers and disease. Somatic insertions of
retrotransposons are prevalent in individual neurons in the cerebral cortex of the human brain, a region long
associated with AD progression, and recent work has shown a connection between AD-associated Tau protein
mediated mechanisms with retrotransposition activity and somatic mutations. Unfortunately, even though the
apparent association with disease is strong, these types of elements are often ignored in analyses. Because of
their repetitive nature, they have been hard to measure with short read sequencing technologies and any whole-
genome, long-read sequencing technologies have been too costly to apply. In this proposal, we build on the
technology of our parent grant to capture a set of actively moving transposable elements: L1Hs, AluYa5/8,
AluYb8/9, and SVAs. These represent the vast majority of active transposable elements and thus will allow us
to measure the genetic diversity of polymorphic insertions of these elements. After capture, we will use nanopore
long-read sequencing to capture both the entire insertion as well as thousands of bases of surrounding sequence
which will allow for accurate mapping of these elements to the genome. We will apply this technology to multiple
regions from 30 AD brains to allow for follow-up analysis of the enrichment and effect of transposable elements
in AD.

## Key facts

- **NIH application ID:** 10497236
- **Project number:** 3R21HG011493-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Alan P Boyle
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $230,098
- **Award type:** 3
- **Project period:** 2022-06-09 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497236

## Citation

> US National Institutes of Health, RePORTER application 10497236, New technologies for accurate capture and sequencing of repeat-associated regions (3R21HG011493-02S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10497236. Licensed CC0.

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