# Transposable Element Interaction and Its Impact on Human Development and Health

> **NIH NIH DP5** · BROAD INSTITUTE, INC. · 2024 · $392,120

## Abstract

PROJECT SUMMARY
One of the most surprising discoveries from the Human Genome Project is that only about 1.5% of the genome
codes for proteins, whereas around 46% comprises transposable elements (TEs). Functional assessment of
how these ubiquitous TEs affect human development and health has posed a major challenge. While most TEs
are considered non-functional, or “junk” DNA, here I argue that TE-induced gene regulation is strongly
underestimated due to the historical tendency to explore TE functionality by studying individual TEs
independently of each other. I propose to provide a novel framework to study how interactions between the
hitherto “junk” TE sequences can regulate pre-mRNA splicing to affect gene function, and investigate whether
such a mechanism could substantially affect both human development and evolution, and help explain the
genetic etiology of human diseases. This proposal is inspired from my recent discovery that the interaction
between a pair of Alu retrotransposons may explain the long-sought genetic basis for the evolution of tail loss in
human and apes. Based on this work and my preliminary data, I will first use the Alu pair interaction in TBXT
gene as a model to demonstrate that the interaction between intronic TEs can profoundly impact human
development and health, and explain the etiology of a common genetic disease (Aim 1). Aim 2 proposes to test
the hypothesis that the isoform of TBXT induced by interaction of the Alu pair pleiotropically contributes to
strengthening of hindlimbs, thus directly testing the long-standing hypothesis that the tail-loss evolution in
hominoids is associated with bipedal locomotion evolution (Aim 2). Beyond the specific interaction of the Alu pair
in the TBXT gene, Aim 3 will develop an algorithm called TEILO (Transposable Element Interaction & Local
Organization) to systematically identify the functional TE interactions that affect gene function and human health
by modulating alternative splicing. This work promises to provide a new paradigm to studying the interaction
between TEs and its implication to human health and diseases.

## Key facts

- **NIH application ID:** 10919184
- **Project number:** 5DP5OD033430-03
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Bo Xia
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $392,120
- **Award type:** 5
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919184

## Citation

> US National Institutes of Health, RePORTER application 10919184, Transposable Element Interaction and Its Impact on Human Development and Health (5DP5OD033430-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10919184. Licensed CC0.

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