# Genetic and environmental interactions in craniofacial defects

> **NIH NIH F32** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $69,362

## Abstract

Craniofacial dysmorphologies are among the most common human birth defects. However, the multifactorial
basis of these defects has hindered our identification of culpable genes and toxicants. Thousands of
environment toxicants and genes exist that may interact to cause defects. Environmental exposures likely
occur in mixtures, and genetic variation can sensitize embryos to these toxic mixtures. Thus, the number of
possible interactions that require examination exceeds the hundreds of thousands. While still a dizzying
number of potential interactions, modern transcriptomic approaches provide opportunities to identify those
chemicals and genes most likely to interact. This F32 proposal leverages the high-throughput capabilities of
the zebrafish to characterize co-environmental (aim 1) and gene-environment (aim 2) interactions that cause
craniofacial defects. In aim 1, I will bioinformatically define clusters of toxicants that have correlated
transcriptomic effects to predict pairs or groups of chemicals that are most likely to interact synergistically.
Next, I will test these interactions in vivo using a fluorescent plate reader to measure neural crest defects in
high throughput. In aim 2, I will identify disrupted gene networks that are enriched for genes associated with
craniofacial disease. I will then map each toxicant’s differentially expressed genes onto these gene modules to
define gene-toxicant combinations that are predicted to interact. I will mutate these genes of interest using
CRISPR/Cas9 to rapidly characterize gene-environment interactions. Aim 1 will characterize mechanistically
similar environmental toxicants that can synergize to cause defects, improving risk communication and
providing a direct avenue to birth defect prevention. Aim 2 will define specific susceptibility genes, improving
our ability to identify at-risk human populations. Together, this large-scale identification of chemical and genetic
interactors will greatly advance our understanding of the multifactorial basis of craniofacial birth defects.

## Key facts

- **NIH application ID:** 10234802
- **Project number:** 1F32DE030349-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Joshua L Everson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $69,362
- **Award type:** 1
- **Project period:** 2021-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234802

## Citation

> US National Institutes of Health, RePORTER application 10234802, Genetic and environmental interactions in craniofacial defects (1F32DE030349-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234802. Licensed CC0.

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