# The role of noncoding regulatory variants in orofacial clefts

> **NIH NIH R03** · EMORY UNIVERSITY · 2021 · $156,458

## Abstract

PROJECT SUMMARY
Orofacial clefts (OFCs) are the most common craniofacial birth defect in humans and are caused by multiple
genetic and environmental risk factors. Elucidating the etiology of OFCs is critical not only for our knowledge of
developmental biology and for how clefts arise, but ultimately for improved prevention, treatment, and
prognosis for individuals affected by OFCs. Clinical applications of genome sequencing are growing, but the
usability for OFCs is hindered by a substantial missing fraction of heritable risk and a poor understanding of
how variants in non-coding regulatory elements contribute to OFC risk. These elements include (but are not
limited to) enhancers, promoters, noncoding RNAs (e.g., microRNA), and topologically associated domain
boundaries. Despite the mounting evidence that non-coding regulatory variants are important contributors to
human disease, widespread analysis of such variants in OFCs has been limited by the lack of a large resource
of whole genome sequences in individuals with OFCs and difficulties annotating craniofacial regulatory
variants. In this proposal, we will take advantage of several recent initiatives that directly address these
barriers by analyzing rare de novo, inherited, and structural variants from over 1,300 case-parent trios with
OFCs sequenced through the Gabriella Miller Kids First Research Program. We will integrate these data with
genomic atlases of chromatin profiling, microRNAs, and RNA-seq data generated from human and mouse
craniofacial tissues. These analyses will provide key insights into the genetic architecture of OFCs and will
reveal the full potential of WGS data for OFCs.

## Key facts

- **NIH application ID:** 10302874
- **Project number:** 1R03DE030118-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** ELIZABETH JANE LESLIE-CLARKSON
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $156,458
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302874

## Citation

> US National Institutes of Health, RePORTER application 10302874, The role of noncoding regulatory variants in orofacial clefts (1R03DE030118-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10302874. Licensed CC0.

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