# Genomics of Cleft Palate

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $711,970

## Abstract

PROJECT SUMMARY/ABSTRACT
Cleft palate (CP) is a common craniofacial structural birth defect caused by the incomplete closure of the
palate (the structure separating the oral and nasal cavities), resulting in feeding, speech, and hearing
problems. CP accounts for 33% of all orofacial clefts (OFCs) or approximately 1 in 1500 babies born
worldwide. Although CP is colloquially used to refer to all types orofacial clefts (e.g. cleft lip or cleft with cleft
palate), CP is embryologically and epidemiologically distinct from orofacial clefts involving the lip, suggesting a
unique genetic etiology. The risk of CP recurrence in first degree relatives is over 50-fold higher than the
population risk, suggesting a strong genetic component. However, there have been a dearth of genetic studies
for CP. Three well-powered genome-wide association studies and meta-analysis have revealed only two
associated loci, neither of which account for a large portion of the genetic heritability in any population. The
lack of common variant associations suggest that the etiology of CP may be similar to other congenital
anomalies, such as congenital heart disease, which often result from de novo mutations, inherited rare
variants, and structural variation. We propose to elucidate the genetic architecture of CP by: (1) analyzing
coding and noncoding de novo, inherited, and structural variants in whole genome sequencing of over 550
case-parent trios in a well-phenotyped, multi-ethnic cohort with CP; (2) integrating these data with
transcriptomic data from mouse and human palate to identify pathways underlying specific CP subtypes; and
(3) determine if CP risk variants/genes show pleiotropic effects in other birth defects and developmental
disorders. This project is poised to rapidly advance our understanding of the genetic etiology of CP and
translate risk to families, and may lead to improved diagnosis and treatment for individuals with CP.

## Key facts

- **NIH application ID:** 10475756
- **Project number:** 5R01DE030342-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** ELIZABETH JANE LESLIE-CLARKSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $711,970
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475756

## Citation

> US National Institutes of Health, RePORTER application 10475756, Genomics of Cleft Palate (5R01DE030342-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10475756. Licensed CC0.

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