# The Genetic Landscape of Human Tooth Agensis

> **NIH NIH R56** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $96,034

## Abstract

PROJECT SUMMARY
The goal of this project is to discover candidate causal genetic variants for human tooth agenesis (TA), a common
craniofacial birth defect that affects ~200 million humans worldwide and imposes significant esthetic, functional,
psychosocial, and financial burdens for affected individuals. Despite research progress, mutations in known TA
genes account for less than 50% of all cases, suggesting that additional causal genes remain to be found.
Genome-wide studies of TA are scarce and, in addition, interpretation of identified variants has been challenging
due to the paucity of studies combining gene discovery with functional genomic approaches. This complicates
our understanding of TA genotype-phenotype correlations and further limits our ability to improve diagnostic and
tooth replacement therapies. In this proposal, we will identify and functionally characterize the underlying genetic
variations in familial and sporadic TA to improve our understanding of the biological pathways involved in the
condition. To achieve our goal, we will: (1) perform whole exome sequencing (WES) of 450 individuals from our
well-characterized TA families and case-control cohort, and apply robust bioinformatic analysis integrating
publicly available data to identify putative causal variants, (2) characterize prioritized variants using functional
genomic approaches in vitro, and (3) apply a PheWAS approach (phenome-wide association study) to determine
the broader clinical significance of TA genes by linking TA genetic variants with additional health outcomes
captured through a large DNA databank (BioVu Biobank). This study combines genome-wide discovery with
biological experimentation, and leverages existing resources (DNA samples, genetic and phenotypic data from
BioVu, established in vitro model) within a multi-pronged framework to identify novel TA genes/pathways.
Therefore, this study is not only innovative in its approach, but in its capacity to overcome the limitations of
traditional TA candidate gene studies. We have exciting published and unpublished data in support of these
proposed studies that will greatly enhance our understanding of the molecular mechanisms underlying TA and
provide the scientific basis for the development of patient-centered diagnostic and future translational research
on tooth replacement therapies. Finally, this study directly addresses the NIDCR's notice of special interest in
“Supporting Discovery Of Genetic Variants Underlying Dental, Oral and Craniofacial Diseases and Conditions”.

## Key facts

- **NIH application ID:** 10453475
- **Project number:** 1R56DE028302-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Jennifer Below
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $96,034
- **Award type:** 1
- **Project period:** 2021-08-20 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453475

## Citation

> US National Institutes of Health, RePORTER application 10453475, The Genetic Landscape of Human Tooth Agensis (1R56DE028302-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10453475. Licensed CC0.

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