# Treasure Your Exceptions: Investigating Rare Diseases Using Whole-Genome Sequencing and Molecular Functional Studies

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $45,520

## Abstract

PROJECT SUMMARY
There are approximately 7,000 defined rare diseases affecting an estimated 30 million Americans and 350 million
people worldwide. The study of rare diseases offers a unique insight into human disease and has been rapidly
improved by the advent of next-generation sequencing (NGS) technologies. Greater than 4000 Mendelian
phenotypes are now associated with causal genes, as catalogued in On Line Mendelian Inheritance in Man
(OMIM). This knowledge, achieved through the high-throughput analysis of genomic data followed by molecular
functional studies, has enhanced our understanding of basic biology and of human disease and offers hope for
those afflicted with such rare diseases. However, the genetic causes of many Mendelian disorders or traits
remain to be discovered. OMIM describes at least 1,500 Mendelian phenotypes of unknown molecular etiology,
and another 1,700 that are likely to be Mendelian and remain undiagnosed in affected individuals. The diagnostic,
odyssey, as it is called, for these individuals is a cycle of multiple misdiagnoses and often result in no diagnoses,
treatments, or interventions. These cases represent the potential to enhance our knowledge of human biology.
The Treasure Your Exceptions (TYE) program at Emory University is dedicated to discovering novel mutations
in genes causing novel Mendelian disease phenotypes or traits through the use of next-generation sequencing
technologies. We currently have 13 families with unique genetic diseases enrolled in the program with widely
varying phenotypes. In the past year we have successfully identified a strong candidate variant (p.Y401C) in the
DUSP7 gene for a rare case of severe short stature and insulin resistance. Discovery of this variant was achieved
through the development of a custom and adaptable computational pipeline for analysis of genomic data.
Consequently, additional families in TYE are now able to be analyzed in a similar manner while I follow up on
our initial discovery with functional studies to demonstrate causality. Computational analysis of genomic data to
identify causal variants for rare diseases followed by proof of causality afford the opportunity to elucidate the
genetic etiology of these diseases and related common diseases to aid in developing diagnostic measures and
therapeutics, as well as gain insight into basic human biology. Thus, I propose to analyze three TYE families
presenting with 1.) a lethal form of Desbuquois-like dysplasia, 2.) hypersomnia, ataxia, and cognitive impairment,
and 3.) inherited breast cancer, respectively. Additionally, I propose to determine the functional consequences
of the candidate variant on DUSP7. In Aim 1, I will perform variation detection to identify candidate causal
variants for the diseases described above using whole-genome sequencing and genome mapping followed by
comprehensive computation analysis using the pipeline I developed. In Aim 2, I will use an in vitro phosphatase
assay and cellular growth ...

## Key facts

- **NIH application ID:** 9842271
- **Project number:** 5F31GM131609-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Trenell Mosley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842271

## Citation

> US National Institutes of Health, RePORTER application 9842271, Treasure Your Exceptions: Investigating Rare Diseases Using Whole-Genome Sequencing and Molecular Functional Studies (5F31GM131609-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842271. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*