# Genomic and Gene Expression Analyses to Discover Human CDH Genes and Pathways

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $279,407

## Abstract

PROJECT I: GENOMIC AND GENE EXPRESSION ANALYSES TO DISCOVER GENES AND
PATHWAYS IN HUMAN CONGENITAL DIAPHRAGMATIC HERNIA
ABSTRACT:
 This project focuses on the characterization of genomic variation in human patients with congenital
diaphragmatic hernia (CDH) to identify novel genes and pathways causing CDH. We will use whole genome
sequencing (WGS) and whole exome sequencing (WES) to identify rare and predicted pathogenic de novo and
inherited sequence, copy number, and structural variants in sporadic CDH cases, and inherited variants in
families containing more than one affected individual. A challenge in studying CDH, like most birth defects, has
been its genetic heterogeneity. To overcome this obstacle, we have maximized our sample size by combining
two well-established CDH research studies, generating one of the largest and most well-characterized cohorts
of patients with CDH in the world. We have recruited 1500 patients to date, with WES or WGS data completed
or in the pipeline for approximately 800 proband-parent trios. We show that this will provide sufficient power to
identify multiple CDH genes with statistical significance. These data will be analyzed using novel and well-
established bioinformatics tools to prioritize variants and identify molecular pathways that are likely to be
disease-associated. In addition, the DHREAMS consortium has collected diaphragm specimens from a large
number of patients, allowing for the study of somatic mutations and tissue-specific gene expression changes
that may be associated with genetic subtypes of CDH. Together, the data derived from these large-scale
genomic experiments have already identified key candidate genes that are being pursued in functional
experiments in Projects II and III, and will continue to provide novel candidates that will allow identification of
genotype-phenotype associations, help inform and refine prognosis for patients with CDH, and will elucidate
molecular pathways that could be targets for future therapeutic strategies.

## Key facts

- **NIH application ID:** 9929450
- **Project number:** 5P01HD068250-09
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Wendy K Chung
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $279,407
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929450

## Citation

> US National Institutes of Health, RePORTER application 9929450, Genomic and Gene Expression Analyses to Discover Human CDH Genes and Pathways (5P01HD068250-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9929450. Licensed CC0.

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