Using gene network analysis to identify novel candidate genes for Congenital Diaphragmatic Hernia (CDH).

Document Type


Publication Date

Summer 2017

JAX Location

In: Student Reports, Summer 2017, Jackson Laboratory


Congenital Diaphragmatic Hernia (CDH) is a birth defect that affects every 1 in 3000 births that often leads to infant mortality1,2. CDH is characterized by the malformation of the diaphragm, and sometimes lungs and heart. Currently, there are more than 60 genes that have been identified as contributing to CDH on the basis of mouse phenotypes and genetic characterization of affected individuals!' 2, 3, 4. Recent genome sequencing results obtained by our collaborators for over six hundred trios (affected patients and their parents) identified hundreds of de novo mutations in patients with CDH5,6. The goal of this project was to use bioinformatics approaches to identify the most likely disease relevant genes from this unique gene set. Gene network analysis implicated four of the genes in the de novo set based on their putative functional relationships to genes previously associated with CDH phenotypes: Emx2, Meis2, Sma, and Myr! (aka, Gm98). Of these, Emx2 was selected as the a primary gene of interest. The validation of Emx2 as a candidate CDH gene will be accomplished by creating a mutant mouse by genome editing via CRISPRlCas9. The experimental results from these CRISPRlCas9 mice will help bridge the gap in knowledge about what causes CDH and how we can treat its adverse effects to decrease the infant mortality rate that is a result from this disease.

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