Network-based prediction of novel genes for congenital diaphragmatic hernia (CDH)


Angelina Guerra

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In: Student Reports, Summer 2019, The Jackson Laboratory


Congenital Diaphragmatic Hernia (CDH) (OMIM 142340) is a fairly common, life threatening birth defect occurring in I out of every 3,000 live births, in which a deformation in the diaphragm allows for an opening in the diaphragm that allows the liver to penetrate into the thoracic cavity. Lung hypoplasia and hypertension arc common comorbidities and are the most common cause of death in CDJ-1 patients2.3. CDH may present as an isolated 0efect however in 40% of cases occurs in tandem with other anomalies. Over 100 genes have been implicated in the development of CDH, however the mechanistic function of these genes in the development of this defect is unclear. Currently the cause of CDH is unknown. Based on mouse and Human data, over 100 genes have been implicated in CDH. However, these genes only explain a narrow portion of CDH cases. It was estimated that over 400 genes had a possible association to CDH. To further the discovery of novel CDH genes, protein association networks and machine learning was utilized to undergo a meta-systemic analysis of known genes implicated in the development and deformation of the diaphragm. Novel genes were then matched with genes implicated from de nova sequencing data from patient cases sourced from de novo gene variants identified in multiple patient sequencing efforts. These results grant further insights into the genomic structure of CDH and provide novel gene and pathway evidence to further our understanding of this elusive birth defect The use of a multifaceted tool approach assisted in elucidating the etiology in current cases of both isolated and syndromic CDH through the matching of novel network-predicted genes and patient data.

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