A Comprehensive Network and Pathway Analysis of Human Deafness Genes
2013 (English)In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 34, no 5, p. 961-970Article in journal (Refereed) Published
Abstract [en]
Objective: To perform comprehensive network and pathway analyses of the genes known to cause genetic hearing loss.
Study Design: In silico analysis of deafness genes using ingenuity pathway analysis (IPA).
Methods: Genes relevant for hearing and deafness were identified through PubMed literature searches and the Hereditary Hearing Loss Homepage. The genes were assembled into 3 groups: 63 genes that cause nonsyndromic deafness, 107 genes that cause nonsyndromic or syndromic sensorineural deafness, and 112 genes associated with otic capsule development and malformations. Each group of genes was analyzed using IPA to discover the most interconnected, that is, "nodal" molecules, within the most statistically significant networks (p < 10(-45)).
Results: The number of networks that met our criterion for significance was 1 for Group 1 and 2 for Groups 2 and 3. Nodal molecules of these networks were as follows: transforming growth factor beta1 (TGFB1) for Group 1, MAPK3/MAPK1 MAP kinase (ERK 1/2) and the G protein coupled receptors (GPCR) for Group 2, and TGFB1 and hepatocyte nuclear factor 4 alpha (HNF4A) for Group 3. The nodal molecules included not only those known to be associated with deafness (GPCR), or with predisposition to otosclerosis (TGFB1), but also novel genes that have not been described in the cochlea (HNF4A) and signaling kinases (ERK 1/2).
Conclusion: A number of molecules that are likely to be key mediators of genetic hearing loss were identified through three different network and pathway analyses. The molecules included new candidate genes for deafness. Therapies targeting these molecules may be useful to treat deafness.
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2013. Vol. 34, no 5, p. 961-970
Keywords [en]
Deafness genes, ERK 1/2, GPCR, HNF4A, MAPK1, Molecular pathways analysis, TGFB1
National Category
Otorhinolaryngology Neurology
Identifiers
URN: urn:nbn:se:oru:diva-82030DOI: 10.1097/MAO.0b013e3182898272ISI: 000330371400032PubMedID: 23770690Scopus ID: 2-s2.0-84880897755OAI: oai:DiVA.org:oru-82030DiVA, id: diva2:1432139
Note
Funding Agencies:
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute on Deafness & Other Communication Disorders (NIDCD)
K08 DC010419
Bertarelli Foundation
2020-05-262020-05-262020-05-26Bibliographically approved