Long-range cis-regulatory elements controlling GDF6 expression are essential for ear development

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dc.authoridduman, duygu/0000-0001-7583-0349
dc.authoridatli, emine ikbal/0000-0001-9003-1449
dc.authoridColbert, Brett/0000-0002-9668-0674
dc.authoridSineni, Claire/0000-0003-4719-2815
dc.authoridBademci, Guney/0000-0002-4052-8833
dc.authoridAbad, Clemer/0000-0002-9434-1337
dc.authorid, shengru/0000-0003-4141-6267
dc.authorwosidErgin, Filiz Basak/JEP-6180-2023
dc.authorwosidduman, duygu/AAF-8093-2020
dc.authorwosidTekin, Mustafa/ABG-7627-2020
dc.authorwosidatli, emine ikbal/AAN-5060-2020
dc.authorwosidDemir, Selma/A-1500-2018
dc.contributor.authorBademci, Guney
dc.contributor.authorAbad, Clemer
dc.contributor.authorCengiz, Filiz B.
dc.contributor.authorSeyhan, Serhat
dc.contributor.authorIncesulu, Armagan
dc.contributor.authorGuo, Shengru
dc.contributor.authorFitoz, Suat
dc.date.accessioned2024-06-12T11:19:00Z
dc.date.available2024-06-12T11:19:00Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description.abstractMolecular mechanisms governing the development of the mammalian cochlea, the hearing organ, remain largely unknown. Through genome sequencing in 3 subjects from 2 families with nonsyndromic cochlear aplasia, we identified homozygous 221-kb and 338-kb deletions in a noncoding region on chromosome 8 with an approximately 200-kb overlapping section. Genomic location of the overlapping deleted region started from approximately 350 kb downstream of GDF6, which codes for growth and differentiation factor 6. Otic lineage cells differentiated from induced pluripotent stem cells derived from an affected individual showed reduced expression of GDF6 compared with control cells. Knockout of Gdf6 in a mouse model resulted in cochlear aplasia, closely resembling the human phenotype. We conclude that GDF6 plays a necessary role in early cochlear development controlled by cis-regulatory elements located within an approximately 500-kb region of the genome in humans and that its disruption leads to deafness due to cochlear aplasia.en_US
dc.description.sponsorshipNIH [R01DC009645, R01DC012836, R01DC015052]; National Institute for Health Research (NIHR) Manchester Biomedical Research Centreen_US
dc.description.sponsorshipThis work was supported by NIH R01DC009645 and R01DC012836 to MT and R01DC015052 to CCM, and funding from the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre to CCM.en_US
dc.identifier.doi10.1172/JCI136951
dc.identifier.endpage4217en_US
dc.identifier.issn0021-9738
dc.identifier.issn1558-8238
dc.identifier.issue8en_US
dc.identifier.pmid32369452en_US
dc.identifier.scopus2-s2.0-85089042885en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage4213en_US
dc.identifier.urihttps://doi.org/10.1172/JCI136951
dc.identifier.urihttps://hdl.handle.net/20.500.14551/25044
dc.identifier.volume130en_US
dc.identifier.wosWOS:000579425000002en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Soc Clinical Investigation Incen_US
dc.relation.ispartofJournal Of Clinical Investigationen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectHearingen_US
dc.subjectMutationsen_US
dc.subjectDefectsen_US
dc.subjectCellsen_US
dc.titleLong-range cis-regulatory elements controlling GDF6 expression are essential for ear developmenten_US
dc.typeArticleen_US

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