Show simple item record

dc.contributor.authorLanillos, Javier
dc.contributor.authorSantos, María
dc.contributor.authorCarcajona, Marta
dc.contributor.authorRoldan-Romero, Juan María
dc.contributor.authorMartinez, Angel M
dc.contributor.authorMonteagudo, Maria 
dc.contributor.authorLeandro-García, Luis Javier
dc.contributor.authorMaietta, Paolo
dc.contributor.authorAlvarez, Sara
dc.contributor.authorRodriguez Antona, Cristina 
dc.contributor.authorCascon Soriano, Alberto 
dc.contributor.authorCalsina, Bruna 
dc.contributor.authorMontero-Conde, Cristina 
dc.contributor.authorRobledo Mercedes, Robledo Mercedes 
dc.date.accessioned2020-11-16T10:30:21Z
dc.date.available2020-11-16T10:30:21Z
dc.date.issued2020-07-02
dc.identifier.citationJ Clin Med. 2020;9(7):2082.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11347
dc.description.abstractSpecific genetic variants in the mitochondrially encoded 12S ribosomal RNA gene (MT-RNR1) cause aminoglycoside-induced irreversible hearing loss. Mitochondrial DNA is usually not included in targeted sequencing experiments; however, off-target data may deliver this information. Here, we extract MT-RNR1 genetic variation, including the most relevant ototoxicity variant m.1555A>G, using the off-target reads of 473 research samples, sequenced through a capture-based, custom-targeted panel and whole exome sequencing (WES), and of 1245 diagnostic samples with clinical WES. Sanger sequencing and fluorescence-based genotyping were used for genotype validation. There was a correlation between off-target reads and mitochondrial coverage (rcustomPanel = 0.39, p = 2 × 10-13 and rWES = 0.67, p = 7 × 10-21). The median read depth of MT-RNR1 m.1555 was similar to the average mitochondrial genome coverage, with saliva and blood samples giving comparable results. The genotypes from 415 samples, including three m.1555G carriers, were concordant with fluorescence-based genotyping data. In clinical WES, median MT-RNR1 coverage was 56×, with 90% of samples having ≥20 reads at m.1555 position, and one m.1494T and three m.1555G carriers were identified with no evidence for heteroplasmy. Altogether, this study shows that obtaining MT-RNR1 genotypes through off-target reads is an efficient strategy that can impulse preemptive pharmacogenetic screening of this mitochondrial gene.es_ES
dc.description.sponsorshipThis work was supported by the project RTI2018-095039-B-I00 (MCI/AEI/FEDER, EU) and "la Caixa Foundation" INPhiNIT Retaining Doctorate Fellowship Programme (LCF/BQ/DR19/11740015).es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectRIBOSOMAL-RNA GENEes_ES
dc.subjectMITOCHONDRIAL 1555A-GREATER-THAN-G MUTATION;es_ES
dc.subjectHEARING-LOSSes_ES
dc.subjectSUSCEPTIBILITYes_ES
dc.subjectDNAes_ES
dc.subjectPREVALENCEes_ES
dc.subjectHETEROPLASMYes_ES
dc.subjectPHENOTYPESes_ES
dc.subjectEXOMEes_ES
dc.titleA Novel Approach for the Identification of Pharmacogenetic Variants in MT-RNR1 through Next-Generation Sequencing Off-Target Data.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID32630724es_ES
dc.format.volume9es_ES
dc.format.number7es_ES
dc.identifier.doi10.3390/jcm9072082es_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderFundación La Caixaes_ES
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.3390/jcm9072082es_ES
dc.identifier.journalJournal of clinical medicinees_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Cáncer Endocrino Hereditarioes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/LCF/BQ/DR19/11740015es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/RTI2018-095039-B-I00es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Thumbnail
Acceso Abierto
Acceso Abierto
Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional