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dc.contributor.authorShearer, Aiden Eliot
dc.contributor.authorEppsteiner, Robert W.
dc.contributor.authorBooth, Kevin T.
dc.contributor.authorEphraim, Sean S.
dc.contributor.authorGurrola, Jose, II
dc.contributor.authorSimpson, Allen
dc.contributor.authorBlack-Ziegelbein, E. Ann
dc.contributor.authorJoshi, Swati
dc.contributor.authorRavi, Harini
dc.contributor.authorGiuffre, Angelica C.
dc.contributor.authorHappe, Scott
dc.contributor.authorHildebrand, Michael S.
dc.contributor.authorAzaiez, Hela
dc.contributor.authorBayazıt, Yıldırım Ahmet
dc.contributor.authorErdal, Mehmet Emin
dc.contributor.authorLopez-Escamez, Jose Antonio
dc.contributor.authorGazquez, Irene
dc.contributor.authorTamayo, Marta L.
dc.contributor.authorGelvez, Nancy Yaneth
dc.contributor.authorLeal, Greizy Lopez
dc.contributor.authorJalas, Chaim
dc.contributor.authorEkstein, Josef
dc.contributor.authorYang, Tao
dc.contributor.authorUsami, Shin-ichi
dc.contributor.authorKahrizi, Kimia
dc.contributor.authorBazazzadegan, Niloofar
dc.contributor.authorNajmabadi, Hossein
dc.contributor.authorScheetz, Todd E.
dc.contributor.authorBraun, Terry A.
dc.contributor.authorCasavant, Thomas L.
dc.contributor.authorLeProust, Emily M.
dc.contributor.authorSmith, Richard J. H.
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:35:23Z
dc.date.available10.07.201910:49:14
dc.date.available2019-07-10T19:35:23Z
dc.date.issued2014en_US
dc.identifier.citationShearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., Simpson, A., Black-Ziegelbein, E. A. ... Smith, R. J. H. (2014). Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. American Journal of Human Genetics, 95(4), 445-453. https://dx.doi.org/10.1016/j.ajhg.2014.09.001en_US
dc.identifier.issn0002-9297
dc.identifier.urihttps://hdl.handle.net/20.500.12511/750
dc.identifier.urihttps://dx.doi.org/10.1016/j.ajhg.2014.09.001
dc.description.abstractEthnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) >0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.en_US
dc.language.isoengen_US
dc.publisherCell Pressen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEthnic-Specific Differencesen_US
dc.subjectMinor Allele Frequencyen_US
dc.subjectPathogenic Deafness Variantsen_US
dc.titleUtilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variantsen_US
dc.typearticleen_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Kulak Burun Boğaz Hastalıkları Ana Bilim Dalıen_US
dc.identifier.volume95en_US
dc.identifier.issue4en_US
dc.identifier.startpage445en_US
dc.identifier.endpage453en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1016/j.ajhg.2014.09.001en_US
dc.identifier.wosqualityQ1en_US
dc.identifier.scopusqualityQ1en_US


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