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dc.contributor.authorKukurba, Kimberly R.en_US
dc.contributor.authorZhang, Ruien_US
dc.contributor.authorLi, Xinen_US
dc.contributor.authorSmith, Kevin S.en_US
dc.contributor.authorKnowles, David A.en_US
dc.contributor.authorHow Tan, Mengen_US
dc.contributor.authorPiskol, Roberten_US
dc.contributor.authorLek, Monkolen_US
dc.contributor.authorSnyder, Michaelen_US
dc.contributor.authorMacArthur, Daniel G.en_US
dc.contributor.authorLi, Jin Billyen_US
dc.contributor.authorMontgomery, Stephen B.en_US
dc.date.accessioned2014-07-07T18:15:06Z
dc.date.issued2014en_US
dc.identifier.citationKukurba, K. R., R. Zhang, X. Li, K. S. Smith, D. A. Knowles, M. How Tan, R. Piskol, et al. 2014. “Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues.” PLoS Genetics 10 (5): e1004304. doi:10.1371/journal.pgen.1004304. http://dx.doi.org/10.1371/journal.pgen.1004304.en
dc.identifier.issn1553-7390en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12407031
dc.description.abstractPersonal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pgen.1004304en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006732/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectComputational Biologyen
dc.subjectGenome Analysisen
dc.subjectTranscriptome Analysisen
dc.subjectGenome Expression Analysisen
dc.subjectGeneticsen
dc.subjectGenomicsen
dc.subjectFunctional Genomicsen
dc.subjectGene Expressionen
dc.subjectMolecular Biologyen
dc.subjectMolecular Biology Techniquesen
dc.subjectSequencing Techniquesen
dc.subjectGenome Sequencingen
dc.titleAllelic Expression of Deleterious Protein-Coding Variants across Human Tissuesen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Geneticsen
dash.depositing.authorLek, Monkolen_US
dc.date.available2014-07-07T18:15:06Z
dc.identifier.doi10.1371/journal.pgen.1004304*
dash.authorsorderedfalse
dash.contributor.affiliatedMacArthur, Daniel
dash.contributor.affiliatedLek, Monkol


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