Heritability in the efficiency of nonsense-mediated mRNA decay in humans

dc.contributor.authorSeoighe, Cathalen_ZA
dc.contributor.authorGehring, Chrisen_ZA
dc.date.accessioned2016-01-02T05:05:50Z
dc.date.available2016-01-02T05:05:50Z
dc.date.issued2010en_ZA
dc.description.abstractBACKGROUND: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. Principal FINDINGS: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. CONCLUSIONS: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3.en_ZA
dc.identifier.apacitationSeoighe, C., & Gehring, C. (2010). Heritability in the efficiency of nonsense-mediated mRNA decay in humans. <i>PLoS One</i>, http://hdl.handle.net/11427/16166en_ZA
dc.identifier.chicagocitationSeoighe, Cathal, and Chris Gehring "Heritability in the efficiency of nonsense-mediated mRNA decay in humans." <i>PLoS One</i> (2010) http://hdl.handle.net/11427/16166en_ZA
dc.identifier.citationSeoighe, C., & Gehring, C. (2010). Heritability in the efficiency of nonsense-mediated mRNA decay in humans. PloS one, 5(7), e11657. doi:10.1371/journal.pone.0011657en_ZA
dc.identifier.ris TY - Journal Article AU - Seoighe, Cathal AU - Gehring, Chris AB - BACKGROUND: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. Principal FINDINGS: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. CONCLUSIONS: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3. DA - 2010 DB - OpenUCT DO - 10.1371/journal.pone.0011657 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Heritability in the efficiency of nonsense-mediated mRNA decay in humans TI - Heritability in the efficiency of nonsense-mediated mRNA decay in humans UR - http://hdl.handle.net/11427/16166 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16166
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0011657
dc.identifier.vancouvercitationSeoighe C, Gehring C. Heritability in the efficiency of nonsense-mediated mRNA decay in humans. PLoS One. 2010; http://hdl.handle.net/11427/16166.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2010 Seoighe, Gehringen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherIntronsen_ZA
dc.subject.otherMessenger RNAen_ZA
dc.subject.otherMicroarraysen_ZA
dc.subject.otherPseudogenesen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherPhenotypesen_ZA
dc.subject.otherAlternative splicingen_ZA
dc.subject.otherTranscriptome analysisen_ZA
dc.titleHeritability in the efficiency of nonsense-mediated mRNA decay in humansen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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