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

 

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dc.contributor.author Seoighe, Cathal en_ZA
dc.contributor.author Gehring, Chris en_ZA
dc.date.accessioned 2016-01-02T05:05:50Z
dc.date.available 2016-01-02T05:05:50Z
dc.date.issued 2010 en_ZA
dc.identifier.citation Seoighe, 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.0011657 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16166
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0011657
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Introns en_ZA
dc.subject.other Messenger RNA en_ZA
dc.subject.other Microarrays en_ZA
dc.subject.other Pseudogenes en_ZA
dc.subject.other Gene expression en_ZA
dc.subject.other Phenotypes en_ZA
dc.subject.other Alternative splicing en_ZA
dc.subject.other Transcriptome analysis en_ZA
dc.title Heritability in the efficiency of nonsense-mediated mRNA decay in humans en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2010 Seoighe, Gehring en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
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This 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. Except where otherwise noted, this item's license is described as This 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.