Heritability in the efficiency of nonsense-mediated mRNA decay in humans.
AffiliationSchool of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland. Cathal.Seoighe@nuigalway.ie
Expressed Sequence Tags
Genome-Wide Association Study
Oligonucleotide Array Sequence Analysis
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CitationHeritability in the efficiency of nonsense-mediated mRNA decay in humans. 2010, 5 (7):e11657 PLoS ONE
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.
CollectionsJournal articles & published research
- Large-scale evidence for conservation of NMD candidature across mammals.
- Authors: de Lima Morais DA, Harrison PM
- Issue date: 2010 Jul 21
- Detection and analysis of alternative splicing in Yarrowia lipolytica reveal structural constraints facilitating nonsense-mediated decay of intron-retaining transcripts.
- Authors: Mekouar M, Blanc-Lenfle I, Ozanne C, Da Silva C, Cruaud C, Wincker P, Gaillardin C, Neuvéglise C
- Issue date: 2010
- UPF1, a conserved nonsense-mediated mRNA decay factor, regulates cyst wall protein transcripts in Giardia lamblia.
- Authors: Chen YH, Su LH, Huang YC, Wang YT, Kao YY, Sun CH
- Issue date: 2008
- Nonsense-mediated mRNA decay (NMD) silences the accumulation of aberrant trypsin proteinase inhibitor mRNA in Nicotiana attenuata.
- Authors: Wu J, Kang JH, Hettenhausen C, Baldwin IT
- Issue date: 2007 Aug
- Comparison of nonsense-mediated mRNA decay efficiency in various murine tissues.
- Authors: Zetoune AB, Fontanière S, Magnin D, Anczuków O, Buisson M, Zhang CX, Mazoyer S
- Issue date: 2008 Dec 5