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

Hdl Handle:
http://hdl.handle.net/10147/116369
Title:
Heritability in the efficiency of nonsense-mediated mRNA decay in humans.
Authors:
Seoighe, Cathal; Gehring, Chris
Affiliation:
School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland. Cathal.Seoighe@nuigalway.ie
Citation:
Heritability in the efficiency of nonsense-mediated mRNA decay in humans. 2010, 5 (7):e11657 PLoS ONE
Journal:
PloS one
Issue Date:
2010
URI:
http://hdl.handle.net/10147/116369
DOI:
10.1371/journal.pone.0011657
PubMed ID:
20657766
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.
Language:
en
MeSH:
Codon, Nonsense; Endoribonucleases; Expressed Sequence Tags; Genome-Wide Association Study; Genotype; Humans; Introns; Oligonucleotide Array Sequence Analysis; RNA Stability; Trans-Activators
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorSeoighe, Cathalen
dc.contributor.authorGehring, Chrisen
dc.date.accessioned2010-11-26T10:28:34Z-
dc.date.available2010-11-26T10:28:34Z-
dc.date.issued2010-
dc.identifier.citationHeritability in the efficiency of nonsense-mediated mRNA decay in humans. 2010, 5 (7):e11657 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid20657766-
dc.identifier.doi10.1371/journal.pone.0011657-
dc.identifier.urihttp://hdl.handle.net/10147/116369-
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.-
dc.language.isoenen
dc.subject.meshCodon, Nonsense-
dc.subject.meshEndoribonucleases-
dc.subject.meshExpressed Sequence Tags-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshIntrons-
dc.subject.meshOligonucleotide Array Sequence Analysis-
dc.subject.meshRNA Stability-
dc.subject.meshTrans-Activators-
dc.titleHeritability in the efficiency of nonsense-mediated mRNA decay in humans.en
dc.contributor.departmentSchool of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Galway, Ireland. Cathal.Seoighe@nuigalway.ieen
dc.identifier.journalPloS oneen

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.