title: Genome-wide search for exonic variants affecting translational efficiency.
abstract: The search for expression quantitative trait loci has traditionally centred entirely on the process of transcription, whereas variants with effects on messenger RNA translation have not been systematically studied. Here we present a high-throughput approach for measuring translational cis-regulation in the human genome. Using ribosomal association as proxy for translational efficiency of polymorphic messenger RNAs, we test the ratio of polysomal/non-polysomal messenger RNA level as a quantitative trait for association with single nucleotide polymorphisms on the same messenger RNA transcript. We identify one important ribosomal distribution effect, from rs1131017 in the 5'-untranslated region of RPS26, that is in high linkage disequilibrium with the 12q13 locus for susceptibility to type 1 diabetes. The effect on translation is confirmed at the protein level by quantitative western blots, both ex vivo and after in vitro translation. Our results are a proof-of-principle that allelic effects on translation can be detected at a transcriptome-wide scale.
authors.affiliation: Endocrine Genetics Laboratory, The McGill University Health Center, Montreal Children's Hospital, Montréal, Québec, Canada.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Angeliki
authors.initials: A
authors.lastname: Makri
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Luc
authors.initials: L
authors.lastname: Marchand
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Grabs
authors.forename: Marylene
authors.initials: M
authors.lastname: Rousseau
authors.forename: Houria
authors.initials: H
authors.lastname: Ounissi-Benkalha
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.forename: Francis
authors.initials: F
authors.lastname: Robert
authors.forename: Eef
authors.initials: E
authors.lastname: Harmsen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
authors.forename: Constantin
authors.initials: C
authors.lastname: Polychronakos
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Qu
mesh_terms: D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005091:Exons / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C489203:RPS26 protein, human; D012269:Ribosomal Proteins
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