Genome-wide search for exonic variants affecting translational efficiency

Quan Li, Angeliki Makri, Yang Lu, Luc Marchand, Rosemarie Grabs, Marylene Rousseau, Houria Ounissi-Benkalha, Jerry Pelletier, Francis Robert, Eef Harmsen, Thomas J. Hudson, Tomi Pastinen, Constantin Polychronakos () and Hui-Qi Qu ()
Additional contact information
Quan Li: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Angeliki Makri: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Yang Lu: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Luc Marchand: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Rosemarie Grabs: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Marylene Rousseau: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Houria Ounissi-Benkalha: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Jerry Pelletier: McGill University
Francis Robert: McGill University
Eef Harmsen: McGill University and Genome Québec Innovation Centre
Thomas J. Hudson: McGill University and Genome Québec Innovation Centre
Tomi Pastinen: McGill University and Genome Québec Innovation Centre
Constantin Polychronakos: Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children’s Hospital)
Hui-Qi Qu: Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston, School of Public Health

Nature Communications, 2013, vol. 4, issue 1, 1-6

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3260

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