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Li Q, Makri A, Lu Y, et al. Genome-wide search for exonic variants affecting translational efficiency. Nat Commun. 2013;4:2260doi: 10.1038/ncomms3260.
Li, Q., Makri, A., Lu, Y., Marchand, L., Grabs, R., Rousseau, M., Ounissi-Benkalha, H., Pelletier, J., Robert, F., Harmsen, E., Hudson, T. J., Pastinen, T., Polychronakos, C., & Qu, H. Q. (2013). Genome-wide search for exonic variants affecting translational efficiency. Nature communications, 42260. https://doi.org/10.1038/ncomms3260
Li, Quan, et al. "Genome-wide search for exonic variants affecting translational efficiency." Nature communications vol. 4 (2013): 2260. doi: https://doi.org/10.1038/ncomms3260
Li Q, Makri A, Lu Y, Marchand L, Grabs R, Rousseau M, Ounissi-Benkalha H, Pelletier J, Robert F, Harmsen E, Hudson TJ, Pastinen T, Polychronakos C, Qu HQ. Genome-wide search for exonic variants affecting translational efficiency. Nat Commun. 2013;4:2260. doi: 10.1038/ncomms3260. PMID: 23900168; PMCID: PMC3749366.
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Nat Commun. 2013;4:2260. doi: 10.1038/ncomms3260.

Genome-wide search for exonic variants affecting translational efficiency.

Nature communications

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, Hui-Qi Qu

Affiliations

  1. Endocrine Genetics Laboratory, The McGill University Health Center, Montreal Children's Hospital, Montréal, Québec, Canada.

PMID: 23900168 PMCID: PMC3749366 DOI: 10.1038/ncomms3260

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.

References

  1. Mol Immunol. 2000 Feb-Mar;37(3-4):141-9 - PubMed
  2. PLoS Genet. 2011 Aug;7(8):e1002216 - PubMed
  3. EMBO J. 1985 Feb;4(2):453-6 - PubMed
  4. Nat Genet. 2012 May 06;44(6):676-80 - PubMed
  5. Nature. 2007 Jun 7;447(7145):661-78 - PubMed
  6. Hum Genet. 2006 Aug;120(1):1-21 - PubMed
  7. Nat Genet. 2008 May;40(5):609-15 - PubMed
  8. Nature. 2010 Apr 1;464(7289):768-72 - PubMed
  9. Nat Genet. 2003 Apr;33(4):439-40 - PubMed
  10. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10853-8 - PubMed
  11. Nat Genet. 2009 Jun;41(6):703-7 - PubMed
  12. PLoS Genet. 2011 Jun;7(6):e1001393 - PubMed
  13. Nat Rev Genet. 2013 Jan;14(1):35-48 - PubMed
  14. Cell. 2010 Apr 16;141(2):355-67 - PubMed
  15. Br J Haematol. 1999 Nov;107(2):310-6 - PubMed
  16. Nat Rev Genet. 2009 Mar;10(3):184-94 - PubMed
  17. Nat Genet. 1998 Jan;18(1):49-52 - PubMed
  18. Br J Haematol. 1995 Apr;89(4):900-2 - PubMed
  19. Science. 2006 Dec 22;314(5807):1930-3 - PubMed
  20. Cancer Res. 2010 Apr 15;70(8):3199-208 - PubMed
  21. Diabetes. 2008 Apr;57(4):1143-6 - PubMed
  22. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3319-23 - PubMed
  23. Am J Hum Genet. 2008 Mar;82(3):631-40 - PubMed
  24. Genome Res. 2005 Nov;15(11):1584-91 - PubMed
  25. Nat Genet. 2009 Nov;41(11):1216-22 - PubMed
  26. Nat Genet. 2011 Jul 31;43(9):893-6 - PubMed
  27. J Med Genet. 2012 Sep;49(9):554-7 - PubMed
  28. Diabetes. 2007 Jan;56(1):270-5 - PubMed
  29. Biostatistics. 2009 Apr;10(2):327-34 - PubMed
  30. J Neurosci Res. 2009 Jul;87(9):1953-9 - PubMed
  31. Nat Genet. 2007 Oct;39(10):1217-24 - PubMed
  32. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4324-8 - PubMed
  33. Cell Stem Cell. 2008 May 8;2(5):448-60 - PubMed
  34. Genes Dev. 2005 Jan 1;19(1):104-13 - PubMed
  35. Nucleic Acids Res. 1998 Jul 1;26(13):3097-103 - PubMed
  36. Nat Genet. 2007 Oct;39(10):1202-7 - PubMed
  37. Nat Genet. 2008 Dec;40(12):1399-401 - PubMed
  38. Nat Methods. 2013 Jan;10(1):23 - PubMed
  39. J Cell Biol. 1991 Nov;115(4):887-903 - PubMed
  40. Br J Haematol. 2004 Jan;124(2):224-31 - PubMed
  41. BMC Genomics. 2006 Aug 17;7:213 - PubMed
  42. Biogerontology. 2002;3(1-2):133-6 - PubMed
  43. Genome Med. 2009 Dec 22;1(12):116 - PubMed
  44. Hum Mol Genet. 2005 Dec 15;14(24):3963-71 - PubMed
  45. Nature. 2010 Jul 1;466(7302):113-7 - PubMed
  46. Science. 2009 Sep 4;325(5945):1246-50 - PubMed
  47. Bioinformatics. 2008 Jul 1;24(13):1547-8 - PubMed
  48. Cell. 2010 Apr 16;141(2):227-9 - PubMed
  49. PLoS Biol. 2008 May 6;6(5):e107 - PubMed
  50. Nat Genet. 2007 Jul;39(7):857-64 - PubMed
  51. PLoS Genet. 2005 Dec;1(6):e78 - PubMed
  52. Nat Genet. 1999 Jan;21(1):128-32 - PubMed
  53. Science. 2006 May 12;312(5775):902-6 - PubMed

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