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Gene expression as a quantitative trait: what about translation?
  1. Constantin Polychronakos
  1. Correspondence to Dr Constantin Polychronakos, The Endocrine Genetics Laboratory, Departments of Pediatrics and Human Genetics, the Research Institute of the McGill University Health Centre, The Montreal Children's Hospital, 2300 Tupper, suite C244, Montréal, Québec H3H1P3, Canada; Constantin.Polychronakos{at}


Background and objective Much progress has been made in determining loci where gene expression at the steady-state mRNA level is controlled by genetic variants in cis. However, mRNA is only a proxy for what matters in phenotypic variation, which is protein level. We set out to review the evidence for exonic polymorphisms that affect translation of mRNA.

Methods Informal literature review.

Results There is ample literature on monogenic diseases caused by rare mutations in translationally active mRNA elements. Such mutations may eliminate or create AUG initiation codons or alter the Kozak sequences surrounding them, alter RNA secondary structure, destroy or enhance internal ribosomal entry sequences or Fe-response elements. By contrast, examples of complex phenotypes determined by common polymorphisms in these elements are scarce, although reports (to be confirmed) of functionally polymorphic miRNA binding sites are beginning to appear.

Conclusions Given the methodological limitations of detecting these translational effects, we posit that existing knowledge of such effects in common complex phenotypes represent the ‘tip of the iceberg’. High-throughput quantitative proteomics is beginning to offer a promise to explore this possibility.

  • Complex traits
  • Critical appraisal literature
  • MicroRNA
  • Molecular genetics
  • Proteomics

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