Silent (Synonymous) SNPs: Should We Care About Them?

  • Ryan Hunt
  • Zuben E. Sauna
  • Suresh V. Ambudkar
  • Michael M. Gottesman
  • Chava Kimchi-Sarfaty
Part of the Methods in Molecular Biology™ book series (MIMB, volume 578)


One of the surprising findings of the Human Genome Project was that single nucleotide polymorphisms (SNPs), which, by definition, have a minor allele frequency greater than 1%, occur at higher rates than previously suspected. When occurring in the gene coding regions, SNPs can be synonymous (i.e., not causing a change in the amino acid) or nonsynonymous (when the amino acid is altered). It has long been assumed that synonymous SNPs are inconsequential, as the primary sequence of the protein is retained. A number of studies have questioned this assumption over the last decade, showing that synonymous mutations are also under evolutionary pressure and they can be implicated in disease. More importantly, several of the mechanisms by which synonymous mutations alter the structure, function, and expression level of proteins are now being elucidated. Studies have demonstrated that synonymous polymorphisms can affect messenger RNA splicing, stability, and structure as well as protein folding. These changes can have a significant effect on the function of proteins, change cellular response to therapeutic targets, and often explain the different responses of individual patients to a certain medication.

Key words

Single nucleotide polymorphism messenger RNA splicing messenger RNA stability messenger RNA structure protein folding synonymous mutations nonsynonymous mutations codon frequency codon usage 



This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Special thanks are expressed to George Leiman, NCI, NIH, and Geetha S., CBER, FDA, for editorial assistance.


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2003 2009

Authors and Affiliations

  • Ryan Hunt
    • 1
  • Zuben E. Sauna
    • 1
  • Suresh V. Ambudkar
    • 2
  • Michael M. Gottesman
    • 2
  • Chava Kimchi-Sarfaty
    • 1
  1. 1.Laboratory of Hemostasis, Division of HematologyCenter for Biologics Evaluation and Research, Food and Drug AdministrationBethesdaUSA
  2. 2.Laboratory of Cell BiologyNational Cancer Institute, National Institutes of HealthBethesdaUSA

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