Gene dosage imbalances: action, reaction, and models

Trends Biochem Sci. 2015 Jun;40(6):309-17. doi: 10.1016/j.tibs.2015.03.011. Epub 2015 Apr 27.


Single-gene deletions, duplications, and misregulation, as well as aneuploidy, can lead to stoichiometric imbalances within macromolecular complexes and cellular networks, causing their malfunction. Such alterations can be responsible for inherited or somatic genetic disorders including Mendelian diseases, aneuploid syndromes, and cancer. We review the effects of gene dosage alterations at the transcriptomic and proteomic levels, and the various responses of the cell to counteract their effects. Furthermore, we explore several biochemical models and ideas that can provide the rationale for treatments modulating the effects of gene dosage imbalances.

Keywords: aneuploidy; buffering; compensation; deletion; dosage balance; duplication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneuploidy*
  • Gene Dosage / genetics*
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Models, Genetic
  • Mutation
  • Neoplasms / genetics*
  • Proteomics