Gene dosage imbalances: action, reaction, and models.
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.
Institut Jacques Monod, Paris, France; Université Paris Diderot, Paris, France. Electronic address: veitia.reiner@ijm.univ-paris-diderot.fr.
Reiner A
RA
Veitia
Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Université Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM) and Centre National de la Recherche Scientifique (CNRS) Unités de Recherche U75, U1127, U7225, and Institut du Cerveau et de la Moelle Épinière (ICM), 75013 Paris, France.
Marie Claude
MC
Potier
D000782:Aneuploidy; D018628:Gene Dosage / Q000235:genetics*; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D040901:Proteomics
aneuploidy; buffering; compensation; deletion; dosage balance; duplication