Institut Jacques Monod, Paris, France; Université Paris Diderot, Paris, France.
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.
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.
单基因缺失、重复和调控异常，以及非整倍体，可导致大分子复合物和细胞网络内的化学计量失衡，从而导致其功能障碍。这些改变可能导致遗传性或体细胞遗传疾病，包括孟德尔疾病、非整倍体综合征和癌症。我们综述了基因剂量改变在转录组和蛋白质组水平的影响，以及细胞为了抵消这些影响而产生的各种反应。此外，我们还探讨了几种生化模型和思路，这些模型和思路可以为调节基因剂量失衡影响的治疗方法提供依据。
