David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 76-561, 500 Main Street, Cambridge, MA 02139, USA.
Cell. 2013 Jan 31;152(3):394-405. doi: 10.1016/j.cell.2012.11.043.
Changes in DNA copy number, whether confined to specific genes or affecting whole chromosomes, have been identified as causes of diseases and developmental abnormalities and as sources of adaptive potential. Here, we discuss the costs and benefits of DNA copy-number alterations. Changes in DNA copy number are largely detrimental. Amplifications or deletions of specific genes can elicit discrete defects. Large-scale changes in DNA copy number can also cause detrimental phenotypes that are due to the cumulative effects of copy-number alterations of many genes simultaneously. On the other hand, studies in microorganisms show that DNA copy-number alterations can be beneficial, increasing survival under selective pressure. As DNA copy-number alterations underlie many human diseases, we will end with a discussion of gene copy-number changes as therapeutic targets.
DNA 拷贝数的变化，无论是局限于特定基因还是影响整个染色体，都已被确定为疾病和发育异常的原因，也是适应潜力的来源。在这里，我们讨论 DNA 拷贝数改变的成本和收益。DNA 拷贝数的变化在很大程度上是有害的。特定基因的扩增或缺失会引起离散的缺陷。大规模的 DNA 拷贝数变化也会导致有害的表型，这是由于许多基因同时发生拷贝数改变的累积效应。另一方面，微生物的研究表明，DNA 拷贝数的改变可能是有益的，能提高在选择压力下的生存能力。由于 DNA 拷贝数的改变是许多人类疾病的基础，我们将以讨论基因拷贝数改变作为治疗靶点作为结束。
