复制压力和 CNV 形成的机制。
Replication stress and mechanisms of CNV formation.
机构信息
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, United States.
出版信息
Curr Opin Genet Dev. 2012 Jun;22(3):204-10. doi: 10.1016/j.gde.2012.01.009. Epub 2012 Feb 23.
Abstract
Copy number variants (CNVs) are widely distributed throughout the human genome, where they contribute to genetic variation and phenotypic diversity. De novo CNVs are also a major cause of numerous genetic and developmental disorders. However, unlike many other types of mutations, little is known about the genetic and environmental risk factors for new and deleterious CNVs. DNA replication errors have been implicated in the generation of a major class of CNVs, the nonrecurrent CNVs. We have found that agents that perturb normal replication and create conditions of replication stress, including hydroxyurea and aphidicolin, are potent inducers of nonrecurrent CNVs in cultured human cells. These findings have broad implications for identifying CNV risk factors and for hydroxyurea-related therapies in humans.
摘要
拷贝数变异（CNVs）广泛分布于人类基因组中，它们导致了遗传变异和表型多样性。新生 CNVs 也是许多遗传和发育障碍的主要原因。然而，与许多其他类型的突变不同，人们对新的有害 CNVs 的遗传和环境风险因素知之甚少。DNA 复制错误与一类主要的 CNVs（非重复 CNVs）的产生有关。我们发现，干扰正常复制并产生复制应激条件的试剂，包括羟基脲和阿非迪可林，在培养的人类细胞中能强有力地诱导非重复 CNVs 的产生。这些发现对识别 CNV 风险因素以及人类的羟基脲相关治疗具有广泛的意义。
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