Center for Human Disease Modeling, Duke University, Durham 27710, USA.
Curr Opin Genet Dev. 2013 Jun;23(3):240-8. doi: 10.1016/j.gde.2013.04.013. Epub 2013 Jun 5.
Copy number variants (CNVs) represent a frequent type of lesion in human genetic disorders that typically affects numerous genes simultaneously. This has raised the challenge of understanding which genes within a CNV drive clinical phenotypes. Although CNVs can arise by multiple mechanisms, a subset is driven by local genomic architecture permissive to recombination events that can lead to both deletions and duplications. Phenotypic analyses of patients with such reciprocal CNVs have revealed instances in which the phenotype is either identical or mirrored; strikingly, molecular studies have shown that such phenotypes are often driven by reciprocal dosage defects of the same transcript. Here we explore how these observations can help the dissection of CNVs and inform the genetic architecture of CNV-induced disorders.
拷贝数变异（CNVs）是人类遗传疾病中常见的病变类型，通常会同时影响多个基因。这就提出了一个挑战，即需要了解 CNV 中哪些基因会导致临床表型。虽然 CNVs 可以通过多种机制产生，但其中一部分是由局部基因组结构驱动的，这些结构有利于重组事件的发生，从而导致缺失和重复。对具有这种相互 CNV 的患者进行的表型分析揭示了这样一种情况，即表型要么完全相同，要么完全相反；引人注目的是，分子研究表明，这种表型通常是由同一转录物的相互剂量缺陷所驱动的。在这里，我们探讨这些观察结果如何帮助我们解析 CNV，并为 CNV 诱导疾病的遗传结构提供信息。
