Mikhail Fady M
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Curr Opin Pediatr. 2014 Dec;26(6):646-52. doi: 10.1097/MOP.0000000000000142.
Recent studies clearly demonstrate that copy number variations (CNVs) are widespread in our genome and play an important role in human genetic variation, accounting for both human population diversity and human genetic disease. This review will discuss the most current knowledge regarding our understanding of the biology of CNVs in relation to human genetic disease.
CNVs associated with human genetic disease can be either recurrent, with a common size and breakpoint clustering, or nonrecurrent, with different sizes and variable breakpoints. Two types of recurrent CNVs have been distinguished, including the syndromic forms in which the phenotypic features are relatively consistent, and those in which the same recurrent CNV can be associated with a diverse set of diagnoses. Recently, the 'Two-hit model' was used to explain the phenotypic variability associated with the latter group of recurrent CNVs. Nonrecurrent CNVs, on the contrary, occur at a relatively lower frequency at the individual locus level but collectively they are as common as recurrent CNVs. Finally, the study of CNV burden in different diseases demonstrated a clear trend of an increasing CNV burden in diseases with more severe phenotypes.
In spite of the advances in the study of the CNV landscape associated with human genetic disease, there still remain many unexplored questions especially regarding the role of CNVs in the pathogenesis of complex human genetic diseases.
近期研究清楚地表明，拷贝数变异（CNV）在我们的基因组中广泛存在，并且在人类遗传变异中发挥重要作用，它既解释了人类群体多样性，也与人类遗传疾病相关。本综述将讨论目前有关我们对与人类遗传疾病相关的CNV生物学理解的最新知识。
与人类遗传疾病相关的CNV可以是反复出现的，具有共同的大小和断点聚类，也可以是非反复出现的，具有不同的大小和可变的断点。已区分出两种类型的反复出现的CNV，包括表型特征相对一致的综合征形式，以及相同的反复出现的CNV可与多种诊断相关联的形式。最近，“双打击模型”被用于解释与后一组反复出现的CNV相关的表型变异性。相反，非反复出现的CNV在个体基因座水平上出现的频率相对较低，但总体上它们与反复出现的CNV一样常见。最后，对不同疾病中CNV负担的研究表明，在具有更严重表型的疾病中，CNV负担有明显增加的趋势。
尽管在与人类遗传疾病相关的CNV格局研究方面取得了进展，但仍然存在许多未探索的问题，特别是关于CNV在复杂人类遗传疾病发病机制中的作用。
