拷贝数变异:基因组多样性的新形式

Copy-number variation:a new pattern of structural diversity in genome

基因拷贝数变异是指DNA片段大小范围从kb到Mb的亚微观突变,是一可能具有致病性、良性或未知临床意义的基因组改变。Fosmid末端配对序列比较策略、比较基因组杂交芯片是当前较多使用的检测手段。染色体非等位的同源重排、非同源突变和非βDNA结构是造成基因组拷贝数变异的重要原因。拷贝数变异可导致不同程度的基因表达差异,对正常表型的构成及疾病的发生发展具有一定作用。文章在总结基因拷贝数变异的认识过程和研究策略的基础上,分析了拷贝数变异的形成和作用机制,介绍了第一代人类基因组拷贝数变异图谱,阐述了拷贝数变异研究的临床意义,提示在探索疾病相关的遗传变异时不能错失拷贝数变异这一基因组多样性的新形式。

Copy number variation （CNV） is increasingly recognized as a source of inter-individual differences in genome sequence and has been proposed as a driving force for genome evolution and phenotypic variation. Many CNVs resulted in different levels of gene expression, which may account for a significant proportion of normal phenotypic variation and human diseases. This review unveiled the research process and study strategy of CNVs. Subsequently, the potential mechanisms of CNV formation and its clinical implications were discussed. In addition, the first-generation copy number variation map of the human genome was introduced, which demonstrated that DNA copy number variation was associated with specific chromosomal rearrangements and genomic disorders.