拷贝数变异：基因组多样性的新形式.pdf

HEREDITAS (Beijing) 2009 4 , 31(4): 339―347 ISSN 0253-9772 综述 DOI: 10.3724/SP.J.1005.2009.00339 拷贝数变异: 基因组多样性的新形式 吴志俊, 金玮 , 200025 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β DNA 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。 拷贝数变异; 单核苷酸多态; 国际单倍体计划 Copy-number variation: a new pattern of structural diversity in genome WU Zhi-Jun, JIN Wei Department of Cardiology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China Abstract: 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 hu- man diseases. This review unveiled the research process and study strategy of CNVs. Subsequently, the potential mecha- nisms 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 spe- cific chromosomal rearrangements and genomic disorders. Keywords: copy number variation; single nucleotide polymorphisms; the International HapMap Project 2001 2 , 6 Celera ”2004 , “” [1], , , “”, 2 “ [2, 3] (Copy 收稿日期: 2