Dhawan Dipali, Padh Harish
BV Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej-Gandhinagar Highway, Thaltej, Ahmedabad, 380 054, Gujarat, India.
Curr Opin Mol Ther. 2009 Dec;11(6):670-80.
The human genome is characterized by structural variations, in addition to having expansive areas of tandem repeat sequences and SNPs. Copy number variations (CNVs) in the human genome are the result of insertions, deletions, duplications and complex multisite variants, affecting approximately 10 to 12% of the genome and covering a higher number of nucleotides than SNPs. Several methods are used for the detection of CNVs, including approaches based on hybridization, such as arrays, PCR amplification, FRET and sequencing. These methods can identify microscopic structural variations (> or = 3 Mb in size), as well as submicroscopic structural variations (approximately 1 kb to 3 Mb in size). CNVs can affect drug metabolism and disease susceptibility. Therefore, the effect of variations in the copies of genes on the efficacy and toxicity of therapeutic agents needs to be well established at both pharmacokinetic and pharmacodynamic levels prior to the use of these agents clinically. This review evaluates the techniques for detecting the CNVs available at the time of publication, citing examples from the application of CNVs in clinical pharmacogenetics.
人类基因组除了具有大片段串联重复序列和单核苷酸多态性（SNP）外，还具有结构变异特征。人类基因组中的拷贝数变异（CNV）是插入、缺失、重复和复杂多位点变异的结果，约占基因组的10%至12%，覆盖的核苷酸数量比SNP更多。检测CNV的方法有多种，包括基于杂交的方法，如阵列、聚合酶链反应（PCR）扩增、荧光共振能量转移（FRET）和测序。这些方法可以识别微观结构变异（大小≥3兆碱基）以及亚微观结构变异（大小约为1千碱基至3兆碱基）。CNV可影响药物代谢和疾病易感性。因此，在临床使用这些药物之前，需要在药代动力学和药效学水平上充分确定基因拷贝数变异对治疗药物疗效和毒性的影响。本综述评估了发表时可用的检测CNV的技术，并引用了CNV在临床药物遗传学中的应用实例。
