Genetics Core, Nestlé Institute of Health Sciences Lausanne, Switzerland.
Front Genet. 2013 May 30;4:92. doi: 10.3389/fgene.2013.00092. eCollection 2013.
Differences between genomes can be due to single nucleotide variants, translocations, inversions, and copy number variants (CNVs, gain or loss of DNA). The latter can range from sub-microscopic events to complete chromosomal aneuploidies. Small CNVs are often benign but those larger than 500 kb are strongly associated with morbid consequences such as developmental disorders and cancer. Detecting CNVs within and between populations is essential to better understand the plasticity of our genome and to elucidate its possible contribution to disease. Hence there is a need for better-tailored and more robust tools for the detection and genome-wide analyses of CNVs. While a link between a given CNV and a disease may have often been established, the relative CNV contribution to disease progression and impact on drug response is not necessarily understood. In this review we discuss the progress, challenges, and limitations that occur at different stages of CNV analysis from the detection (using DNA microarrays and next-generation sequencing) and identification of recurrent CNVs to the association with phenotypes. We emphasize the importance of germline CNVs and propose strategies to aid clinicians to better interpret structural variations and assess their clinical implications.
基因组之间的差异可能是由于单核苷酸变异、易位、倒位和拷贝数变异（CNVs，DNA 的增益或丢失）引起的。后者的范围可以从亚微观事件到完全的染色体非整倍体。小的 CNVs 通常是良性的，但大于 500kb 的 CNVs 则与发育障碍和癌症等严重后果密切相关。在人群内部和之间检测 CNVs 对于更好地理解我们基因组的可塑性以及阐明其对疾病的可能贡献至关重要。因此，需要更好地针对 CNVs 进行定制和更强大的检测和全基因组分析工具。虽然已经确定了特定 CNV 与疾病之间的联系，但相对于疾病进展和药物反应的 CNV 贡献并不一定被理解。在这篇综述中，我们讨论了在从 DNA 微阵列和下一代测序的检测和识别到与表型的关联的 CNV 分析的不同阶段所出现的进展、挑战和局限性。我们强调了种系 CNVs 的重要性，并提出了一些策略来帮助临床医生更好地解释结构变异，并评估其临床意义。
