Perry George H, Ben-Dor Amir, Tsalenko Anya, Sampas Nick, Rodriguez-Revenga Laia, Tran Charles W, Scheffer Alicia, Steinfeld Israel, Tsang Peter, Yamada N Alice, Park Han Soo, Kim Jong-Il, Seo Jeong-Sun, Yakhini Zohar, Laderman Stephen, Bruhn Laurakay, Lee Charles
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Am J Hum Genet. 2008 Mar;82(3):685-95. doi: 10.1016/j.ajhg.2007.12.010. Epub 2008 Jan 24.
Despite considerable excitement over the potential functional significance of copy-number variants (CNVs), we still lack knowledge of the fine-scale architecture of the large majority of CNV regions in the human genome. In this study, we used a high-resolution array-based comparative genomic hybridization (aCGH) platform that targeted known CNV regions of the human genome at approximately 1 kb resolution to interrogate the genomic DNAs of 30 individuals from four HapMap populations. Our results revealed that 1020 of 1153 CNV loci (88%) were actually smaller in size than what is recorded in the Database of Genomic Variants based on previously published studies. A reduction in size of more than 50% was observed for 876 CNV regions (76%). We conclude that the total genomic content of currently known common human CNVs is likely smaller than previously thought. In addition, approximately 8% of the CNV regions observed in multiple individuals exhibited genomic architectural complexity in the form of smaller CNVs within larger ones and CNVs with interindividual variation in breakpoints. Future association studies that aim to capture the potential influences of CNVs on disease phenotypes will need to consider how to best ascertain this previously uncharacterized complexity.
尽管人们对拷贝数变异（CNV）的潜在功能意义极为兴奋，但我们对人类基因组中绝大多数CNV区域的精细结构仍缺乏了解。在本研究中，我们使用了基于高分辨率阵列的比较基因组杂交（aCGH）平台，该平台以约1 kb的分辨率靶向人类基因组的已知CNV区域，以检测来自四个HapMap群体的30个个体的基因组DNA。我们的结果显示，基于先前发表的研究，1153个CNV位点中的1020个（88%）实际大小比基因组变异数据库中记录的要小。876个CNV区域（76%）观察到大小减少超过50%。我们得出结论，目前已知的常见人类CNV的总基因组含量可能比之前认为的要小。此外，在多个个体中观察到的约8%的CNV区域表现出基因组结构复杂性，形式为较大CNV内存在较小的CNV以及个体间断点存在变异的CNV。旨在捕捉CNV对疾病表型潜在影响的未来关联研究将需要考虑如何最好地确定这种先前未被表征的复杂性。
