The fine-scale and complex architecture of human copy-number variation
The fine-scale and complex architecture of human copy-number variation
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DOI：
10.1016/j.ajhg.2007.12.010
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发表时间：
2008-03-01
影响因子：
9.8
通讯作者：
Lee, Charles
中科院分区：
文献类型：
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作者：
Perry, George H.;Ben-Dor, Amir;Lee, Charles
尽管对拷贝数变异（CNVs）的潜在功能意义相当兴奋，但我们仍然缺乏对人类基因组中绝大多数CNV区域的精细结构的了解。在这项研究中，我们使用了一个高分辨率的基于阵列的比较基因组杂交（aCGH）平台，以约1 kb的分辨率靶向人类基因组的已知CNV区域，以询问来自4个HapMap群体的30个个体的基因组DNA。我们的研究结果显示，1153个CNV位点中有1020个（88%）实际上比基于先前发表的研究的基因组变异数据库中记录的大小更小。在876个CNV区域（76%）中观察到超过50%的尺寸减小。我们的结论是，目前已知的常见人类CNVs的总基因组含量可能比以前认为的要小。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的复杂性，其形式为较大的CNV中的较小的CNV和断裂点具有个体间变异的CNV。未来的关联研究旨在捕捉CNVs对疾病表型的潜在影响，将需要考虑如何最好地确定这种以前未表征的复杂性。
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.