Elusive copy number variation in the mouse genome.
Elusive copy number variation in the mouse genome.
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DOI：
10.1371/journal.pone.0012839
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发表时间：
2010-09-21
期刊：
影响因子：
3.7
通讯作者：
Mott R
中科院分区：
文献类型：
--
作者：
Agam A;Yalcin B;Bhomra A;Cubin M;Webber C;Holmes C;Flint J;Mott R
阵列比较基因组杂交（aCGH）检测哺乳动物基因组中的拷贝数变异（CNVs），使人们越来越意识到这类序列变异作为表型变异的原因的潜在重要性。然而，研究之间存在很大差异，因此基因组受CNVs影响的程度尚不清楚。我们结合近交系小鼠CNVs的分子和aCGH分析来探讨这个问题。使用210万个探针阵列，我们在7个近交小鼠品系中鉴定出1,477个缺失和499个增益。分子表征表明，该阵列检测到的cnv中约有三分之一是假阳性，我们估计假阴性率超过50%。我们表明，研究之间的低一致性主要是由于CNVs的分子性质，其中许多CNVs由一系列较小的缺失和增益组成，这些缺失和增益散布在DNA拷贝数正常的区域。我们的研究结果表明，通过阵列检测到的cnv可能是较小的cnv的巧合共定位，其存在比孤立的小拷贝数改变更有可能扰乱aCGH杂交谱。我们的发现有助于解释迄今为止未探索的基于阵列的小鼠基因组拷贝数变异研究之间的差异。
Array comparative genomic hybridization (aCGH) to detect copy number variants (CNVs) in mammalian genomes has led to a growing awareness of the potential importance of this category of sequence variation as a cause of phenotypic variation. Yet there are large discrepancies between studies, so that the extent of the genome affected by CNVs is unknown. We combined molecular and aCGH analyses of CNVs in inbred mouse strains to investigate this question. Using a 2.1 million probe array we identified 1,477 deletions and 499 gains in 7 inbred mouse strains. Molecular characterization indicated that approximately one third of the CNVs detected by the array were false positives and we estimate the false negative rate to be more than 50%. We show that low concordance between studies is largely due to the molecular nature of CNVs, many of which consist of a series of smaller deletions and gains interspersed by regions where the DNA copy number is normal. Our results indicate that CNVs detected by arrays may be the coincidental co-localization of smaller CNVs, whose presence is more likely to perturb an aCGH hybridization profile than the effect of an isolated, small, copy number alteration. Our findings help explain the hitherto unexplored discrepancies between array-based studies of copy number variation in the mouse genome.
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