Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping.
Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping.
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DOI：
10.1093/nar/gkn122
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发表时间：
2008-06
影响因子：
14.9
通讯作者：
Lengauer T
中科院分区：
文献类型：
--
作者：
Bock C;Walter J;Paulsen M;Lengauer T
基因组DNA甲基化谱在人群中表现出很大的差异，对基因调控具有重要的功能意义。到目前为止，对健康个体中DNA甲基化变异的特征和决定因素知之甚少。我们对来自多个个体的高分辨率甲基化图谱进行了生物信息学分析，揭示了与局部DNA序列密切相关的个体间变异的复杂模式。在所有个体中，富含CpG的区域表现出较低且相对相似的DNA甲基化水平，但在（许多）未甲基化的CpG中，（少数）甲基化的顺序在个体之间随机不同。相比之下，CpG缺失区域表现出显著升高的个体间变异水平，但也表现出不相关个体之间特异性DNA甲基化模式的显著保守性。这一观察结果对DNA甲基化的实验分析具有重要意义，例如在表观基因组计划的背景下。首先，单CpG分辨率的DNA甲基化图谱有望揭示人类基因组中CpG贫乏的大部分的信息性DNA甲基化模式。其次，对于富含CpG的区域，测量平均甲基化水平而不是测定每个单个CpG就足够了。我们证实了这些结论，在硅片基准研究的六个广泛使用的DNA甲基化定位方法。基于我们的研究结果，我们提出了一个成本优化的双轨战略哺乳动物甲基化组项目。
Genomic DNA methylation profiles exhibit substantial variation within the human population, with important functional implications for gene regulation. So far little is known about the characteristics and determinants of DNA methylation variation among healthy individuals. We performed bioinformatic analysis of high-resolution methylation profiles from multiple individuals, uncovering complex patterns of inter-individual variation that are strongly correlated with the local DNA sequence. CpG-rich regions exhibit low and relatively similar levels of DNA methylation in all individuals, but the sequential order of the (few) methylated among the (many) unmethylated CpGs differs randomly across individuals. In contrast, CpG-poor regions exhibit substantially elevated levels of inter-individual variation, but also significant conservation of specific DNA methylation patterns between unrelated individuals. This observation has important implications for experimental analysis of DNA methylation, e.g. in the context of epigenome projects. First, DNA methylation mapping at single-CpG resolution is expected to uncover informative DNA methylation patterns for the CpG-poor bulk of the human genome. Second, for CpG-rich regions it will be sufficient to measure average methylation levels rather than assaying every single CpG. We substantiate these conclusions by an in silico benchmarking study of six widely used methods for DNA methylation mapping. Based on our findings, we propose a cost-optimized two-track strategy for mammalian methylome projects.
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影响因子：
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