High quality methylome-wide investigations through next-generation sequencing of DNA from a single archived dry blood spot
High quality methylome-wide investigations through next-generation sequencing of DNA from a single archived dry blood spot
复制标题
DOI：
10.4161/epi.24508
复制
发表时间：
2013-05-01
期刊：
影响因子：
3.7
通讯作者：
van den Oord, Edwin J. C. G.
中科院分区：
文献类型：
--
作者：
Aberg, Karolina A.;Xie, Lin Y.;van den Oord, Edwin J. C. G.
DNA甲基化在复杂疾病的病因学中的潜在重要性已经引起了对旨在询问人类基因组中所有甲基化位点的全甲基化关联研究（MWAS）的发展的兴趣。当使用血液作为MWAS的生物材料时，DNA通常直接从通过静脉穿刺收集的新鲜或冷冻全血中提取。然而，从干血斑提取的DNA也可以是替代的起始材料。在本研究中，我们应用甲基-CpG结合结构域（MBD）蛋白富集技术结合下一代测序（MBD-seq）来评估人类常染色体参考基因组中约2700万个CpG的甲基化状态。我们调查了八个甲基化使用DNA从血斑。将该数据与先前使用来自全血的DNA用相同的MBD-seq方法测定的1，500个甲基化组进行比较。当研究序列质量和生物特征的富集概况时，我们发现从血斑提取的DNA与从全血提取的DNA的结果相当。仅当起始材料的量为
The potential importance of DNA methylation in the etiology of complex diseases has led to interest in the development of methylome-wide association studies (MWAS) aimed at interrogating all methylation sites in the human genome. When using blood as biomaterial for a MWAS the DNA is typically extracted directly from fresh or frozen whole blood that was collected via venous puncture. However, DNA extracted from dry blood spots may also be an alternative starting material. In the present study, we apply a methyl-CpG binding domain (MBD) protein enrichment-based technique in combination with next generation sequencing (MBD-seq) to assess the methylation status of the similar to 27 million CpGs in the human autosomal reference genome. We investigate eight methylomes using DNA from blood spots. This data are compared with 1,500 methylomes previously assayed with the same MBD-seq approach using DNA from whole blood. When investigating the sequence quality and the enrichment profile across biological features, we find that DNA extracted from blood spots gives comparable results with DNA extracted from whole blood. Only if the amount of starting material is