Zhang Shuai, Qin Chunxia, Cao Guoqiong, Guo Limin, Feng Chengqiang, Zhang Wensheng
Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China.
Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.
Bioinformatics. 2017 Jun 1;33(11):1591-1595. doi: 10.1093/bioinformatics/btx040.
The pathogenesis of AD is complex and contributed by both genetic and environmental factors. Recent work revealed a potential link between DNA methylation and AD. However, a genome-wide study to identify potential DNA methylation sites involved in AD is still at an early stage. WGBS, an up-to-date technology, was used in this study. We investigated mouse brain genome-wide DNA methylation profiles between seven-month-old SAMP8 and SAMR1 models through deep WGBS.
According to the results, the global ML slightly decreased in the SAMP8 mice than in the SAMR1 mice (4.12% versus 4.19%). A total of 1 307 172 280 clean reads were obtained. Subsequently, we identified 63 DMRs from all cases in SAMP8 mice relative to SAMR1 mice. In addition, 26 DMR-related genes were detected. GO analyses revealed that these DMR-related genes were involved in regulating the development of AD from different aspects. Finally, three differentially expressed DMR-related genes ( Dlgap1 , TMEM51 and Eif2ak2 ) that were most likely involved in AD were summarized and listed in detail. Our study provided a systematic exploration of DNA methylation profiles in SAMP8 mouse brain for the first time. These novel methylation sites may be considered strong future candidates to combat this life-threatening disease.
The WGBS sequencing clean data and RNA-seq clean data have been deposited in the NCBI Sequence Read Archive (SRA).The accession number of WGBS is SRP097054. The accession number of RNA-seq is SRP096779.
Supplementary data are available at Bioinformatics online.
阿尔茨海默病（AD）的发病机制复杂，由遗传和环境因素共同导致。近期研究揭示了DNA甲基化与AD之间的潜在联系。然而，一项全基因组研究以确定参与AD的潜在DNA甲基化位点仍处于早期阶段。本研究采用了最新技术全基因组亚硫酸氢盐测序（WGBS）。我们通过深度WGBS研究了7月龄快速老化模型小鼠8（SAMP8）和抗快速老化模型小鼠1（SAMR1）之间的全基因组DNA甲基化谱。
结果显示，SAMP8小鼠的整体甲基化水平略低于SAMR1小鼠（4.12%对4.19%）。共获得1307172280条清洁 reads。随后，我们在SAMP8小鼠相对于SAMR1小鼠的所有样本中鉴定出63个差异甲基化区域（DMR）。此外，检测到26个与DMR相关的基因。基因本体（GO）分析表明，这些与DMR相关的基因从不同方面参与AD的发展调控。最后，总结并详细列出了最有可能参与AD的三个差异表达的与DMR相关的基因（Dlgap1、TMEM51和Eif2ak2）。我们的研究首次对SAMP8小鼠大脑中的DNA甲基化谱进行了系统探索。这些新的甲基化位点可能被视为未来对抗这种危及生命疾病的有力候选靶点。
WGBS测序的清洁数据和RNA测序的清洁数据已存入NCBI序列读取存档（SRA）。WGBS的登录号为SRP097054。RNA测序的登录号为SRP096779。
补充数据可在《生物信息学》在线获取。
