Genome-wide analysis of DNA methylation profiles in a senescence-accelerated mouse prone 8 brain using whole-genome bisulfite sequencing

Abstract

Motivation: 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. Results: 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.