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

Bioinformatics. 2017 Jun 1;33(11):1591-1595. doi: 10.1093/bioinformatics/btx040.


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.

Availability and implementation: 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 information: Supplementary data are available at Bioinformatics online.

MeSH terms

  • Aging / genetics*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology
  • Animals
  • Brain / physiopathology*
  • DNA Methylation*
  • Disease Models, Animal
  • Male
  • Mice
  • Sequence Analysis, RNA
  • Whole Genome Sequencing