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Updated: Oct 11, 2026

Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
Protocol for genome-wide differential methylation using long-read DNA sequencing in the cortex of a mouse model of
Ümran Yaman1, Emil Gustavsson2, Jasmaine Lee3
1UK Dementia Research Institute at UCL, Gower Street, London WC1E 6BT, UK; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; Department of Cognitive Neuroscience, Institute of Neurological Sciences, İstanbul-Cerrahpaşa University, İstanbul 34098, Türkiye; Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Abstract:
Third-generation sequencing enables direct detection of genome-wide 5-methylcytosine without bisulfite conversion. Here, we present a protocol for generating long-read DNA sequencing from mouse cortex and performing genome-wide differential methylation analysis. We describe steps for high-molecular-weight DNA extraction, data generation, and downstream analysis. We demonstrate the workflow in the AppNL-G-F mouse model of amyloid pathology and provide a reproducible pipeline that links modified-base BAM (modBAM) files to annotated differentially methylated regions and functional enrichment results.

