DNA methylation analysis for screening and diagnostic testing in neurodevelopmental disorders

Area of Science:

• Genetics
• Epigenetics
• Neuroscience

Background:

• DNA methylation (mDNA) is implicated in neurodevelopmental disorders (NDDs).
• Current diagnostic methods are often locus-specific for monogenic syndromes.
• Genome-wide methylation analysis (GWMA) offers a broader approach for NDD diagnosis.

Purpose of the Study:

• To review current genome-wide methylation analysis (GWMA) for neurodevelopmental disorders (NDDs).
• To identify barriers and limitations of existing GWMA technologies.
• To discuss future directions for improved NDD diagnostics.

Main Methods:

• Review of recent studies on genome-wide methylation analysis (GWMA).
• Analysis of limitations including coverage, sensitivity, and technical bias.
• Exploration of emerging direct methylation analysis techniques.

Main Results:

• GWMA can detect methylation changes in NDD probands, including those negative by exome sequencing.
• Existing array-based GWMA methods face challenges with regulatory region coverage and sensitivity.
• Indirect methylation analysis introduces technical bias.

Conclusions:

• Direct analysis of DNA methylation (mDNA) using long-read technologies is a promising future direction.
• Biomarkers like 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) warrant further investigation for NDDs.
• Advancements in methylation analysis are needed for more accurate NDD diagnosis.