March 08, 2018
Sponsored by
Swift Biosciences

Optimized Next Generation Sequencing Protocol for Comprehensive and Cost-Effective Methylome-Wide Association Studies


Assistant Professor, Center for Biomarker Research and Precision Medicine, School of Pharmacy, Virginia Commonwealth University

This webinar discusses an optimized protocol for methyl-CpG binding domain sequencing (MBD-seq), which enables comprehensive, adequately powered, and cost-effective large-scale methylome-wide association studies (MWAS) of almost all 28 million CpG sites in the genome.

Studies of DNA methylation provide a promising route to gain further insight into many complex phenotypes, but detailed biological knowledge linking specific methylation sites to phenotypes is lacking, making MWAS critical. Whole genome bisulfite sequencing (WGB-seq) provides comprehensive coverage of the methylome, but is not yet practically feasible with the sample sizes required for MWAS. This limitation may explain why MWAS is commonly performed using microarray-based technologies, which assay only a very small fraction of the methylome.

Comparisons show that optimized MBD-seq approximates the coverage obtained with WGB-seq, but this performance is achieved at a fraction (~5%) of the reagent costs for WGB-seq, bringing it within the approximate price point of array-based methods. The MBD-seq protocol also allows for as little as 5-50 ng of high-quality genomic DNA as input, which allows for many sample types of limited availability to be assayed.

In this webinar, Karolina Åberg of Virginia Commonwealth University presents findings from MWASs of major depressive disorder and childhood trauma using DNA from brain, whole blood, and blood spots to provide a proof of concept that MBD-seq based MWAS can shed light on disease etiology and identify potential clinical biomarkers.

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