Open Access Highly Accessed Research article

Optical mapping discerns genome wide DNA methylation profiles

Gene E Ananiev1, Steve Goldstein1, Rod Runnheim1, Dan K Forrest1, Shiguo Zhou1, Konstantinos Potamousis1, Chris P Churas1, Veit Bergendahl2, James A Thomson2 and David C Schwartz1*

Author Affiliations

1 Department of Chemistry, Department of Genetics, Laboratory for Molecular and Computational Genomics, University of Wisconsin Biotechnology Center, University of Wisconsin-Madison, Madison WI 53706, USA

2 Department of Anatomy, the Primate Center, University of Wisconsin Biotechnology Center, University of Wisconsin-Madison, Madison WI 53706, USA

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BMC Molecular Biology 2008, 9:68  doi:10.1186/1471-2199-9-68

Published: 30 July 2008



Methylation of CpG dinucleotides is a fundamental mechanism of epigenetic regulation in eukaryotic genomes. Development of methods for rapid genome wide methylation profiling will greatly facilitate both hypothesis and discovery driven research in the field of epigenetics. In this regard, a single molecule approach to methylation profiling offers several unique advantages that include elimination of chemical DNA modification steps and PCR amplification.


A single molecule approach is presented for the discernment of methylation profiles, based on optical mapping. We report results from a series of pilot studies demonstrating the capabilities of optical mapping as a platform for methylation profiling of whole genomes. Optical mapping was used to discern the methylation profile from both an engineered and wild type Escherichia coli. Furthermore, the methylation status of selected loci within the genome of human embryonic stem cells was profiled using optical mapping.


The optical mapping platform effectively detects DNA methylation patterns. Due to single molecule detection, optical mapping offers significant advantages over other technologies. This advantage stems from obviation of DNA modification steps, such as bisulfite treatment, and the ability of the platform to assay repeat dense regions within mammalian genomes inaccessible to techniques using array-hybridization technologies.