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Genome Res. 2019 Apr;29(4):646-656. doi: 10.1101/gr.240739.118. Epub 2019 Mar 7.

Long-read single-molecule maps of the functional methylome.

Author information

1
School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv 6997801, Israel.
2
Institute of Organic Chemistry RWTH Aachen University, D-52056 Aachen, Germany.
3
Center for Genetic Medicine Research, Children's National Health System, Children's Research Institute, Washington, DC 20010, USA.
4
Kennedy Krieger Institute and Departments of Neurology and Neuroscience, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
5
Bionano Genomics, Incorporated, San Diego, California 92121, USA.
#
Contributed equally

Abstract

We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spanning hundreds of kilobase pairs. The method provides kilobase pair-scale genomic methylation patterns comparable to whole-genome bisulfite sequencing (WGBS) along genes and regulatory elements. These long single-molecule reads allow for methylation variation calling and analysis of large structural aberrations such as pathogenic macrosatellite arrays not accessible to single-cell second-generation sequencing. The method is applied here to study facioscapulohumeral muscular dystrophy (FSHD), simultaneously recording the haplotype, copy number, and methylation status of the disease-associated, highly repetitive locus on Chromosome 4q.

Comment in

PMID:
30846530
PMCID:
PMC6442387
DOI:
10.1101/gr.240739.118
[Indexed for MEDLINE]
Free PMC Article

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