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Repeat expansion and methylation state analysis with nanopore sequencing
Pay Gießelmann, Björn Brändl, Etienne Raimondeau, Rebecca Bowen, Christian Rohrandt, Rashmi Tandon, Helene Kretzmer, Günter Assum, Christina Galonska, Reiner Siebert, Ole Ammerpohl, Andrew Heron, Susanne A. Schneider, Julia Ladewig, Philipp Koch, Bernhard M. Schuldt, James E. Graham, Alexander Meissner, Franz-Josef Müller
doi: https://doi.org/10.1101/480285
Pay Gießelmann
1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, (Berlin, Germany)
Björn Brändl
1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, (Berlin, Germany)
2Universitätsklinikum Schleswig-Holstein Campus Kiel, Zentrum für Integrative Psychiatrie gGmbH (Kiel, Germany)
Etienne Raimondeau
3Oxford Nanopore Technologies (Oxford, UK)
Rebecca Bowen
3Oxford Nanopore Technologies (Oxford, UK)
Christian Rohrandt
4Kiel University of Applied Sciences, Institute for Communications Technology and Microelectronics (Kiel, Germany)
Rashmi Tandon
2Universitätsklinikum Schleswig-Holstein Campus Kiel, Zentrum für Integrative Psychiatrie gGmbH (Kiel, Germany)
Helene Kretzmer
1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, (Berlin, Germany)
Günter Assum
5Institute for Human Genetics, Ulm University and Ulm University Medical Center (Ulm, Germany)
Christina Galonska
1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, (Berlin, Germany)
Reiner Siebert
5Institute for Human Genetics, Ulm University and Ulm University Medical Center (Ulm, Germany)
Ole Ammerpohl
5Institute for Human Genetics, Ulm University and Ulm University Medical Center (Ulm, Germany)
Andrew Heron
3Oxford Nanopore Technologies (Oxford, UK)
Susanne A. Schneider
6Department of Neurology, Ludwig-Maximilians- Universität (München, Germany)
Julia Ladewig
7Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University (Mannheim, Germany)
8HITBR Hector Institute for Translational Brain Research gGmbH (Heidelberg, Germany)
9German Cancer Research Center (DKFZ) (Heidelberg, Germany)
10Institute of Reconstructive Neurobiology, University of Bonn Medical Center (Bonn, Germany)
Philipp Koch
7Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University (Mannheim, Germany)
8HITBR Hector Institute for Translational Brain Research gGmbH (Heidelberg, Germany)
9German Cancer Research Center (DKFZ) (Heidelberg, Germany)
Bernhard M. Schuldt
2Universitätsklinikum Schleswig-Holstein Campus Kiel, Zentrum für Integrative Psychiatrie gGmbH (Kiel, Germany)
James E. Graham
3Oxford Nanopore Technologies (Oxford, UK)
Alexander Meissner
1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, (Berlin, Germany)
11Department of Stem Cell and Regenerative Biology, Harvard University (Cambridge, USA)
Franz-Josef Müller
1Department of Genome Regulation, Max Planck Institute for Molecular Genetics, (Berlin, Germany)
2Universitätsklinikum Schleswig-Holstein Campus Kiel, Zentrum für Integrative Psychiatrie gGmbH (Kiel, Germany)
Abstract
Expansions of short tandem repeats are genetic variants that have been implicated in neuropsychiatric and other disorders but their assessment remains challenging with current molecular methods. Here, we developed a Cas12a-based enrichment strategy for nanopore sequencing that, combined with a new algorithm for raw signal analysis, enables us to efficiently target, sequence and precisely quantify repeat numbers as well as their DNA methylation status. Taking advantage of these single molecule nanopore signals provides therefore unprecedented opportunities to study pathological repeat expansions.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted November 28, 2018.
Repeat expansion and methylation state analysis with nanopore sequencing
Pay Gießelmann, Björn Brändl, Etienne Raimondeau, Rebecca Bowen, Christian Rohrandt, Rashmi Tandon, Helene Kretzmer, Günter Assum, Christina Galonska, Reiner Siebert, Ole Ammerpohl, Andrew Heron, Susanne A. Schneider, Julia Ladewig, Philipp Koch, Bernhard M. Schuldt, James E. Graham, Alexander Meissner, Franz-Josef Müller
bioRxiv 480285; doi: https://doi.org/10.1101/480285
Repeat expansion and methylation state analysis with nanopore sequencing
Pay Gießelmann, Björn Brändl, Etienne Raimondeau, Rebecca Bowen, Christian Rohrandt, Rashmi Tandon, Helene Kretzmer, Günter Assum, Christina Galonska, Reiner Siebert, Ole Ammerpohl, Andrew Heron, Susanne A. Schneider, Julia Ladewig, Philipp Koch, Bernhard M. Schuldt, James E. Graham, Alexander Meissner, Franz-Josef Müller
bioRxiv 480285; doi: https://doi.org/10.1101/480285
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