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Chromatin conformation analysis of primary patient tissue using a low input Hi-C method

View ORCID ProfileNoelia Díaz, View ORCID ProfileKai Kruse, Tabea Erdmann, Annette M. Staiger, German Ott, Georg Lenz, View ORCID ProfileJuan M. Vaquerizas
doi: https://doi.org/10.1101/372789
Noelia Díaz
1Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, 48149 Muenster, Germany
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Kai Kruse
1Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, 48149 Muenster, Germany
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Tabea Erdmann
2Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany
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Annette M. Staiger
3Department of Clinical Pathology, Robert-Bosch-Hospital, Auerbachstrasse 110, 70376 Stuttgart, Germany
4Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 Stuttgart, Germany
5Eberhard Karls Universität Tübingen, Geschwister-Scholl-Platz, 72074 Tübingen, Germany
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German Ott
3Department of Clinical Pathology, Robert-Bosch-Hospital, Auerbachstrasse 110, 70376 Stuttgart, Germany
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Georg Lenz
2Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany
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Juan M. Vaquerizas
1Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, 48149 Muenster, Germany
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  • For correspondence: jmv@mpi-muenster.mpg.de
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Abstract

Chromatin conformation constitutes a fundamental level of eukaryotic genome regulation. However, our ability to examine its biological function and role in disease is limited by the large amounts of starting material required to perform current experimental approaches. Here, we present Low-C, a Hi-C method for low amounts of input material. By systematically comparing Hi-C libraries made with decreasing amounts of starting material we show that Low-C is highly reproducible and robust to experimental noise. To demonstrate the suitability of Low-C to analyse rare cell populations, we produce Low-C maps from primary B-cells of a diffuse large B-cell lymphoma patient. We detect a common reciprocal translocation t (3;14) (q27;q32) affecting the BCL6 and IGH loci and abundant local structural variation between the patient and healthy B-cells. The ability to study chromatin conformation in primary tissue will be fundamental to fully understand the molecular pathogenesis of diseases and to eventually guide personalised therapeutic strategies.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 19, 2018.
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Chromatin conformation analysis of primary patient tissue using a low input Hi-C method
Noelia Díaz, Kai Kruse, Tabea Erdmann, Annette M. Staiger, German Ott, Georg Lenz, Juan M. Vaquerizas
bioRxiv 372789; doi: https://doi.org/10.1101/372789
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Chromatin conformation analysis of primary patient tissue using a low input Hi-C method
Noelia Díaz, Kai Kruse, Tabea Erdmann, Annette M. Staiger, German Ott, Georg Lenz, Juan M. Vaquerizas
bioRxiv 372789; doi: https://doi.org/10.1101/372789

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