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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 and Juan M. Vaquerizas ()
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Noelia Díaz: Max Planck Institute for Molecular Biomedicine
Kai Kruse: Max Planck Institute for Molecular Biomedicine
Tabea Erdmann: University Hospital Muenster
Annette M. Staiger: Robert-Bosch-Hospital
German Ott: Robert-Bosch-Hospital
Georg Lenz: University Hospital Muenster
Juan M. Vaquerizas: Max Planck Institute for Molecular Biomedicine

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06961-0

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