Article abstract
Nature Methods 6, 837 - 842 (2009)
Published online: 11 October 2009 | doi:10.1038/nmeth.1391
High-resolution identification of balanced and complex chromosomal rearrangements by 4C technology
Marieke Simonis1,5, Petra Klous1,5, Irene Homminga2, Robert-Jan Galjaard3, Erik-Jan Rijkers4, Frank Grosveld5, Jules P P Meijerink2 & Wouter de Laat1,5
Abstract
Balanced chromosomal rearrangements can cause disease, but techniques for their rapid and accurate identification are missing. Here we demonstrate that chromatin conformation capture on chip (4C) technology can be used to screen large genomic regions for balanced and complex inversions and translocations at high resolution. The 4C technique can be used to detect breakpoints also in repetitive DNA sequences as it uniquely relies on capturing genomic fragments across the breakpoint. Using 4C, we uncovered LMO3 as a potentially leukemogenic translocation partner of TRB@. We developed multiplex 4C to simultaneously screen for translocation partners of multiple selected loci. We identified unsuspected translocations and complex rearrangements. Furthermore, using 4C we detected translocations even in small subpopulations of cells. This strategy opens avenues for the rapid fine-mapping of cytogenetically identified translocations and inversions, and the efficient screening for balanced rearrangements near candidate loci, even when rearrangements exist only in subpopulations of cells.
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, The Netherlands.
- Department of Pediatric Oncology, Erasmus Medical Center, Rotterdam, The Netherlands.
- Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
- Department of Biochemistry, Erasmus Medical Center, Rotterdam, The Netherlands.
- Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands.
Correspondence to: Wouter de Laat1,5 e-mail: w.delaat@hubrecht.eu
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