High-resolution identification of balanced and complex chromosomal rearrangements by 4C technology.

TY - JOUR

T1 - High-resolution identification of balanced and complex chromosomal rearrangements by 4C technology.

AU - Simonis, M.

AU - Klous, P.

AU - Homminga, I.

AU - Galjaard, R.J.

AU - Rijkers, E.J.

AU - Grosveld, F.

AU - Meijerink, J.P.

AU - de Laat, W.

N1 - Reporting year: 2009

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1038/NMETH.1391

DO - 10.1038/NMETH.1391

M3 - Article

SN - 1548-7091

VL - 6

SP - 837

EP - 842

JO - Nature Methods

JF - Nature Methods

IS - 11

ER -