Abstract
Although approximately 1 in 500 individuals carries a reciprocal translocation, little is known about the mechanisms that result in their formation. We analyzed the sequences surrounding the breakpoints in three unbalanced translocations of 1p and 9q, all of which were designated t(1;9)(p36.3;q34), to investigate the presence of sequence motifs that might mediate nonhomologous end joining (NHEJ). The breakpoint regions were unique in all individuals. Two of three translocations demonstrated insertions and duplications at the junctions, suggesting NHEJ in the formation of the rearrangements. No homology was identified in the breakpoint regions, further supporting NHEJ. We found translin motifs at the breakpoint junctions, suggesting the involvement of translin in the joining of the broken chromosome ends. We propose a model for balanced translocation formation in humans similar to transposition in bacteria, in which staggered nicks are repaired resulting in duplications and insertions at the translocation breakpoints.
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Acknowledgments
We thank A. Theisen (Washington State University, Spokane, WA, USA) for his critical editing of the manuscript, Dr. P. Shing Ho (Oregon State University, Corvallis, OR, USA) for his help with the ZHUNT program and Z-DNA prediction, and Drs. J. Lupski (Baylor College of Medicine, Houston, TX, USA) and B. Morrow (Albert Einstein College of Medicine, Bronx, NY) for helpful discussions. This work was supported in part from a National Institutes of Health PO1 (HD39420).
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Gajecka, M., Pavlicek, A., Glotzbach, C.D. et al. Identification of sequence motifs at the breakpoint junctions in three t(1;9)(p36.3;q34) and delineation of mechanisms involved in generating balanced translocations. Hum Genet 120, 519–526 (2006). https://doi.org/10.1007/s00439-006-0222-1
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DOI: https://doi.org/10.1007/s00439-006-0222-1