Abstract
Structural variations (SVs), including translocations, inversions, deletions and duplications, are potentially associated with Mendelian diseases and contiguous gene syndromes. Determination of SV-related breakpoints at the nucleotide level is important to reveal the genetic causes for diseases. Whole-genome sequencing (WGS) by next-generation sequencers is expected to determine structural abnormalities more directly and efficiently than conventional methods. In this study, 14 SVs (9 balanced translocations, 1 inversion and 4 microdeletions) in 9 patients were analyzed by WGS with a shallow (5 × ) to moderate read coverage (20 × ). Among 28 breakpoints (as each SV has two breakpoints), 19 SV breakpoints had been determined previously at the nucleotide level by any other methods and 9 were uncharacterized. BreakDancer and Integrative Genomics Viewer determined 20 breakpoints (16 translocation, 2 inversion and 2 deletion breakpoints), but did not detect 8 breakpoints (2 translocation and 6 deletion breakpoints). These data indicate the efficacy of WGS for the precise determination of translocation and inversion breakpoints.
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Acknowledgements
We thank all the patients and their families for their participation in this study. We also thank Nobuko Watanabe for her technical assistance. This work was supported by the Ministry of Health, Labour and Welfare of Japan; the Japan Society for the Promotion of Science (a Grant-in-Aid for Scientific Research (B), and a Grant-in-Aid for Scientific Research (A)); the Takeda Science Foundation; the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems; the Strategic Research Program for Brain Sciences; and a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Suzuki, T., Tsurusaki, Y., Nakashima, M. et al. Precise detection of chromosomal translocation or inversion breakpoints by whole-genome sequencing. J Hum Genet 59, 649–654 (2014). https://doi.org/10.1038/jhg.2014.88
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DOI: https://doi.org/10.1038/jhg.2014.88
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