Identification of Balanced Chromosomal Rearrangements Previously Unknown Among Participants in the 1000 Genomes Project: Implications for Interpretation of Structural Variation in Genomes and the Future of Clinical Cytogenetics
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Author
Dong, Zirui
Wang, Huilin
Chen, Haixiao
Jiang, Hui
Yuan, Jianying
Yang, Zhenjun
Wang, Wen-Jing
Xu, Fengping
Guo, Xiaosen
Cao, Ye
Zhu, Zhenzhen
Geng, Chunyu
Cheung, Wan Chee
Kwok, Yvonne K
Yang, Huangming
Leung, Tak Yeung
Cheung, Sau Wai
Choy, Kwong Wai
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https://doi.org/10.1038/gim.2017.170Metadata
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Dong, Z., H. Wang, H. Chen, H. Jiang, J. Yuan, Z. Yang, W. Wang, et al. 2017. “Identification of Balanced Chromosomal Rearrangements Previously Unknown Among Participants in the 1000 Genomes Project: Implications for Interpretation of Structural Variation in Genomes and the Future of Clinical Cytogenetics.” Genetics in medicine : official journal of the American College of Medical Genetics :10.1038/gim.2017.170. doi:10.1038/gim.2017.170. http://dx.doi.org/10.1038/gim.2017.170.Abstract
Purpose Recent studies demonstrate that whole-genome sequencing (WGS) enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in The 1000 Genomes Project without knowing affected bands. Methods: The 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparently BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold). Results: Our approach detected four reciprocal balanced translocations and four inversions ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and PCR studies. One of DNAs has a subtle translocation that is not readily identified by chromosome analysis due to similar banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene. Conclusions: Our study demonstrates the extension of utilizing low-coverage WGS for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932280/pdf/Terms of Use
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