title: A robust approach for blind detection of balanced chromosomal rearrangements with whole-genome low-coverage sequencing.
abstract: Balanced chromosomal rearrangement (or balanced chromosome abnormality, BCA) is a common chromosomal structural variation. Next-generation sequencing has been reported to detect BCA-associated breakpoints with the aid of karyotyping. However, the complications associated with this approach and the requirement for cytogenetics information has limited its application. Here, we provide a whole-genome low-coverage sequencing approach to detect BCA events independent of knowing the affected regions and with low false positives. First, six samples containing BCAs were used to establish a detection protocol and assess the efficacy of different library construction approaches. By clustering anomalous read pairs and filtering out the false-positive results with a control cohort and the concomitant mapping information, we could directly detect BCA events for each sample. Through optimizing the read depth, BCAs in all samples could be blindly detected with only 120 million read pairs per sample for data from a small-insert library and 30 million per sample for data from nonsize-selected mate-pair library. This approach was further validated using another 13 samples that contained BCAs. Our approach advances the application of high-throughput whole-genome low-coverage analysis for robust BCA detection-especially for clinical samples-without the need for karyotyping.
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Zirui
authors.initials: Z
authors.lastname: Dong
authors.forename: Lupin
authors.initials: L
authors.lastname: Jiang
authors.forename: Chuanchun
authors.initials: C
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Hu
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Wang
authors.forename: Haixiao
authors.initials: H
authors.lastname: Chen
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: Huamei
authors.initials: H
authors.lastname: Hu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Dong
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Juchun
authors.initials: J
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Long
authors.forename: Sujie
authors.initials: S
authors.lastname: Cao
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Fengping
authors.initials: F
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liang
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics; D002874:Chromosome Mapping; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D014178:Translocation, Genetic
keywords: balanced chromosomal rearrangement; blind detection; next-generation sequencing; whole-genome low coverage