title: Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology.
abstract: BACKGROUND
  Structural variants (SVs) are less common than single nucleotide polymorphisms and indels in the population, but collectively account for a significant fraction of genetic polymorphism and diseases. Base pair differences arising from SVs are on a much higher order (>100 fold) than point mutations; however, none of the current detection methods are comprehensive, and currently available methodologies are incapable of providing sufficient resolution and unambiguous information across complex regions in the human genome. To address these challenges, we applied a high-throughput, cost-effective genome mapping technology to comprehensively discover genome-wide SVs and characterize complex regions of the YH genome using long single molecules (>150 kb) in a global fashion.
  
  
  RESULTS
  Utilizing nanochannel-based genome mapping technology, we obtained 708 insertions/deletions and 17 inversions larger than 1 kb. Excluding the 59 SVs (54 insertions/deletions, 5 inversions) that overlap with N-base gaps in the reference assembly hg19, 666 non-gap SVs remained, and 396 of them (60%) were verified by paired-end data from whole-genome sequencing-based re-sequencing or de novo assembly sequence from fosmid data. Of the remaining 270 SVs, 260 are insertions and 213 overlap known SVs in the Database of Genomic Variants. Overall, 609 out of 666 (90%) variants were supported by experimental orthogonal methods or historical evidence in public databases. At the same time, genome mapping also provides valuable information for complex regions with haplotypes in a straightforward fashion. In addition, with long single-molecule labeling patterns, exogenous viral sequences were mapped on a whole-genome scale, and sample heterogeneity was analyzed at a new level.
  
  
  CONCLUSIONS
  Our study highlights genome mapping technology as a comprehensive and cost-effective method for detecting structural variation and studying complex regions in the human genome, as well as deciphering viral integration into the host genome.
authors: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Transomics Biotechnologies, Shenzhen, 518083 China ; Department of Biology, University of Copenhagen, Copenhagen, 2200 Denmark.
authors: Hongzhi
authors: H
authors: Cao
authors: BioNano Genomics, San Diego, California 92121 USA.
authors: Alex R
authors: AR
authors: Hastie
authors: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Transomics Biotechnologies, Shenzhen, 518083 China.
authors: Dandan
authors: D
authors: Cao
authors: BioNano Genomics, San Diego, California 92121 USA.
authors: Ernest T
authors: ET
authors: Lam
authors: BGI-Shenzhen, Shenzhen, 518083 China ; School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, 511400 China.
authors: Yuhui
authors: Y
authors: Sun
authors: BGI-Shenzhen, Shenzhen, 518083 China ; School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, 511400 China.
authors: Haodong
authors: H
authors: Huang
authors: BGI-Shenzhen, Shenzhen, 518083 China ; Department of Biology, University of Copenhagen, Copenhagen, 2200 Denmark.
authors: Xiao
authors: X
authors: Liu
authors: BGI-Shenzhen, Shenzhen, 518083 China ; School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, 511400 China.
authors: Liya
authors: L
authors: Lin
authors: BioNano Genomics, San Diego, California 92121 USA.
authors: Warren
authors: W
authors: Andrews
authors: BioNano Genomics, San Diego, California 92121 USA.
authors: Saki
authors: S
authors: Chan
authors: BGI-Shenzhen, Shenzhen, 518083 China ; School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, 511400 China.
authors: Shujia
authors: S
authors: Huang
authors: BGI-Shenzhen, Shenzhen, 518083 China.
authors: Xin
authors: X
authors: Tong
authors: BioNano Genomics, San Diego, California 92121 USA.
authors: Michael
authors: M
authors: Requa
authors: BioNano Genomics, San Diego, California 92121 USA.
authors: Thomas
authors: T
authors: Anantharaman
authors: Department of Biology, University of Copenhagen, Copenhagen, 2200 Denmark.
authors: Anders
authors: A
authors: Krogh
authors: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Transomics Biotechnologies, Shenzhen, 518083 China.
authors: Huanming
authors: H
authors: Yang
authors: BioNano Genomics, San Diego, California 92121 USA.
authors: Han
authors: H
authors: Cao
authors: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Transomics Biotechnologies, Shenzhen, 518083 China.
authors: Xun
authors: X
authors: Xu
keywords: Epstein-Barr virus (EBV) integration; Genome mapping; Repeat units; Structural variation