Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology
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Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology. / Cao, Hongzhi; Hastie, Alex R.; Cao, Dandan; Lam, Ernest T.; Sun, Yuhui; Huang, Haodong; Liu, Xiao; Lin, Liya; Andrews, Warren; Chan, Saki; Huang, Shujia; Tong, Xin; Requa, Michael; Anantharaman, Thomas; Krogh, Anders; Yang, Huanming; Cao, Han; Xu, Xun.
In: GigaScience, Vol. 3, 34, 2014.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology
AU - Cao, Hongzhi
AU - Hastie, Alex R.
AU - Cao, Dandan
AU - Lam, Ernest T.
AU - Sun, Yuhui
AU - Huang, Haodong
AU - Liu, Xiao
AU - Lin, Liya
AU - Andrews, Warren
AU - Chan, Saki
AU - Huang, Shujia
AU - Tong, Xin
AU - Requa, Michael
AU - Anantharaman, Thomas
AU - Krogh, Anders
AU - Yang, Huanming
AU - Cao, Han
AU - Xu, Xun
PY - 2014
Y1 - 2014
N2 - 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.CONCLUSION: 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.
AB - 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.CONCLUSION: 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.
U2 - 10.1186/2047-217X-3-34
DO - 10.1186/2047-217X-3-34
M3 - Journal article
C2 - 25671094
VL - 3
JO - GigaScience
JF - GigaScience
SN - 2047-217X
M1 - 34
ER -
ID: 136791524