Dataset Information

Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.

ABSTRACT: Comprehensive whole-genome structural variation detection is challenging with current approaches. With diploid cells as DNA source and the presence of numerous repetitive elements, short-read DNA sequencing cannot be used to detect structural variation efficiently. In this report, we show that genome mapping with long, fluorescently labeled DNA molecules imaged on nanochannel arrays can be used for whole-genome structural variation detection without sequencing. While whole-genome haplotyping is not achieved, local phasing (across >150-kb regions) is routine, as molecules from the parental chromosomes are examined separately. In one experiment, we generated genome maps from a trio from the 1000 Genomes Project, compared the maps against that derived from the reference human genome, and identified structural variations that are >5 kb in size. We find that these individuals have many more structural variants than those published, including some with the potential of disrupting gene function or regulation.

SUBMITTER: Mak AC

PROVIDER: S-EPMC4701098 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.

Mak Angel C Y AC Lai Yvonne Y Y YY Lam Ernest T ET Kwok Tsz-Piu TP Leung Alden K Y AK Poon Annie A Mostovoy Yulia Y Hastie Alex R AR Stedman William W Anantharaman Thomas T Andrews Warren W Zhou Xiang X Pang Andy W C AW Dai Heng H Chu Catherine C Lin Chin C Wu Jacob J K JJ Li Catherine M L CM Li Jing-Woei JW Yim Aldrin K Y AK Chan Saki S Sibert Justin J Džakula Željko Ž Cao Han H Yiu Siu-Ming SM Chan Ting-Fung TF Yip Kevin Y KY Xiao Ming M Kwok Pui-Yan PY

Genetics 20151028 1

Comprehensive whole-genome structural variation detection is challenging with current approaches. With diploid cells as DNA source and the presence of numerous repetitive elements, short-read DNA sequencing cannot be used to detect structural variation efficiently. In this report, we show that genome mapping with long, fluorescently labeled DNA molecules imaged on nanochannel arrays can be used for whole-genome structural variation detection without sequencing. While whole-genome haplotyping is ...[more]

PMID: 26510793

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Project description: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.

Dataset Information

Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.

Publications

Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.

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