Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.
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.
Cardiovascular Research Institute, University of California, San Francisco.
Angel C Y
http://orcid.org/0000-0002-5372-4198
AC
Mak
Cardiovascular Research Institute, University of California, San Francisco.
Yvonne Y Y
YY
Lai
BioNano Genomics.
Ernest T
ET
Lam
Department of Computer Science and Engineering, The Chinese University of Hong Kong.
Tsz-Piu
TP
Kwok
School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong.
Alden K Y
AK
Leung
Cardiovascular Research Institute, University of California, San Francisco.
Annie
A
Poon
Cardiovascular Research Institute, University of California, San Francisco.
Yulia
Y
Mostovoy
BioNano Genomics.
Alex R
AR
Hastie
BioNano Genomics.
William
W
Stedman
BioNano Genomics.
Thomas
T
Anantharaman
BioNano Genomics.
Warren
W
Andrews
BioNano Genomics.
Xiang
X
Zhou
BioNano Genomics.
Andy W C
AW
Pang
BioNano Genomics.
Heng
H
Dai
Cardiovascular Research Institute, University of California, San Francisco.
Catherine
C
Chu
Cardiovascular Research Institute, University of California, San Francisco.
Chin
C
Lin
Department of Computer Science, The University of Hong Kong.
Jacob J K
JJ
Wu
Department of Computer Science, The University of Hong Kong.
Catherine M L
CM
Li
School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong.
Jing-Woei
JW
Li
School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong.
Aldrin K Y
AK
Yim
BioNano Genomics.
Saki
S
Chan
School of Biomedical Engineering, Science and Health Systems, Drexel University.
Justin
J
Sibert
BioNano Genomics.
Željko
Ž
Džakula
BioNano Genomics.
Han
H
Cao
Department of Computer Science, The University of Hong Kong.
Siu-Ming
SM
Yiu
School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong.
Ting-Fung
TF
Chan
Department of Computer Science and Engineering, The Chinese University of Hong Kong Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong.
Kevin Y
KY
Yip
School of Biomedical Engineering, Science and Health Systems, Drexel University.
Ming
M
Xiao
Cardiovascular Research Institute, University of California, San Francisco Institute for Human Genetics, University of California, San Francisco pui.kwok@ucsf.edu.
Pui-Yan
PY
Kwok
D002460:Cell Line; D002874:Chromosome Mapping; D015894:Genome, Human; D056914:Genomic Structural Variation; D006801:Humans; D046228:Microarray Analysis / Q000379:methods*
biotechnology; genome mapping; structural variation detection