DNA origami-based shape IDs for single-molecule nanomechanical genotyping

Variations on DNA sequences profoundly affect how we develop diseases and respond to pathogens and drugs. Atomic force microscopy (AFM) provides a nanomechanical imaging approach for genetic analysis with nanometre resolution. However, unlike fluorescence imaging that has wavelength-specific fluorop...

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Vydáno v:Nature communications Ročník 8; číslo 1; s. 14738 - 7
Hlavní autoři: Zhang, Honglu, Chao, Jie, Pan, Dun, Liu, Huajie, Qiang, Yu, Liu, Ke, Cui, Chengjun, Chen, Jianhua, Huang, Qing, Hu, Jun, Wang, Lianhui, Huang, Wei, Shi, Yongyong, Fan, Chunhai
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 06.04.2017
Nature Publishing Group
Nature Portfolio
Témata:
639/638/45/56
639/925/926
Asian People - genetics
China
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - genetics
Genetic Predisposition to Disease
Genomes
Haplotypes
Humanities and Social Sciences
Humans
Hybridization
Labeling
Microscopy
Microscopy, Atomic Force
multidisciplinary
Nanotechnology
Nucleic Acid Conformation
Polymorphism, Single Nucleotide
Science
Science (multidisciplinary)
China
ISSN:2041-1723, 2041-1723
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Shrnutí:Variations on DNA sequences profoundly affect how we develop diseases and respond to pathogens and drugs. Atomic force microscopy (AFM) provides a nanomechanical imaging approach for genetic analysis with nanometre resolution. However, unlike fluorescence imaging that has wavelength-specific fluorophores, the lack of shape-specific labels largely hampers widespread applications of AFM imaging. Here we report the development of a set of differentially shaped, highly hybridizable self-assembled DNA origami nanostructures serving as shape IDs for magnified nanomechanical imaging of single-nucleotide polymorphisms. Using these origami shape IDs, we directly genotype single molecules of human genomic DNA with an ultrahigh resolution of ∼10 nm and the multiplexing ability. Further, we determine three types of disease-associated, long-range haplotypes in samples from the Han Chinese population. Single-molecule analysis allows robust haplotyping even for samples with low labelling efficiency. We expect this generic shape ID-based nanomechanical approach to hold great potential in genetic analysis at the single-molecule level. Atomic force microscopy allows for the imaging of molecules at a nanometre resolution. Here the authors combine AFM with self-assembling DNA origami structures to detect single-nucleotide polymorphisms and determine haplotypes.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms14738