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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384221/
https://www.ncbi.nlm.nih.gov/pubmed/28382928
http://dx.doi.org/10.1038/ncomms14738
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author 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
author_facet 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
author_sort Zhang, Honglu
collection PubMed
description 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.
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spelling pubmed-53842212017-04-23 DNA origami-based shape IDs for single-molecule nanomechanical genotyping 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 Nat Commun Article 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. Nature Publishing Group 2017-04-06 /pmc/articles/PMC5384221/ /pubmed/28382928 http://dx.doi.org/10.1038/ncomms14738 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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
DNA origami-based shape IDs for single-molecule nanomechanical genotyping
title DNA origami-based shape IDs for single-molecule nanomechanical genotyping
title_full DNA origami-based shape IDs for single-molecule nanomechanical genotyping
title_fullStr DNA origami-based shape IDs for single-molecule nanomechanical genotyping
title_full_unstemmed DNA origami-based shape IDs for single-molecule nanomechanical genotyping
title_short DNA origami-based shape IDs for single-molecule nanomechanical genotyping
title_sort dna origami-based shape ids for single-molecule nanomechanical genotyping
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384221/
https://www.ncbi.nlm.nih.gov/pubmed/28382928
http://dx.doi.org/10.1038/ncomms14738
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