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

Honglu Zhang, Jie Chao (), Dun Pan, Huajie Liu, Yu Qiang, Ke Liu, Chengjun Cui, Jianhua Chen, Qing Huang, Jun Hu, Lianhui Wang, Wei Huang, Yongyong Shi () and Chunhai Fan ()
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Honglu Zhang: Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Jie Chao: Key Laboratory for Organic Electronics and Information Displays (KLOEID), Institute of Advanced Materials (IAM), School of Materials Science and Engineering, Nanjing University of Posts and Telecommunications
Dun Pan: Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Huajie Liu: Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Yu Qiang: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University
Ke Liu: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University
Chengjun Cui: Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Jianhua Chen: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University
Qing Huang: Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Jun Hu: Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences
Lianhui Wang: Key Laboratory for Organic Electronics and Information Displays (KLOEID), Institute of Advanced Materials (IAM), School of Materials Science and Engineering, Nanjing University of Posts and Telecommunications
Wei Huang: Key Laboratory for Organic Electronics and Information Displays (KLOEID), Institute of Advanced Materials (IAM), School of Materials Science and Engineering, Nanjing University of Posts and Telecommunications
Yongyong Shi: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University
Chunhai Fan: Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-7

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14738

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