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

Nat Commun. 2017 Apr 6:8:14738. doi: 10.1038/ncomms14738.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • China
  • DNA / chemistry*
  • DNA / genetics*
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Humans
  • Microscopy, Atomic Force
  • Nanotechnology*
  • Nucleic Acid Conformation*
  • Polymorphism, Single Nucleotide

Substances

  • DNA