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Detecting SNPs using a synthetic nanopore

Q Zhao, G Sigalov, Valentin Dimitrov, B Dorvel, U Mirsaidov, S Sligar, Aleksei Aksimentiev, and Gregory Timp
Nano Lett 7(6) 1680-5 (2007)
DOI:10.1021/nl070668c  PMID:17500578  BibTex

We have discovered a voltage threshold for permeation through a synthetic nanopore of dsDNA bound to a restriction enzyme that depends on the sequence. Molecular dynamic simulations reveal that the threshold is associated with a nanonewton force required to rupture the DNA-protein complex. A single mutation in the recognition site for the restriction enzyme, i.e., a single nucleotide polymorphism (SNP), can easily be detected as a change in the threshold voltage. Consequently, by measuring the threshold voltage in a synthetic nanopore, it may be possible to discriminate between two variants of the same gene (alleles) that differ in one base.