Detecting SNPs using a synthetic nanopore.
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.
Zhao
Q
Q
Beckman Institute, University of Illinois, Urbana, Illinois 61801, USA.
Sigalov
G
G
Dimitrov
V
V
Dorvel
B
B
Mirsaidov
U
U
Sligar
S
S
Aksimentiev
A
A
Timp
G
G
D004247:DNA / Q000737:chemistry* / Q000235:genetics* / Q000528:radiation effects; D004252:DNA Mutational Analysis / Q000379:methods*; D015246:Deoxyribonuclease EcoRI / Q000737:chemistry*; D004574:Electromagnetic Fields; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016062:Porosity; D017422:Sequence Analysis, DNA / Q000379:methods; D013499:Surface Properties
D046911:Macromolecular Substances; D004247:DNA; D015246:Deoxyribonuclease EcoRI