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Journal Article

Position dependent mismatch discrimination on DNA microarrays - experiments and model

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Naiser, T., Kayser, J., Mai, T., Michel, W., & Ott, A. (2008). Position dependent mismatch discrimination on DNA microarrays - experiments and model. BMC BIOINFORMATICS, 9: 509. doi:10.1186/1471-2105-9-509.

Cite as: https://hdl.handle.net/21.11116/0000-000F-2E47-F
Background: The propensity of oligonucleotide strands to form stable
duplexes with complementary sequences is fundamental to a variety of
biological and biotechnological processes as various as microRNA
signalling, microarray hybridization and PCR. Yet our understanding of
oligonucleotide hybridization, in particular in presence of surfaces, is
rather limited. Here we use oligonucleotide microarrays made in-house by
optically controlled DNA synthesis to produce probe sets comprising all
possible single base mismatches and base bulges for each of 20 sequence
motifs under study.
Results: We observe that mismatch discrimination is mostly determined by
the defect position (relative to the duplex ends) as well as by the
sequence context. We investigate the thermodynamics of the
oligonucleotide duplexes on the basis of double-ended molecular zipper.
Theoretical predictions of defect positional influence as well as long
range sequence influence agree well with the experimental results.
Conclusion: Molecular zipping at thermodynamic equilibrium explains the
binding affinity of mismatched DNA duplexes on microarrays well. The
position dependent nearest neighbor model (PDNN) can be inferred from
it. Quantitative understanding of microarray experiments from first
principles is in reach.