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Open Access Research article

Position dependent mismatch discrimination on DNA microarrays – experiments and model

Thomas Naiser1*, Jona Kayser1, Timo Mai1, Wolfgang Michel1 and Albrecht Ott12

Author Affiliations

1 Experimentalphysik I, Universität Bayreuth, D-95440 Bayreuth, Germany

2 Experimentalphysik, Universität des Saarlandes, D-66041 Saarbrücken, Germany

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BMC Bioinformatics 2008, 9:509  doi:10.1186/1471-2105-9-509

Published: 1 December 2008

Abstract

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.