Title

Free energy of DNA duplex formation on short oligonucleotide microarrays

Authors

Authors

L. Zhang; C. L. Wu; R. Carta;H. T. Zhao

Comments

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Abbreviated Journal Title

Nucleic Acids Res.

Keywords

GENE-EXPRESSION; ARRAYS; HYBRIDIZATION; GENOMICS; Biochemistry & Molecular Biology

Abstract

DNA/DNA duplex formation is the basic mechanism that is used in genome tiling arrays and SNP arrays manufactured by Affymetrix. However, detailed knowledge of the physical process is still lacking. In this study, we show a free energy analysis of DNA/DNA duplex formation these arrays based on the positional-dependent nearest-neighbor (PDNN) model, which was developed previously for describing DNA/RNA duplex formation on expression microarrays. Our results showed that the two ends of a probe contribute less to the stability of the duplexes and that there is a microarray surface effect on binding affinities. We also showed that free energy cost of a single mismatch depends on the bases adjacent to the mismatch site and obtained a comprehensive table of the cost of a single mismatch under all possible combination of adjacent bases. The mismatch costs were found to be correlated with those determined in aqueous solution. We further demonstrate that the DNA copy number estimated from the SNP array correlates negatively with the target length; this is presumably caused by inefficient PCR amplification for long fragments. These results provide important insights into the molecular mechanisms of microarray technology and have implications for microarray design and the interpretation of observed data.

Journal Title

Nucleic Acids Research

Volume

35

Issue/Number

3

Publication Date

1-1-2007

Document Type

Article

Language

English

First Page

5

WOS Identifier

WOS:000244429800005

ISSN

0305-1048

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