Theoretical Aspects of Genomic Variation Screening Using DNA Microarrays

Arnold Vainrub, Bernard Pettitt

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We present a theoretical model for typical microarray-based single nucleotide polymorphism (SNP) assay of small genomic DNA amount. We derived the adsorption isotherm expressing the on-array hybridization efficiency in terms of genomic target sequence and concentration, oligonucleotide probe sequence and surface density, hybridization buffer, and temperature. This isotherm correctly describes the surface probe density effects, the sensitivity peak, and the melting temperature depression, and is in accord with published experiments. We discuss optimization of parallel SNP genotyping. Our estimates show that SNP detection at a single temperature in aqueous hybridization buffer is restricted by DNA regions that differ by less than 20% in GC content. We predict that the variety of genotyped SNPs could be substantially extended using an assay design with high probe density and a large fraction of probes hybridized.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalBiopolymers
Volume73
Issue number5
DOIs
StatePublished - Apr 5 2004
Externally publishedYes

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Keywords

  • Hybridization
  • Isotherm
  • Microarray
  • SNPs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

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