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Theoretical aspects of genomic variation screening using DNA microarrays
Author(s) -
Vainrub Arnold,
Pettitt B. Montgomery
Publication year - 2004
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20008
Subject(s) - genotyping , dna microarray , snp genotyping , single nucleotide polymorphism , chemistry , oligonucleotide , snp , hybridization probe , molecular inversion probe , genomic dna , dna , microbiology and biotechnology , chromatography , genotype , biology , gene , biochemistry , gene expression
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. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004