Genome-Wide Detection of Polymorphisms at Nucleotide Resolution with a Single DNA Microarray

Abstract

A central challenge of genomics is to detect, simply and inexpensively, all differences in sequence among the genomes of individual members of a species. We devised a system to detect all single-nucleotide differences between genomes with the use of data from a single hybridization to a whole-genome DNA microarray. This allowed us to detect a variety of spontaneous single–base pair substitutions, insertions, and deletions, and most (>90%) of the ∼30,000 known single-nucleotide polymorphisms between two Saccharomyces cerevisiae strains. We applied this approach to elucidate the genetic basis of phenotypic variants and to identify the small number of single–base pair changes accumulated during experimental evolution of yeast.