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Science. 2006 Mar 31;311(5769):1932-6. Epub 2006 Mar 9.

Genome-wide detection of polymorphisms at nucleotide resolution with a single DNA microarray.

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  • 1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. dgresham@genomics.princeton.edu


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 approximately 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.

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