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Published Online March 9, 2006
Science DOI: 10.1126/science.1123726

Reports

Submitted on December 12, 2005
Accepted on February 24, 2006

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

David Gresham 1*, Douglas M. Ruderfer 2, Stephen C. Pratt 2, Joseph Schacherer 2, Maitreya Dunham 3, David Botstein 1, Leonid Kruglyak 2*

1 Lewis-Sigler Institute for Integrative Genomics; Department of Molecular Biology
2 Lewis-Sigler Institute for Integrative Genomics; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.
3 Lewis-Sigler Institute for Integrative Genomics

* To whom correspondence should be addressed.
David Gresham , E-mail: dgresham{at}genomics.princeton.edu
Leonid Kruglyak , E-mail: leonid{at}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 using 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 identify the small number of single base-pair changes accumulated during experimental evolution of yeast.


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