Genome-wide detection of polymorphisms at nucleotide resolution with a single DNA microarray.
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.
Gresham
David
D
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. dgresham@genomics.princeton.edu
Ruderfer
Douglas M
DM
Pratt
Stephen C
SC
Schacherer
Joseph
J
Dunham
Maitreya J
MJ
Botstein
David
D
Kruglyak
Leonid
L
D019020:Directed Molecular Evolution; D005800:Genes, Fungal; D016681:Genome, Fungal; D023281:Genomics; D009154:Mutation; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D013489:Suppression, Genetic