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Genome-Wide mapping of Polymorphisms at Nucleotide Resolution with a Single DNA Array

Princeton Invention # 06-2269

A central challenge of genomics is to detect, simply and inexpensively, any and all differences in sequence among the genomes of individual members of a species. Researchers at the Lewis-Sigler Institute for Integrative Genomics, Princeton University , have devised a system using high-density Affymetrix yeast tiling  microarrays that detects single-nucleotide differences between yeast genomes and maps them to within a few nucleotides on a reference sequence, without any prior knowledge of their location. They have developed an analysis algorithm, SNPscanner©, which uses data from a single hybridization to a 5-fold redundant tiling DNA microarray of the entire reference genome sequence for Saccharomyces cerevisiae. This system has made it possible to find, in the yeast genome, a variety of single spontaneous base-pair mutations in different genes, single base-pair and gene-size insertions and deletions (indels), and to find most (90%) of the ~30,000 known single-nucleotide polymorphisms between two Saccharomyces cerevisiae yeast strains.  This genomic approach was used by the Princeton researchers to elucidate the genetic basis of additional spontaneous variants: mutations in AEP3 with opposite growth effects on non-fermentable carbon sources and an unexpected deletion of ACE2 responsible for suppression of the amn1 null phenotype.  Additionally they were able to document and place a small upper limit on the number of single base-pair changes accumulated during adaptive evolution over about 100 generations of continuous culture. 

Currently, DNA microarrays are used for studying the expression of genes and the determination of gene copy number changes of large segments of DNA. Developing methods to sequence whole genomes is an active area of development in corporate and academic settings.

This invention extends the use of DNA micoarrays to enable the determination of single nucleotide changes in DNA sequences and therefore provides an economical means of rapidly determining the entire sequence of a genome.

Selected References:

Gresham,G., Ruederfer, D., Pratt, S., Schacherer, J., Dunham, M., Botstein, D., Kruglyak, L. 9 March 2006, Genome-Wide Detection of Polymorphisms at Nucleotide Resolution with a Single DNA Microarray, www.sciencexpress.org,, page 1.

Patent protection is pending. For more information on Princeton University Invention # 06-2269 please contact:

                        Laurie Tzodikov

                        Office of Technology Licensing and Intellectual Property

Princeton University

                        4 New South Building

Princeton , NJ 08544-0036

                        (609) 258-7256

                        (609) 258-1159 fax

                        tzodikov@princeton.edu