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 olymorphisms 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