We have developed a new ink-jet technology approach to the synthesis of DNA fragments (oligonucleotides) on glass or silicon chips. These DNA chips provide the potential opportunity to analyze thousands or even tens of thousands of expressed genes simultaneously by molecular complimentarity or hybridization. Thus, for example, the differences in gene expression patterns between normal and cancer cells can readily be analyzed. These DNA chips also afford the opportunity to readily analyze the most widespread genetic marker scattered across human chromosomes, single base substitutions. Thus, an inexpensive, rapid and comprehensive approach to genetic mapping may be possible. To realize the enormous potential of oligonucleotide chips, we propose to: 1) characterize the quality of the oligonucleotides synthesized by the ink-jet technology, 2) use yeast as a model system to explore how the expression patterns of 6,000 genes operating as systems under varying conditions can be quantitated, and 3) use this technology to develop a rapid and comprehensive typing system for the highly polymorphic human transplantation antigen locus, HLA-B.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG001713-03
Application #
2889685
Study Section
Special Emphasis Panel (ZHG1-HGR-N (O1))
Program Officer
Feingold, Elise A
Project Start
1997-09-30
Project End
2000-03-31
Budget Start
1999-08-09
Budget End
2000-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Lausted, Christopher; Dahl, Timothy; Warren, Charles et al. (2004) POSaM: a fast, flexible, open-source, inkjet oligonucleotide synthesizer and microarrayer. Genome Biol 5:R58
Zong, Q; Schummer, M; Hood, L et al. (1999) Messenger RNA translation state: the second dimension of high-throughput expression screening. Proc Natl Acad Sci U S A 96:10632-6
Schummer, M; Ng, W V; Bumgarner, R E et al. (1999) Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene 238:375-85