Abstract

In this research we first propose to further develop the use of spatially defined arrays of oligonucleotide probes for sequence checking and de novo sequencing. Second, we will implement the technology in a pilot scale sequencing project. To accomplish this we will use the integrated chips, instrumentation, and software platform as defined in project 2 to explore: * Assays that discriminate perfect matches from mismatches. * Prediction of the hybridization intensities of probe-target combinations to aid in target specific array design. * Data analysis and sequence reconstruction algorithms using hybridization data. * The effectiveness of the assays in a pilot scale sequencing project. Successful completion of this work could lead to sequencing instrumentation that will provide order of magnitude improvements in DNA sequencing productivity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Program Projects (P01)
Project #
5P01HG001323-02
Application #
5213045
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Lee, Albert; Henras, Anthony K; Chanfreau, Guillaume (2005) Multiple RNA surveillance pathways limit aberrant expression of iron uptake mRNAs and prevent iron toxicity in S. cerevisiae. Mol Cell 19:39-51
Danin-Kreiselman, Michal; Lee, Chrissie Young; Chanfreau, Guillaume (2003) RNAse III-mediated degradation of unspliced pre-mRNAs and lariat introns. Mol Cell 11:1279-89
Patti, Mary Elizabeth; Butte, Atul J; Crunkhorn, Sarah et al. (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100:8466-71
Zheng, Z; Venkatapathy, S; Rao, G et al. (2002) Expression profiling of B cell chronic lymphocytic leukemia suggests deficient CD1-mediated immunity, polarized cytokine response, altered adhesion and increased intracellular protein transport and processing of leukemic cells. Leukemia 16:2429-37
Schulze, A; Lehmann, K; Jefferies, H B et al. (2001) Analysis of the transcriptional program induced by Raf in epithelial cells. Genes Dev 15:981-94
Soulez, M; Parker, M G (2001) Identification of novel oestrogen receptor target genes in human ZR75-1 breast cancer cells by expression profiling. J Mol Endocrinol 27:259-74
Nadler, S T; Stoehr, J P; Schueler, K L et al. (2000) The expression of adipogenic genes is decreased in obesity and diabetes mellitus. Proc Natl Acad Sci U S A 97:11371-6
Hacia, J G; Fan, J B; Ryder, O et al. (1999) Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays. Nat Genet 22:164-7
Gentalen, E; Chee, M (1999) A novel method for determining linkage between DNA sequences: hybridization to paired probe arrays. Nucleic Acids Res 27:1485-91
Sapolsky, R J; Hsie, L; Berno, A et al. (1999) High-throughput polymorphism screening and genotyping with high-density oligonucleotide arrays. Genet Anal 14:187-92

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