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Published Online November 11, 2004
Science DOI: 10.1126/science.1103388

Reports

Submitted on July 29, 2004
Accepted on November 3, 2004

Global Identification of Human Transcribed Sequences with Genome Tiling Arrays

Paul Bertone 1, Viktor Stolc 2, Thomas E. Royce 3, Joel S. Rozowsky 3, Alexander E. Urban 1, Xiaowei Zhu 1, John L. Rinn 3, Waraporn Tongprasit 4, Manoj Samanta 5, Sherman Weissman 6, Mark Gerstein 3*, Michael Snyder 7*

1 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.
2 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA; Center for Nanotechnology, NASA Ames Research Center, Moffett Field, CA 94035, USA.
3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
4 Eloret Corporation, Sunnyvale, CA 94087, USA.
5 Center for Nanotechnology, NASA Ames Research Center, Moffett Field, CA 94035, USA.
6 Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
7 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.

* To whom correspondence should be addressed.
Mark Gerstein , E-mail: mark.gerstein{at}yale.edu
Michael Snyder , E-mail: michael.snyder{at}yale.edu

Elucidating the transcribed regions of the genome constitutes a fundamental aspect of human biology, yet this remains an outstanding problem. To comprehensively identify coding sequences, we constructed a series of high-density oligonucleotide tiling arrays representing sense and antisense strands of the entire nonrepetitive sequence of the human genome. Transcribed sequences were located across the genome via hybridization to complementary DNA samples, reverse-transcribed from polyadenylated RNA obtained from human liver tissue. In addition to identifying many known and predicted genes, we found 10,595 novel transcribed sequences not detected by other methods. A large fraction of these are located in intergenic regions distal from previously annotated genes and exhibit significant homology to other mammalian proteins.


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