AFFX Affymetrix, Inc.

New Study from Affymetrix Laboratories Points to Changing View of How Genome Works Any single base in genome can be transcribed into many different RNA sequences, most of which never leave the nucleus SANTA CLARA, Calif., March 24 /PRNewswire-FirstCall/ -- Scientists at Affymetrix, Inc. (NASDAQ:AFFX) reported today in Science magazine online that they have completed a high-resolution scan of structure and function for nearly 30 percent of the human genome sequence. In collaboration with the National Cancer Institute, the research team used high-density GeneChip(R) microarrays to study every fifth base, on average, of 10 human chromosomes; they found that thousands of regions of the genome are transcribed into overlapping RNA sequences and those sequences are separated by regions in which RNA is transcribed more scarcely. All of the data is freely available at http://transcriptome.affymetrix.com/publication/transcriptome_10chromosomes and http://cgap.nci.nih.gov/Info/2005.1 "The findings of this study compel us to reconsider how the genome is organized and regulated," said Thomas Gingeras, Vice President for Biological Research at Affymetrix and senior author of the Science manuscript. "These data point us toward two critical and exciting questions: What are the functions of these previously unannotated transcripts and what are the regulation schemes that orchestrate such complex assemblies of transcription? It seems certain that this is not the genome we learned about while in school." In the "traditional" view of the human genome, there are about 26,000 genes used to make proteins that ultimately control the structure and function of every cell in the body. Most disease research has focused on studying these protein-coding genes, even though they make up only about two percent of the human genome sequence. The new study by Gingeras' team did not make any assumption of what parts of the genome might or might not be important to human biology. They used new Affymetrix tiling microarrays and unique biochemical tests to scan the sequence of 10 human chromosomes -- one third of the human genome sequence -- and found that roughly 15 percent of the DNA sequence analyzed was transcribed; most sites of transcription were not located in areas associated with protein-coding genes. The team found many diverse kinds of RNAs transcribed from distinct regions of the genome, creating a complex pool of overlapping transcription. While the team validated many known protein-coding transcripts that contribute to this complex pool, they also discovered that: -- Seventy-five percent of all of the RNA that were exclusively found in the nucleus had not been previously detected. -- Any single base in the genome can be transcribed into several different transcripts with different, but overlapping sequences. Often, transcripts from one strand of DNA can share parts of their sequence with overlapping transcripts from the same strand or even from the opposite strand (antisense). -- Transcripts missing a run of adenosine nucleotides (non-polyA) at the tail-end were twice as common as the more well-studied RNAs that have this sequence. Most transcripts derived from the sparsely transcribed regions between centers of dense transcription are non-polyA transcripts. This study focused on an in depth scan of 10 chromosomes; however, Affymetrix has developed tiling microarrays that cover all human chromosomes. GeneChip tiling microarrays have been used by Gingeras and his collaborators, as well as the NHGRI publicly funded ENCODE project, to study the human genome in an unbiased fashion -- including regions that have historically been termed coding and non-coding. Affymetrix is now beginning to commercialize tiling microarrays to give the research community the ability to perform these types of unbiased studies as well. By focusing research beyond the parts of the genome that have been traditionally studied, scientists hope to discover new drug targets, new biomarkers, and a better understanding of disease mechanism. This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract number N01-CO-12400. About Tiling Arrays: Affymetrix "tiling" arrays mark a shift in the way microarrays are designed and interpreted. By using a neutral approach to array design, tiling arrays include all non-repetitive sequence from a given genome, not just the hand-selected regions that were previously thought to be important. With the inclusion of all genomic sequences, microarrays can now be used as a discovery tool to generate annotations and discover new transcripts. In late 2005, Affymetrix plans to launch high-resolution tiling arrays for the entire human genome and several model organisms, including Drosophila, Arabidopsis, S. cerevisiae and S. pombe. Further Information: Using GeneChip(R) technology to study all human transcripts (Transcriptome) -- http://www.affymetrix.com/transcriptome/ Using Affymetrix tiling arrays in the ENCODE project -- http://www.affymetrix.com/products/arrays/specific/encode.affx Using tiling arrays to discover new transcripts in Arabidopsis -- http://www.affymetrix.com/community/wayahead/beyond_arabidopsis.affx Using tiling arrays to map new human transcription factor binding sites -- http://www.affymetrix.com/community/wayahead/exploring_human_genome.affx About Affymetrix Affymetrix scientists invented the world's first microarray in 1989 and began selling the first commercial microarray in 1994. Since then, Affymetrix GeneChip(R) technology has become the industry standard in molecular biology research. Affymetrix technology is used by the world's top pharmaceutical, diagnostic and biotechnology companies as well as leading academic, government and not-for-profit research institutes. More than 1,200 systems have been shipped around the world and over 3,000 peer-reviewed papers have been published using the technology. Affymetrix' patented photolithographic manufacturing process provides the most information capacity available today on an array, enabling researchers to use a whole-genome approach to analyze the relationship between genetics and health. Affymetrix is headquartered in Santa Clara, Calif., with manufacturing facilities in Sacramento, Calif., and Bedford, Mass. The company maintains important sales and marketing operations in Europe and Asia and has about 900 employees worldwide. All statements in this press release that are not historical are "forward- looking statements" within the meaning of Section 21E of the Securities Exchange Act as amended, including statements regarding Affymetrix' "expectations," "beliefs," "hopes," "intentions," "strategies" or the like. Such statements are subject to risks and uncertainties that could cause actual results to differ materially for Affymetrix from those projected, including, but not limited to risks of the Company's ability to achieve and sustain higher levels of revenue, higher gross margins, reduced operating expenses, uncertainties relating to technological approaches, manufacturing, product development (including uncertainties relating to the use of the tiling arrays and outcome of research discussed in this press release), personnel retention, uncertainties related to cost and pricing of Affymetrix products, dependence on collaborative partners, uncertainties relating to sole source suppliers, uncertainties relating to FDA and other regulatory approvals, competition, risks relating to intellectual property of others and the uncertainties of patent protection and litigation. These and other risk factors are discussed in Affymetrix' Form 10-K for the year ended December 31, 2004 and other SEC reports, including its Quarterly Reports on Form 10-Q for subsequent quarterly periods. Affymetrix expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Affymetrix' expectations with regard thereto or any change in events, conditions, or circumstances on which any such statements are based. NOTE: Affymetrix, the Affymetrix logo, and GeneChip are registered trademarks owned or used by Affymetrix, Inc. DATASOURCE: Affymetrix, Inc. CONTACT: Media: Wes Conard, Director, Public Relations, +1-408-731-5791, or, Investors: Doug Farrell, Vice President, Investor Relations, +1-408-731-5285, both of Affymetrix Web site: http://www.affymetrix.com/

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