New Evidence for Whole Genome Linkage in Bipolar Disorder Affymetrix GeneChip(R) Mapping 10K Array Allows for Discovery of Two New Genetic Loci Previously Undetected by Microsatellite Analysis SANTA CLARA, Calif., March 31 /PRNewswire-FirstCall/ -- Affymetrix, Inc., announced today that a team of researchers from Upstate Medical University, the Department of Veterans Affairs (VA), the University of Coimbra and the Broad and Whitehead Institutes discovered new evidence for whole genome linkage in bipolar disorder. The study on this complex psychiatric disease is one of the first published using the GeneChip(R) Mapping 10K Array, a higher resolution, easier and faster alternative to microsatellites for linkage and linkage disequilibrium analyses. (For an interactive version of this press release with additional information, please go to http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=AFFX&script=400 and click on the release title) The study, which has been accepted for publication in the May 2004 issue of the American Journal of Human Genetics, identified two new loci on chromosomes 6 and 11 that show evidence for linkage in this complex disorder. Both loci contain genes that appear to play a major role in brain function, according to the paper. The chromosome 6 finding replicated previous findings by the National Institutes of Health (NIH), an encouraging step in a disease which often yields conflicting findings and un-reproducible findings from study to study. "This long-term genetic population study has the potential of helping us understand the importance of a variety of genetic factors on bipolar disorder and other psychotic disorders," explained Carlos and Michele Pato from Upstate Medical University and the Washington, D.C. Veterans Affairs Medical Center. "The ability to achieve genome-wide significance for linkage in this population was clearly enhanced by the far more complete linkage information possible with the 10K. We are looking forward to important collaborative efforts with others in the field to further explore these findings." The study was performed in two parts. In the first part, the research team analyzed 12 families with both microsatellites and the Mapping 10K Array. The resultsshowed a high degree of corresponding linkage findings for most chromosomes using both approaches. More importantly, however, analysis with the Mapping 10K Array showed evidence for significant genome-wide linkage on two additional chromosomes in locations where the marker density and information content of microsatellite-based assays were very low. In the second part of the study, the analysis was expanded to include 25 families, all of which were assayed with the Mapping 10K. These results demonstrated even greater evidence for genome-wide significance, with linkage mapping to chromosomal region 6q22. This discovery, which replicated findings that took NIH researchers in bipolar disorder several years using hundreds of families, was arrived atin less than 5 months at nearly one tenth the cost of the previous microsatellite genome scan. "Using the 10K clearly revealed gaps in the coverage and the information content of the traditional microsatellite-based assay," said Frank Middleton of Upstate Medical University. "It was exactly in those gaps where the new significant signals were found. We're very encouraged by the results, by the close correlation with the NIH findings, and by how fast and accurately we were able to do the study using the 10K Array." In planned follow up studies, the research team will greatly expand the number of affected individuals studied, genotyping all families within the geographic area with histories of bipolar disorder using a similar whole genome approach. In addition, the investigators will greatly increase the number of SNPs assayed in follow up analysis of the 6q22 linkage peaks and pool their results with data from the NIH showing a similar result. The study was funded by the National Institute of Mental Health (NIMH), the VA, the National Alliance for Research on Schizophrenia and Depression (NARSAD), and the Fundacao para a Ciencia e a Tecnologia (FCT) in Portugal. The Mapping 10K Array brings whole genome SNP analysis to the benchtop by combining an innovative, scalable assay with a proven information platform. All 10,000 genotypes are generated in a single experiment, allowing more rapid discovery of genomic regions linked to disease. The platform allows for automated genotype calling andproduces the highest physical and genetic resolution available for family linkage studies in inherited disease. Additional reported applications of this technology include cancer genetics (chromosomal amplification, deletion and loss of heterozygosity)and population genetics. About Affymetrix: Affymetrix is a pioneer in creating breakthrough tools that are driving the genomic revolution. By applying the principles of semiconductor technology to the life sciences, Affymetrix develops and commercializes systems that enable scientists to improve quality of life. The Company's customers include pharmaceutical, biotechnology, agrichemical, diagnostics and consumer products companies as well as academic, government and other non-profit research institutes. Affymetrix offers an expanding portfolio of integrated products and services, including its integrated GeneChip brand platform, to address growing markets focused on understanding the relationship between genes and human health. Additional information on Affymetrix can be found at http://www.affymetrix.com/. 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, market acceptance (including uncertainties relating to product development and market acceptance of the GeneChip(R) Mapping 10K Array), 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 riskfactors are discussed in Affymetrix' Form 10-K for the year ended December 31, 2003 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, Associate Director, Public Relations, +1-408-731-5791, or ; or investors, Doug Farrell, Vice President, Investor Relations, +1-408-731-5285, or , both of Affymetrix, Inc. Web site: http://www.affymetrix.com/

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