Scientists Discover New Gene Associated with Crohn's Disease.

Applied Biosystems Genotyping Technologies Uncover New Support for Role of Abnormal Immune Response to Intestinal Bacteria in the Disease

FOSTER CITY, Calif. & KIEL, Germany -- Scientists have discovered another piece of the genetic puzzle that may predispose humans to Crohn's disease, a complex disorder characterized by chronic inflammation of the digestive tract. The findings may also suggest new strategies for treating this chronic, debilitating disease.

Researchers from the University Hospital of the Christian-Albrechts University in Kiel, Germany and Applied Biosystems (NYSE: ABI), an Applera Corporation Business, have identified and characterized a novel genetic variation in a gene not previously associated with the disorder that provides further evidence that an abnormal immune response to bacteria in the digestive tract may lead to the intestinal inflammation characteristic of the disease.

The results of the team's three-year collaboration will be published in the February issue of Nature Genetics.

The research team tested DNA samples from patients with Crohn's disease using the Applied Biosystems SNPlex[TM] Genotyping System, which employs pre-designed assays on the company's capillary electrophoresis DNA analysis platform. As part of the genotyping study, the team conducted a genome-wide association scan of approximately 20,000 "coding" genetic variants that are thought to produce functional changes at the protein level.

Among their findings, the researchers identified a protein-coding genetic variation (a single nucleotide polymorphism, or 'SNP') in the autophagy-related 16-like (ATG16L1) gene. Neither the ATG16L1 gene, nor this specific genetic variation, has been previously implicated in Crohn's disease. The ATGI6LI gene is part of the autophagosome biological pathway, which normal cells use to destroy harmful bacteria.

"With the discovery of APG16L1 as a new gene associated with Crohn's disease, we have demonstrated the power of a targeted, genome-wide investigation of coding SNPs," said Stefan Schreiber, M.D., Ph.D., Professor of Medicine at the Christian-Albrechts University in Kiel, Germany, and senior author of the study. "We also have discovered a further piece of evidence that highlights epithelial cells in the digestive tract and therefore a weakened barrier function as the most likely target for the underlying etiology of chronic inflammatory bowel disease."

"With further evidence that genetic factors may be compromising the defenses of the intestinal barrier in Crohn's disease, we believe pharmaceutical researchers have an opportunity to design new therapies that may address the root cause, not just the symptoms, of this chronic disease," added Francisco De La Vega, Ph.D., Scientific Fellow, Applied Biosystems, and a co-author of paper. "We plan to continue using this targeted approach with coding SNPs to study this and other complex diseases."

Applied Biosystems is providing access to the list of SNPs selected for this study at http://cSNP.appliedbiosystems.com/. Researchers can browse the SNP data and link to pre-designed assays for each genetic variation of interest. Over 3,000 of these SNPs were not previously available in the public domain and were discovered in the gene re-sequencing efforts of the Applera Genomics Initiative. As part of this publication, these novel variants also will be deposited in the NCBI's dbSNP database under submission handle "ABI" for perusal by the scientific community in other targeted association studies.

The study was selected by the editors of Nature Genetics for advance online publication and is available now to the journal's subscribers at http://dx.doi.org/10.1038/ng1954.

About Applera Corporation and Applied Biosystems

Applera Corporation consists of two operating groups. The Applied Biosystems Group serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Customers use these tools to analyze nucleic acids (DNA and RNA), small molecules, and proteins to make scientific discoveries and develop new pharmaceuticals. Applied Biosystems' products also serve the needs of some markets outside of life science research, which we refer to as "applied markets," such as the fields of: human identity testing (forensic and paternity testing); biosecurity, which refers to products needed in response to the threat of biological terrorism and other malicious, accidental, and natural biological dangers; and quality and safety testing, for example in food and the environment. Applied Biosystems is headquartered in Foster City, CA, and reported sales of over $1.9 billion during fiscal 2006. The Celera Group is primarily a molecular diagnostics business that is using proprietary genomics and proteomics discovery platforms to identify and validate novel diagnostic markers, and is developing diagnostic products based on these markers. Celera maintains a strategic alliance with Abbott Laboratories for the development and commercialization of molecular, or nucleic acid-based, diagnostic products, and it is also developing new diagnostic products outside of this alliance. Through its genomics and proteomics research efforts, Celera is also discovering and validating therapeutic targets, and it is seeking to develop therapeutic products based on these discovered targets through strategic partnerships. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.applera.com, or by telephoning 800.762.6923. Information about Applied Biosystems is available at http://www.appliedbiosystems.com/.

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