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Celera and Collaborators Identify Gene Variants Predicting Susceptibility to, and Severity of, Rheumatoid Arthritis
Findings from four independent studies involving more than 4,700 individuals likely to improve identification of high risk individuals enabling earlier therapeutic intervention

ROCKVILLE, MD and ALAMEDA,CA - September 17, 2007

Celera (NYSE:CRA), an Applera Corporation business, and its collaborators at the Leiden University Medical Centre in the Netherlands and the Karolinska Institute in Sweden, today announced the publication of a paper describing novel variants in the TRAF1/C5 gene region that predict individual susceptibility to, and severity of, rheumatoid arthritis (RA). Compared with non-carriers, carriers of the risk variants (about 65-70 percent of the general population) had an approximate 37 percent increased risk for developing RA. The paper is scheduled to appear in the September 2007 edition of the Public Library of Science (Medicine), and is currently available on the journal’s website at http://medicine.plosjournals.org.

Celera and its collaborators evaluated DNA samples from more than 4,700 individuals to compare patterns of genetic variation in those with rheumatoid arthritis to those without the disease. TRAF1/C5 was confirmed in four independent research studies (two in the Netherlands and one each in Sweden and the U.S.), and was responsible for about 6 percent of the risk for this disease. Located on chromosome 9, TRAF1 encodes a protein that is a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) protein family, which associates with, and mediates the signal transduction from, various receptors of the TNF superfamily. C5 encodes a key component of the complement system and activation of the complement system has been implicated in the pathogenesis of many inflammatory diseases.

Celera first confirmed that this region was associated with RA in 2006, which was preceded by its other discovery of PTPN22, now replicated by multiple laboratories, as a genetic contributor to the etiology of RA. An association of this region with RA has also been reported by another group independently . Another major contributor to RA risk is human leukocyte antigen (HLA). The discovery of TRAF1/C5 provides a valuable addition to HLA and PTPN22, which contribute approximately 30 percent and 12 percent respectively, in explaining a genetic contribution to RA.

“Celera is currently determining the clinical utility of these gene variants and integrating them with other genetic markers for early diagnosis, prediction of disease severity, and possibly a patient’s response to various therapies in rheumatoid arthritis,” said Thomas White, Ph.D., chief scientific officer at Celera. “Our goal at Celera is to incorporate these discoveries into new diagnostic tests, and initial data suggest an association with increased disease progression. From a functional perspective, it is interesting that TRAF1 is likely involved in TNF signaling, and we are looking to identify the role it may play in predicting the efficacy of drugs that work via this pathway.”

“The determinants of the severity of rheumatoid arthritis are complex, but scientifically rigorous studies such as this one provide sound evidence of a major genetic component,” said Tom Huizinga, M.D., Ph.D. Head of the Department of Rheumatology, Leiden University Medical Centre, a collaborator and a co-author of the study. “Eventually, building on these studies, physicians and patients should have access to blood tests that can assess each individual’s respective genetic risk of developing this disease, which in turn will enable earlier and more appropriate therapeutic intervention.”

Dr Huizinga added, “Currently, we are able to stop joint destruction and disease progression in most patients with high doses of immunosuppression drugs. However, these regimens have sufficiently large side effects that most physicians and their patients decide to start treatment with relatively mild drugs. The challenge in rheumatology now is the development of a means to determine those patients at greater risk for this disease and in need of more intensive treatment strategies. These genetic discoveries are making substantial headway in addressing this challenge.”

About Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory disease in which the body’s natural immune system does not function properly and attacks healthy joint tissues, including the lining of the joints, or synovium. This can lead to joint destruction and results in pain, stiffness, swelling and loss of motion in the joints. The age of onset for RA is usually between 30 and 50 and the disease is two to three times more common in women than men. It is one of the most common autoimmune diseases, affecting approximately 1 percent of the population worldwide and its prevalence is expected to increase as the population ages. The exact cause of RA is not yet fully understood.

Physicians currently diagnose RA based on the overall pattern of symptoms, medical history, physical exam, X-rays and lab tests including a test for rheumatoid factor. Rheumatoid factor is an antibody found in the blood of approximately 70-80% of adults with RA. However, it is also seen in other conditions besides RA and in many healthy individuals.

About Applera Corporation and Celera
Applera Corporation consists of two operating groups. Celera 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 as well as other known markers. Celera maintains a strategic alliance with Abbott 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 strategic partnerships to develop therapeutic products based on these discovered targets. 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 nearly $2.1 billion during fiscal 2007. 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 Celera is available at http://www.celera.com.

Applera Forward-Looking Statement
Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe," "expect," "plan," and "should," among others. These forward-looking statements are based on Applera Corporation’s current expectations. The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Applera notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to: (1) uncertainty in obtaining intellectual property protection for inventions made by Celera; (2) unproven ability of Celera to discover, develop, and commercialize diagnostic products based on findings from its disease association studies; (3) unproven use of genomics information to develop diagnostic products; (4) uncertainty as to whether Celera will be able to obtain any required regulatory approval of its diagnostic products; (5) uncertainty of market acceptance of its products, including the risk that its products will not be competitive with products offered by other companies, or that users will not be entitled to receive adequate reimbursement for its products from third party payors such as private insurance companies and government insurance plans; and (6) other factors that might be described from time to time in Applera’s filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Applera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

Copyright© 2007. Applera Corporation. All rights reserved. Applera, Applied Biosystems and Celera are registered trademarks of Applera Corporation or its subsidiaries in the US and certain other countries.

Contact:
David Speechly, Ph.D.
tel.: 510.749.1853
email: david.speechly@celera.com

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