New Affymetrix Microarray Sequences Complete Mitochondrial Genome in a Single 48 Hour Experiment.

SANTA CLARA, Calif. -- GeneChip(R) Human Mitochondrial Resequencing Array 2.0 Enables Researchers to Identify Genetic Variations Associated with Diseases, Forensics, Population Studies or Stem Cells 

Affymetrix Inc. (Nasdaq:AFFX) today announced the launch of the GeneChip(R) Human Mitochondrial Resequencing Array 2.0, enabling researchers to analyze the entire sequence of the mitochondrial genome in a single 48 hour experiment. The new microarray interrogates all 16,500 bases of the human mitochondrial genome with only three polymerase chain reactions (PCR), providing scientists with the most efficient and cost-effective method for detecting variants associated with genetic disease, forensics, population studies or stem cells.

"We get sequence data from the Affymetrix GeneChip Human Mitochondrial Array about ten times faster than we do with conventional methods," said Bert Smeets, Ph.D., associate professor of Genetics at Maastricht University. "Using the array in our studies of complex mitochondrial disease, we've discovered five known pathogenic mutations and more than 70 previously unknown genetic variations in patients, which allow us to explain the pathology in about 25 percent of the patients. The whole-genome approach is helping us to understand this disease at a level of detail never before possible."

"There's an obvious increase in the number of mutations that can be detected with the second generation GeneChip mitochondrial array," said Joseph Califano, M.D., associate professor of otolaryngology at Johns Hopkins University. "To date, we've sequenced about 85 head-neck tumors with matching white blood cell DNA from those patients. So far, we've found a pretty impressive somatic mutation rate of close to 50 percent in these tumors."

"The robust Affymetrix GeneChip Human Mitochondrial Resequencing Array 2.0 provides a complete picture of variation in the mitochondrial genome, while significantly reducing the time, labor and cost involved in sample preparation," said Greg Yap, vice president of DNA Products at Affymetrix. "We anticipate that access to complete sequence information for mitochondria on a single array will lead to new discoveries in a wide range of fields including disease genetics, forensic identification and population genetics."

Array Applications

Disease Genetics

Mutations of mitochondrial DNA can lead to a number of illnesses including neurodegenerative and other degenerative disorders, sudden infant death syndrome and multiple cancer types. The Affymetrix mitochondrial array provides complete sequence information and enables the detection of both known and novel mutations in the mitochondrial genome associated with these complex diseases.

Forensic Identification

Mitochondrial DNA, which is more abundant and stable than genomic DNA, is widely used in forensic applications when the genomic DNA is too scarce or too degraded for standard analysis. Analysis of the mitochondrial hypervariable regions (HVI and HVII) has traditionally been used to match criminals to crime scenes and identify the remains of mass disaster victims. The Affymetrix mitochondrial array captures genetic variation at every base and enables the discrimination between samples that can not be distinguished by only analyzing the HVI and HVII regions.

Population Genetics

Mitochondrial DNA is passed from mother to child and is useful in tracking the migration of populations throughout history. Researchers that want to study human evolution can use the Affymetrix mitochondrial array to compare the genetic variation among different populations.

Stem-cell Integrity

In September 2005, a research group led by scientists at Johns Hopkins School of Medicine and the National Institutes of Health used the Affymetrix' Human Mitochondrial Resequencing Array 2.0 to discover that at least two of the stem cell lines approved for federally-funded research have developed mutations in their mitochondrial DNA. The scientists found the mutations by analyzing the entire mitochondrial genome sequence from cells that had been grown in the laboratory for dozens of generations. Their results have raised concerns about the use of the remaining cell lines that have been approved for federally-funded research.

Array Design

The GeneChip Human Mitochondrial Array 2.0 interrogates the entire 16kb mitochondrial genome and enables the detection of known and novel mutations. The sequence was selected from the MITOMAP Revised Cambridge Reference Sequence (RCRS) database. The array also contains additional tiling for most of the common variants in the HVI and HVII regions selected from the FBI database. The robust assay amplifies the entire genome in only three PCR reactions, dramatically reducing the cost and time involved in traditional sequencing. Furthermore, the unparalleled sensitivity of this assay allows for detection of heteroplasmy.

Array System

The Affymetrix mitochondrial array is built on the same GeneChip technology that has been the industry standard in microarray research for the past decade. The mitochondrial system launched today includes:

--GeneChip Human Mitochondrial Resequencing Array 2.0

--GeneChip Resequencing Assay Kit

--GeneChip Operating Software (GCOS) 1.4 and GeneChip Sequence Analysis Software (GSEQ) 4.0

For more information on the Affymetrix GeneChip Human Mitochondrial Resequencing Array 2.0, please visit the company's website at: http://www.affymetrix.com/products/arrays/specific/mito_reseq_2.affx.

Further Reading

Scientific Publications

--Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN, Noaksson K, Hyllner J, Schulz TC, Zeng X, Freed WJ, Colman A, Sartipy P, Matsui SI, Carpenter M, Gazdar AF, Rao M, Chakravarti A. Genomic alterations in cultured human embryonic stem cells Nature Genet 2005; (Sept 4th online edition).

--Maitra A, Cohen Y, Gillespie SE, Mambo E, Fukushima N, Hoque MO, Shah N, Goggins M, Califano J, Sidransky D, Chakravarti A. The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection. Genome Res 2004; 14(5):812-9.

--Kim MM, Clinger JD, Masayesva BG, Ha PK, Zahurak ML, Westra WH, Califano JA. Mitochondrial DNA quantity increases with histopathologic grade in premalignant and malignant head and neck lesions. Clin Cancer Res. 2004; 10(24):8512-5.

--Petros JA, Parrish AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM, Flanders WD, Hosseini SH, Marshall FF, Wallace DC. mtDNA mutations increase tumorigenicity in prostate cancer. PNAS 2005; 102(3):719-24.

--Stephens P, Edkins S, Davies H et al. A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer. Nat Genet 2005; 37(6):590-2.

AMB Stories

--Califano, Joseph. Interview with Amanda Parrish. "Mitochondrial Genome Scan Finds Cancer Mutations in Saliva DNA Samples." Affymetrix Microarray Bulletin. 2005 October 1; 1(4): 1, 17-19.

--Chakravarti, Aravinda. Interview with Anirban Maitra and Mahendra Rao. "Human Embryonic Stem Cell Study Uncovers Genetic Mutations in Federally-approved Lines." Affymetrix Microarray Bulletin. 2005 September 1; 1(3): 1-4.

--Jakupciak, John. Interview with Ryan Parr. "New Microarray Improves Sensitivity of Cancer Detection by Pinpointing Small Changes in Mitochondrial DNA." Affymetrix Microarray Bulletin. 2005 October 1; 1(4): 23-26.

--Kato, Tadafumi. Interview with Ryota Hashimoto. "Microarrays Provide Fast and Sensitive Genetic Fingerprint for Forensic Investigations." Affymetrix Microarray Bulletin. 2005 October 1; 1(4): 32-34.

--Maitra, Anirban. Interview with Amanda Baumann. "Microarray Sequencing of Mitochondrial Genome Uncovers New Clues for Cancer Detection." Affymetrix Microarray Bulletin. 2005 July 1; 1(2): 1, 13-16.

--Smeets, Hubertus. Interview with Amanda Parrish. "Genome Scan Finds Mutations in at least a Quarter of Patients with Complex Mitochondrial Diseases." Affymetrix Microarray Bulletin. 2005 October 1; 1(4): 20-23.

--Strausbaugh, Linda. Interview with Martin Buoncristiani. "Genome Scan Finds Mutations in at least a Quarter of Patients with Complex Mitochondrial Diseases." Affymetrix Microarray Bulletin. 2005 October 1; 1(4): 27-31.

AMB Symposia Series:

--Smeets, Hubertus. Nov 16, 2005. Resequencing Microarrays and Complex Mitochondrial Disease. Seminar presented at the Affymetrix Microarray Bulletin Fall Symposia Series.

--Strausbaugh, Linda. Dec 7, 2005. Evaluation of the GeneChip Mitochondrial Resequencing Array for Forensic Application. Seminar presented at the Affymetrix Microarray Bulletin Fall Symposia Series.

About Affymetrix

Affymetrix scientists invented the world's first high-density 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 1,300 systems have been installed around the world and nearly 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 analyzing the relationship between genetics and health. Affymetrix is headquartered in Santa Clara, Calif. with subsidiaries in Europe and Asia, as well as manufacturing facilities in Sacramento, Calif. and Bedford, Mass. The company has about 1,000 employees worldwide. For more information about Affymetrix, please visit the company's Web site at www.affymetrix.com.

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