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Microarray Sequence Capture Speeds Large-Scale Resequencing of Targeted Genomic Regions
Date:10/15/2007

MADISON, Wis., Oct. 15 /PRNewswire/ -- Researchers at Baylor College of Medicine and Roche NimbleGen Inc., a fully integrated part of Roche Applied Science, today have published details of a highly efficient and cost-effective method for capturing targeted regions of the genome via NimbleChip(TM) microarrays in preparation for high-throughput 454 Sequencing(TM). The technology, called "sequence capture," enables fast and accurate enrichment of thousands of selected genomic regions, either contiguous or dispersed, such as segments of chromosomes or all genes or exons. The study, entitled "Direct Selection of Human Genomic Loci by Microarray Hybridization," appears online (ahead of print) in the journal Nature Methods(1).

In light of the success of the current sequence capture technology, Baylor's Human Genome Sequencing Center (HGSC) has signed on as an early access customer to Roche NimbleGen's sequence capture technology. As presented on October 10, 2007, at the J. Craig Venter Institute's Genomes, Medicine, and the Environment (GME) conference, Roche NimbleGen and 454 Life Sciences, working with Dr. Richard Gibbs, professor and Director of the HGSC, will create a whole-genome human exome (all exons) microarray, with the goal of resequencing the entire human exome.

Resequencing of genes or other genomic regions of interest is a key step in detecting mutations associated with various complex human diseases, such as cancer, asthma and heart disease. The predominant method for selection of specific genomic regions for resequencing has primarily relied on PCR (polymerase chain reaction) to enrich for specific DNA fragments. However, PCR is limited in the length of sequence it can amplify, is difficult to scale or multiplex for the enrichment of thousands of fragments, and has limited performance in the repetitive regions typical of complex genomes, such as human. The sequence capture microarray technology bridges the gap between next-generation DNA sequencing technology and current sample preparation methods by providing an adaptable, massively parallel method for selective enrichment of genomic regions of interest. Roche NimbleGen's sequence capture technology enables high-performance targeting of thousands of specific genes or loci using a single microarray hybridization-based enrichment process. The Baylor study(1) used Roche's Genome Sequencer FLX(TM) System to quickly and affordably sequence the enriched genomic regions for downstream analysis. 454 Sequencing technology is ideal for this targeted sequencing approach because of its long read lengths and highly accurate reads.

"This new technology will replace polymerase chain reaction (PCR) for many purposes," said Gibbs. "If the aim is to sequence a whole genome for everybody, this is a huge step in that direction."

The Nature Methods paper published by Baylor(1) demonstrates that the sequence capture process is simpler, more accurate, more efficient and more cost-effective than the multiplex PCR that was previously used to prepare genomic samples for sequencing. In one experiment, more than 6,700 exons (the part of the genetic code that together form genes), were enriched and analyzed, as well as contiguous genomic regions of up to 5 million bases. Using the old technology this would have taken at least six months.

"We're delighted to have an opportunity to collaborate with scientists at Baylor HGSC on the development of this breakthrough technology," said Dr. Stan Rose, President of Roche NimbleGen. "The combination of these two Roche technologies-NimbleGen and 454-has the potential to transform the market for DNA sequence analysis."

Roche NimbleGen is a leading innovator, manufacturer, and supplier of a proprietary suite of DNA microarrays, consumables, instruments, and services. Roche NimbleGen uniquely produces high-density arrays of long oligo probes that provide greater information content and higher data quality necessary for studying the full diversity of genomic and epigenomic variation. The improved performance is made possible by Roche NimbleGen's proprietary Maskless Array Synthesis (MAS) technology, which uses digital light processing and rapid, high-yield photochemistry to synthesize long oligo, high-density DNA microarrays with extreme flexibility. For more information about Roche NimbleGen, please visit the company's website at http://www.nimblegen.com.

454 Life Sciences develops and commercializes the innovative Genome Sequencer(TM) system for ultra-high-throughput DNA sequencing. Specific applications include de novo sequencing and re-sequencing of whole genomes, metagenomics, RNA analysis, and targeted sequencing of DNA regions of interest. The hallmarks of 454 Sequencing(TM) are its simple, unbiased sample preparation and long, highly accurate sequence reads, including paired reads. 454 Sequencing technology has enabled many peer-reviewed studies in diverse research fields such as: cancer research, infectious diseases research, drug discovery, marine biology, anthropology, paleontology, and many more.

For additional information, please visit http://www.454.com.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolic disorders and diseases of the central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invests approximately 7 billion Swiss francs a year in R&D. Worldwide, the Group employs about 75,000 people. Additional information is available on the Internet at http://www.roche.com.

(1) Albert TJ, Molla MN, Muzny DM, Nazareth L, Wheeler D, Song X, Richmond TA, Middle CM, Rodesch MJ, Packard CJ, Weinstock GM, and Gibbs RA. 2007. Direct selection of human genomic loci by microarray hybridization. Nat Meth. Published online 14 October 2007. (DOI:10.1038/NMETH1111)

For more information, please contact

Roche NimbleGen, Inc.

Joleen Rau

Sr. Director, Marketing Communications

Phone (608) 218-7623

Email: jrau@nimblegen.com


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SOURCE Roche NimbleGen, Inc.
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