BRANFORD, Conn., Sept. 27, 2007 - 454 Life Sciences, a Roche company, in collaboration with Yale University researchers today announced that they have developed a method, using the company's Genome Sequencer system, to identify significant human genetic variability with an unprecedented level of detail. The new method enables researchers to analyze genome-wide structural variations (SV), the gross changes to the genetic code much faster and economically than existing techniques. The study, entitled "Paired-End Mapping Reveals Extensive Genomic Structural Variation in Humans," appears online (ahead of print) today in the journal Science.
Previous studies of human genomic variation tended to look at changes called single nucleotide polymorphism, variations that involve just one nucleotide, commonly referred to as SNP. However, the study published today suggests that structural variation is responsible for a larger number of differences between the genomes of two individuals than SNPs. Furthermore, structural variation may have notable physical effects on an individual. The role that SV plays in human variability has not been well understood because of cost-prohibitive and imprecise technology used in previous research. The novel approach described today in Science, called Paired End Mapping (PEM), used 454 Sequencing to comprehensively study SV at an unmatched level of precision, detecting most of the structural variation in the human genome.
"454 Sequencing enabled us to efficiently identify over 1000 structural variations in two individuals. Our study demonstrates that a large number of SVs are present in the human population and that SV plays a greater role in genetic diversity than SNP," explained Michael Snyder, PhD., senior author and Lewis B. Cullman Professor of Molecular, Cellular and Developmental Biology and Professor of Molecular Biophysics and Biochemistry; Director of the Yale Center for Genomics and Proteomics. "The widespread occurrence of structural variation and the observation that many genes are affected, suggests that SV is likely to be a major form of human variation. It will be essential to incorporate SV detection in human genome sequencing projects."
Although SVs were found throughout the genome, researchers found that many SVs are concentrated in specific regions or "hot spots". Several of these "hot-spots" are regions of the genome known to correlate to some genetic diseases such as Velocardiofacial Syndrome, and Williams-Beuren Syndrome. Furthermore, structural variation may affect gene function by altering the frequency of a given gene, changing its structure, or alter how the gene is regulated.
"454 Sequencing can generate hundreds of thousands of long read pairs that are unique within the human genome to quickly and accurately determine genomic variations," explained Michael Egholm, Ph.D., co-author of the study and vice president of research and development at 454 Life Sciences. "This highly accurate study of human genomic structural variation along with the recently sequenced genome of Jim Watson confirms that 454 Sequencing is the first affordable technology to offer a comprehensive view of the human genome."
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, metabolism and 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 employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Roche's Diagnostics Division offers a uniquely broad product portfolio and supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories world-wide. For further information, please visit our website at www.roche.com.
454 Life Sciences Corporation develops and commercializes novel instrumentation for high-throughput DNA sequencing. Specific applications include whole-genome sequencing, RNA analysis and ultra-deep sequencing of target genes. The hallmarks of 454 Sequencing™ are its simple, unbiased sample preparation and massively parallel sequencing, which makes large-scale scientific projects feasible and more affordable. 454 Sequencing and the Genome Sequencer 20 System won The Wall Street Journal's top Innovation Award in 2005 and received an R&D 100 Editor's Choice Award as one of the most technologically significant products in 2006. The 454 Sequencing Center offers sequencing services directly to customers on a fee for service basis. Genome Sequencer systems are distributed by Roche Applied Science. 454 Life Sciences is a business unit of Roche Applied Science, a division of Roche Diagnostics. For additional information, please visit www.454.com.