Mass Analysis of DNA from Whole Populations

20-Apr-2005 1:00 AM EDT

Wellcome Trust

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Newswise — One of the world's leading scientists, Nobel Prize winner, Dr Sydney Brenner, has devised a new method for obtaining sequence information from thousands of genomes simultaneously. Current technologies can only analyse one genome at a time.

This method, to be developed by a new company called Population Genetics Technologies, is expected to reduce significantly the cost of studying large populations of genomes. Such studies are important to the discovery of genetic variations that affect common diseases and to the development of safer, more effective drugs.

The Wellcome Trust, one of the world's leading biomedical research charities, has granted the company a £1.1m Programme Related Investment to enable it to begin development of the technology pending receipt of additional Venture Capital investments. The Intellectual Property and related patent applications underlying the technology were licensed from Compass Genetics LLC, a partnership formed several years ago by Drs Sydney Brenner, Sam Eletr and Philip Goelet.

"In order for disease research to provide more immediate benefits for society, we do not have to know everything about every gene," said Dr. Brenner, who was awarded the Nobel Prize in Physiology or Medicine in 2002*. "What is most important is to discover the variants in genes that contribute to human disease.

"This new technology will enable users to discover extremely quickly much information about such gene variants from studies of whole populations.

"It can be used also for a broad range of complex biological problems requiring many parallel analyses. Examples are elucidating genetic changes in expressed genes in many samples of cancer, or understanding the different responses that people have to drug treatment, so as to better adapt medications to the needs of individual patients.

"For example, the technology might enable the discovery of mutations, rare in a clinical trial population, but responsible for serious deleterious side effects that are discovered only when the drug is very broadly prescribed. Patients that are potentially subject to such side effects could be screened if these mutations are determined."

Dr Sam Eletr, co-founder of the company that developed the first and leading DNA-sequencing machines, said : "Advances in technologies designed to obtain DNA sequence information are moving at a significant pace.

"However our new method, if successful, will be a huge leap forward as it is expected to provide a significant cost advantage over other techniques which analyse one genome at a time, no matter how efficiently.

"This is because our method will allow the mixing of thousands of samples in one test tube and the simultaneous interrogation of all of them in one experiment, instead of in as many experiments as there are genomes in a population.

"Although pooling techniques that allow simultaneous analysis of multiple genomes have been used, these only provide population-wide characteristics, such as the frequency of gene variation, and not information specific to individual genomes.

"We expect our technology to allow handling much larger numbers of genomes than pooling does and to have the further advantage of protecting the identities of individuals involved in any population study by allocating them a code that may be kept confidential. We expect it also be applicable to any collection of DNA molecules and genomes, whether from plants, animals, micro-organisms or humans."

Dr Ted Bianco, Director of the Wellcome Trust's Technology Transfer Division, which made the award, said: "This project, which uses information gained from the Human Genome Project, aims to take this knowledge to another level.

"The scale of its parallel, simultaneous analyses could prove invaluable to programmes such as the UK Biobank Project, which will make DNA samples from 500,000 middle-aged people throughout the UK available for medical research."

Population Genetics Technologies will be located in Cambridge, UK. Its Board of Directors will include Drs Brenner and Eletr and will be chaired by Dr Mark Treherne. Dr Eletr will be acting Chief Executive Officer until the role is permanently filled.

* The 2002 Nobel Prize in Physiology or Medicine was shared between :Dr Sydney Brenner, the Molecular Sciences Institute, Berkeley, CA, USA.H. Robert Horvitz, Massachusetts Institute of Technology, Cambridge, USA.John E. Sulston, Wellcome Trust Sanger Institute, Cambridge, UK.

It was awarded to the three "for their discoveries concerning 'genetic regulation of organ development and programmed cell death'"

Notes :

The Wellcome Trust is an independent research-funding charity established in 1936 under the will of tropical medicine pioneer Sir Henry Wellcome. The Trust's mission is to promote research with the aim of improving human and animal health and it currently spends more than £400m p.a. The Technology Transfer Division manages the charity's intellectual property portfolio and related matters and provides translation funding for early-stage healthcare technology development. Over 70 research and license agreements have been transacted and the division has an interest in around 20 life science Small, Medium Enterprises located in the UK or US

Sydney Brenner was born in South Africa in 1927 and educated at the University of Witwatersrand, Johannesburg (Medicine and Science). At Oxford University he received a degree of D.Phil., in 1952 working in the Physical Chemistry Laboratory. After a brief return to South Africa he joined the Medical Research Council Unit in the Cavendish Laboratory in Cambridge in 1956. He worked there and for its successor, the MRC Laboratory of Molecular Biology in Cambridge where he was the Director from 1979 to 1987. In 1987 he became Director of the MRC Unit of Molecular Genetics retiring in 1992 from the MRC. He is now Distinguished Professor at The Salk Institute, La Jolla, California.

His early research was in molecular genetics, working with bacteriophages and bacteria; he discovered messenger RNA (with Jacob and Meselson) and, with Francis Crick, showed that the code was composed of triplets.

In the sixties, he changed directions and initiated his research on C. elegans establishing it as a powerful experimental system for the analysis of complex biological processes. As a geneticist, he saw that the techniques of cloning and sequencing would open up new ways of approaching genetics and he turned to studying vertebrate genomics and has established the pufferfish genome as a powerful tool in genome analysis.

Sam Eletr, PhD, currently serves as a Director of Third Wave Technologies, a NASDAQ-listed, DNA-based, diagnostic products company, of Faust Pharmaceuticals, a biopharmaceutical company based in Strasbourg, France and of SpinX Technologies, a micro-fluids company based in Geneva, Switzerland. Dr. Eletr also served as a Director of Solexa, Ltd, a developer of DNA sequencing technology based in Cambridge, England, from 2002 until July 2004, and as a Director of i-STAT, a point-of-care diagnostics company, from 2001 until its acquisition by Abbott Laboratories in December 2003.

From 1992 to 1999, Dr. Eletr served as Chairman of the Board of Lynx Therapeutics, a NASDAQ-listed, DNA-sequencing company. In 1980, he co-founded a company that became Applied Biosystems, Inc. (now the Applied Biosystems Group of Applera Corporation), the leading supplier of DNA sequencing and other Biotechnology instruments and reagents, where he served as Chairman and CEO from its founding until 1987. Prior to this, he was Manager of an Analytical and Medical Instruments Group at the Hewlett-Packard corporate research laboratories in Palo Alto. Dr. Eletr obtained an MA in Physics and a PhD in Biophysical Chemistry from the University of California at Berkeley. Prior to his MA, he studied Electrical Engineering at the Polytechnic Institute in Grenoble, France.

Philip Goelet is a director of Red Abbey Venture Partners, LLC, a life sciences private equity partnership, formed with Frank Bonsal and Matt Zuga. He currently manages Acidophil, an intellectual property development company founded with Sydney Brenner and is the acting CEO of its first spin-out, Dihedron Corporation, a drug discovery company focused on cancer. Between 1995 and 2001, Philip served as an officer and director of the Rhode Island Corporation and its successor, NORIC, which was acquired by Pogo Producing Company 2001. He participated in the formation of RiboTargets, Plc., UK, and served on its board from 1997 to 2000. In 1990 he founded Molecular Tool, Inc., where he co-invented SNP ("single nucleotide polymorphism" ) analysis technology. As CEO and Chairman, he completed Molecular Tool's merger with GeneScreen, and as a Director of GeneScreen he participated in its acquisition in 1999 by Orchid Biosciences, Inc., serving on its scientific Advisory Board. Philip received his B.A. from Oxford University and his M.Phil. and Ph.D. in Biochemistry from Cambridge University, UK.

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