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Pilot Study Explores Feasibility of Sequencing Human DNAApril 1996The National Human Genome Research Institute (NHGRI), a key player in the international Human Genome Project (HGP) and part of the National Institutes of Health (NIH), announced today the launch of an unprecedented pilot study to explore the feasibility of large-scale sequencing of human DNA. This initiative, which is budgeted at over $18 million in the first year and $60 million over three years, marks the transition to the third and most technologically challenging phase of the HGP - determining the sequence of the 3 billion subunits, or bases, of human DNA. This initiative will involve six U.S. research centers and is projected to produce the sequence of about 3 percent of human DNA in the first two years. According to Dr. Francis Collins, NHGRI director, these studies will help to streamline and cut the cost of DNA sequencing. If the pilot study shows such large-scale sequencing can be done rapidly, accurately and cost-effectively, the HGP will be poised to scale up its efforts to sequence the entire human genome on time, by the year 2005, which is the project's dominant goal. "I'm extremely optimistic that in three years we'll be in a position to go after the complete human sequence in earnest," said Dr. Collins. The six groups participating in the pilot projects will strive for an accuracy level approaching one error per 10,000 bases, or 99.99 percent accuracy, in all regions of the genome. But, according to NHGRI's assistant director for program coordination, Dr. Mark Guyer, "The pilot project will help us determine whether it will be necessary to strive for 99.99 percent accuracy when we scale up, and whether it can be done cost effectively with the sequencing strategies emerging during the next three years." Given the value of this information in a host of research settings, especially for finding genes linked to disease, sequence data from the studies will be uploaded rapidly into the public computer databases GenBank and Genome Sequence DataBase, and to World Wide Web pages at the project sites. NHGRI is encouraging the grantees to release preliminary DNA sequence information to the research community within a few days or weeks of its discovery. This is much faster than research information is usually released, but the tremendous value of this data for disease research justifies this aggressive policy. The "finished" sequence, with all data double- and triple-checked, is to be placed in public databases soon after that. NHGRI is discouraging pilot project scientists from seeking patents on the raw genomic sequence. The scientists are free to apply for patents if they have done additional biological experiments that reveal convincing evidence for utility of the sequence - a standard criterion for patenting. Patent protection encourages companies to invest the large sums of money needed to develop diagnostic and therapeutic products. However, according to NHGRI, patent applications on large blocks of primary human genomic DNA sequence could have a chilling effect on the development of future inventions of useful products. This policy responds to recommendations made by several advisory groups that helped formulate the structure and goals of the HGP, and those made at a recent meeting of scientists planning for large-scale human DNA sequencing. The immediate challenge for the pilot study is to refine strategies needed to determine the order of the 3 billion bases in the genome, analyze that information, and present it to the rest of the biomedical research community. The amount of information involved is huge by conventional standards: if you were to print out all the information in the human genome, letter by letter, it would fill a stack of books as tall as a 12-story building. When the HGP was launched in 1990, experts set out a series of goals that were to be met. The first, construction of a human genetic linkage map, was completed in 1994, a year ahead of schedule. The genetic map is used to study how diseases are inherited in families, and the goal was completed when the map contained enough landmarks to be equal to one marker every mile along a road leading from New York to San Francisco. The physical map will probably be complete next year, also a year ahead of schedule. The physical map is used for locating the genes that are involved in disease and normal human development. When it is done, the spacing of markers will be equivalent to having a milepost every tenth of a mile along the road from New York to San Francisco. To prepare for DNA sequencing, NHGRI has been supporting research on developing instruments, computer programs and molecular biology methods. In particular, just within the past year, NHGRI has committed approximately $25 million in two special initiatives to develop specific technologies that will decrease the cost and increase the throughput of large-scale DNA sequencing. Projects to sequence the DNA of a bacterium, yeast, a worm and a fly have also been supported. These projects are an opportunity for scientists to "practice" sequencing on genomes that are much smaller than that of the human, but bigger than anything that had been sequenced before. They also help scientists understand human DNA, because the "model organism" DNA contains information very similar to part of the information in the human genome. The pilot projects begin with lessons learned in model organism and smaller scale, human DNA sequencing, but also emphasize the continued need for innovation and labor-saving strategies. Indeed, the pilot projects will test a number of approaches that could have a profound impact on large-scale sequencing not only for the HGP, but for the rest of science and industry. These innovations include full automation using robotic arms and advanced biochemistry to purify and make ready tens of thousands of DNA samples per day; computer systems to track hundreds of thousands of samples through the laboratory and collect and analyze millions of "letters" of DNA sequence; software to automate decision-making processes; and strategies for converting available DNA maps, which are of high quality but only moderate detail, into a form that will feed identified DNA fragments into the sequencing process. The principal investigators and information on individual projects, including the dollar amounts for the first year of the grants, is provided: Mark D. Adams, Ph.D., The Institute for Genomic Research, Rockville, MD ($3.2 million): Richard A. Gibbs, Ph.D., Baylor College of Medicine, Houston, TX ($1.3 million): Eric S. Lander, Ph.D., Whitehead Institute for Biomedical Research, Cambridge, MA ($4.1 million): Richard M. Myers, Ph.D., Stanford University, Stanford, CA ($2.5 million): Maynard V. Olson, Ph.D., University of Washington, Seattle, WA ($1 million): Robert H. Waterston, M.D., Ph.D., Washington University, St. Louis, MO. ($6.7 million):
Last Reviewed: September 2006 |
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