DOE Joint Human Genome Effort Exceeds Sequencing Goal

October 23, 1998

BERKELEY, CA -- The U.S. Department of Energy today (Friday, Oct. 23) announced that its Joint Genome Institute (JGI), an integrated three-laboratory effort to help decipher the human genetic code, surpassed its ambitious goal of sequencing 20 million base pairs for fiscal year 1998.

"This achievement marks an unprecedented ten-fold increase in production output over the previous year," said Martha Krebs, the DOE's Director of the Office of Energy Research. "With this milestone, the JGI rises to the third position worldwide in terms of its total contribution of human DNA sequence to public databases, and signals great promise for completion of the entire project in five years."

The JGI, established in 1996, is a consortium of scientists, engineers and support staff from the Lawrence Berkeley, Lawrence Livermore, and Los Alamos National Laboratories. The JGI has assumed a key role in the international effort to determine all 3 billion base pairs ("letters") that comprise the human genome. This worldwide project, the largest biological undertaking in history, promises untold opportunities to understand the basic molecular underpinnings of life and to improve human health.

"Two years ago today, the DOE Human Genome Program took a bold step forward in forming the JGI, and in so doing took advantage of significant economies of scale," Krebs said. "By combining forces of our three genome centers, DOE has clearly established a solid position among the leaders in this exciting pursuit of the first volume in the human book of life."

"The JGI is well on its way to making an important contribution to the quest to discover all human genes and elucidate their functions," said Dr. Elbert Branscomb, Director of the Joint Genome Institute. "I expect that once we are established in our new facility, we will be generating high-quality DNA sequence information at greatly accelerated rates."

During its first full year of operation, the JGI successfully sequenced over 20 million base pairs. Thanks to improved technologies, some developed by JGI researchers, and streamlining techniques, the JGI has been able to reach rates of over 2.5 million base pairs per month. According to Branscomb, the JGI's sequencing goal for 1999 is 70 million high-quality bases -- 30 million finished bases and 40 million "draft" bases.

"This represents only the first step in our aggressive plan for production ramp-up. We are seeking to break the 100-million-base-pair barrier in the year 2000," he said. Thus far, the international human genome sequencing effort has cracked only about 7 percent of the genome's three billion letters, or 195 million bases.

To explore the genetic landscape, researchers construct "maps" by probing for particular biological landmarks along the topography of the human chromosomes. These low-resolution maps capture features along vast stretches of DNA, from thousands to millions of individual units. To reveal the details along the way, the methodical process of sequencing is employed, which photochemically reads the identity and exact order, or sequence, of the four letters that make up the alphabet of DNA.

Of the 23 pairs of human chromosomes, the JGI's sequencing enterprise targets chromosomes 5, 16, and 19, regions of the human genetic library that have already yielded genes involved in diabetes, atherosclerosis, asthma, schizophrenia, and Batten disease (a fatal, inherited disease of the nervous system that begins in childhood).

An accelerated 5-year plan for the U.S. Human Genome Program (the combined DOE and National Institutes of Health efforts) was published today in the journal Science. The new plan calls for the completion of the first high-quality set of human genome sequences by 2003, two years ahead of the original schedule.

Branscomb anticipates that the Joint Genome Institute will begin moving into its new Walnut Creek (CA) operations center, the Production Sequencing Facility (PSF), in November. The PSF will provide 56,600 square feet of laboratory and office space, accommodating at its capacity 200 researchers working in three shifts around the clock. The genomic technologies being developed by the JGI and other efforts around the world, he said, will provide the basic information about human genes needed to address many issues related to disease diagnosis and therapy.

Defective genes directly account for more than 4,000 hereditary human diseases -- including such maladies as Huntington disease and cystic fibrosis. In some such cases, a single misplaced letter among the three-billion-letter code can lead to a disease state.

The benefits of the genome project are already coming to light. A new era of molecular medicine is envisioned that is characterized not by treating symptoms, but rather by looking to the deepest causes of disease. Rapid and more accurate diagnostic tests will make possible earlier treatments. Insights into genetic susceptibilities to disease and to environmental damage, coupled with highly targeted pharmaceuticals, may soon help to attack diseases at their molecular foundations.

The DOE, with a long-abiding mission to understand and characterize the potential health risks posed by energy use and production, has established an unparalleled scientific and engineering infrastructure in its national laboratories and a track record of success in conducting large-scale multidisciplinary projects. In 1986, the DOE was the first federal agency to launch a major initiative to completely decipher the entire human genetic code. Building on the JGI's accomplishment this year, the DOE, according to Krebs, will invest approximately $250 million in the Joint Genome Institute over the next five years.

The full text of the genome program's five-year plan can be found at on the World Wide Web.

DOE/Lawrence Berkeley National Laboratory

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