CBSE researchers release complete human genome reference sequence

Monday, April 14, 2003

As leaders of the Human Genome Project announced the project's successful completion at a press conference today in Bethesda, Md., UCSC bioinformatics researchers made the completed reference sequence of the human genome publicly available on the web-based UCSC Genome Browser.

This was also the first site to make the initial working draft of the human genome publicly available in June 2000.

The UCSC Genome Browser provides a web-based "microscope" for exploring the human genome sequence and is used daily by thousands of biomedical researchers throughout the world, said David Haussler, a Howard Hughes Medical Institute investigator and holder of the UC Presidential Chair in Computer Science.

"We have now built the browser on top of the finished genome sequence. That sequence will serve as a new foundation for medicine and human biology, and our browser will form the most popular portal to explore our shared genetic heritage," said Haussler, who directs UCSC's Center for Biomolecular Science and Engineering (CBSE).

The center's Genome Bioinformatics Group worked long hours to get the browser ready for today's announcement of the finished sequence. HHMI postdoctoral researcher Terrence Furey led an effort to ensure that the locations of as many known genes as possible were identified in the genome sequence.

CBSE research scientist James Kent, who earlier assembled the first working draft of the human genome, created the UCSC Genome Browser. The browser displays the genome in alignment with dozens of annotation tracks contributed by researchers at UCSC and collaborators worldwide.

"We have 51 annotation tracks aligned with the genome sequence, so the browser is very rich in information," said Fan Hsu, director of proteomics at CBSE.

The browser is now maintained by a team of engineers led by Kent. It is linked to key additional resources at the European Bioinformatics Institute and the National Center for Biotechnology Information.

In addition to Haussler, Kent, Furey, and Hsu, many other members of the UCSC Genome Bioinformatics Group worked long hours to ensure the success of the UCSC Genome Browser and human genome data releases. They include Matt Schwartz, Angie Hinrichs, Heather Trumbower, Donna Karolchik, Chuck Sugnet, Mark Diekhans, Ryan Weber, Robert Baertsch, Yontao Lu, Krishna Roskin, and several other graduate students in the Haussler lab.

As the focus of the human genome research community shifts from sequencing to sequence analysis, the UCSC Genome Browser is well positioned to fill an essential role in uncovering the causes, treatments, and prevention of disease and in exploring our shared genetic heritage, Haussler said.

"The Human Genome Sequencing Consortium has given us an extraordinary gift. The finished human genome sequence is like a finely polished mirror, reflecting ourselves at the molecular level with unprecedented scope and accuracy," he said.

"I am extremely proud that the UCSC Genome Bioinformatics Group has been able to play a role in this great achievement."

The international effort to sequence the 3 billion DNA letters in the human genome is considered by many to be one of the most ambitious scientific undertakings of all time, even compared to splitting the atom or going to the moon.

"The Human Genome Project has been an amazing adventure into ourselves, to understand our own DNA instruction book, the shared inheritance of all humankind," said Francis Collins, director of the National Human Genome Research Institute (NHGRI) and leader of the Human Genome Project since 1993.

"All of the project's goals have been completed successfully ' well in advance of the original deadline and for a cost substantially less than the original estimates," Collins said.

The flagship effort of the Human Genome Project has been producing the reference sequence of the human genome. The international consortium announced the first draft of the human sequence in June 2000. Since then, researchers have worked tirelessly to convert the "draft" sequence into a "finished" sequence.

Finished sequence is a technical term meaning that the sequence is highly accurate (with fewer than one error per 10,000 letters) and highly contiguous (with the only remaining gaps corresponding to regions whose sequence cannot be reliably resolved with current technology). That standard was first achieved for a human chromosome when a team of British, Japanese, and U.S. researchers produced a finished sequence for human chromosome 22 in 1999.

The finished sequence produced by the Human Genome Project covers about 99 percent of the human genome's gene-containing regions, and it has been sequenced to an accuracy of 99.99 percent.

In addition, to help researchers better understand the meaning of the human genetic instruction book, the project took on a wide range of other goals, from sequencing the genomes of model organisms to developing new technologies to study whole genomes. As of April 14, 2003, all of the Human Genome Project's ambitious goals have been met or surpassed.

"Never would I have dreamed in 1953 that my scientific life would encompass the path from DNA's double helix to the 3 billion steps of the human genome. But when the opportunity arose to sequence the human genome, I knew it was something that could be done--and that must be done," said Nobel Laureate James Watson, president of Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y. "The completion of the Human Genome Project is a truly momentous occasion for every human being around the globe."

The International Human Genome Sequencing Consortium included hundreds of scientists at 20 sequencing centers in China, France, Germany, Great Britain, Japan and the United States. The five institutions that generated the most sequence were: Baylor College of Medicine, Houston; Washington University School of Medicine, St. Louis; Whitehead Institute/MIT Center for Genome Research, Cambridge, Mass.; the Department of Energy's Joint Genome Institute, Walnut Creek, Calif.; and The Wellcome Trust Sanger Institute near Cambridge, England.