![]() This issue... Human Genome Sequencing |
Human Genome Sequencing: Nearing the End of the Beginningby Sallie J. Ortiz
|
![]() |
Craig Venter, Celera Genomics; Ari Patrinos, DOE's Human Genome Program and Office of Biological and Environmental Research; and Francis Collins, NIH's National Human Genome Research Institute. |
This achievement provides scientists worldwide with a virtual road map to an estimated 95% of all genes. The HGP has made a commitment to filling the remaining gaps and resolving all ambiguities in the sequence by 2003. In spite of the few gaps, scientists are already getting a good sense of what the genome landscape looks like and the surprising stories it has to tell. The following are highlights of HGP's findings published in Nature:
The sequence information from the consortium has been immediately and freely released to the world, with no restrictions on its use or redistribution. The information is scanned daily by scientists in academia and industry, as well as by commercial database companies, providing key information services to biotechnologists. Already, many tens of thousands of genes have been identified from the genome sequence, including more than 30 that play a direct role in human disease.
Speaking of the value of genome data and technologies, Patrinos said, "We are eager to offer a future to our children and grandchildren in which cancer will be only a constellation in the sky."
Francis Collins, head of the NIH genome program said, "Researchers in a few years will have trouble imagining how we studied human biology without genome sequence in front of us."
More than $3 billion has been spent worldwide on the private side Human Genome Project since its formal inception in 1990. Although 16 institutions participated in the HGP, most sequencing takes place at 5 locations. These are the DOE Joint Genome Institute, Washington University (St. Louis), Sanger Centre (U.K.), Baylor College of Medicine, and Whitehead Institute. Bioinformatics teams at the Ensembl database project and the University of California, Santa Cruz, generated an ordered view of the 400,000 sequenced DNA fragments in the working draft.
In July 2000, the Wellcome Trust (U.K.) announced a 5-year investment in Ensembl of more than $14 million (£8.8 million) for automatic annotation of human genome data, including identification of genes and other biologically important sequence features.
The HGP's early phase was characterized by efforts to generate the biological, instrumentational, and computational resources necessary for efficient production-scale DNA sequencing. Pilot studies on large-scale sequencing began in 1996, and successes led to a ramp up in 1998.
In 1999, international HGP leaders set the accelerated goal of completing a rough draft of all 24 human chromosomes a year ahead of schedule. Resources pioneered in DOE-sponsored HGP projects (e.g., a new generation of automated capillary DNA sequencing machines and by DNA fragments called BACs) have facilitated this increased pace. Researchers in both the public and private sectors use BACs to speed their sequencing procedures.
The extraordinary achievements of the HGP stand as a testimony to the successful collaborations among scientists intent on overcoming massive technological challenges to move toward the common goal of understanding life at its most basic level. The DNA sequences give scientists the foundations to begin this work.
The status of human genome research today is well represented by the words of Winston Churchill in 1942, who said, after 3 years of war, "Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning."
The HGP plans to sequence the genomes of many other species, because comparing genomes across species will provide researchers key tools for understanding the essential elements that evolution has designated as important to survival. This information will in turn translate into practical knowledge toward developing better therapies in the future.
Comparative genomics will offer scientists insights into important regions in the sequence that perform regulatory functions. Also among the future plans for HGP scientists is the sequencing of other large genomes, such as primates. Scientists also plan to complete the catalogue of human variations in the population and identify the genes that predispose individuals to risk for common diseases.
The sequence will serve as a foundation for a broad range of functional genomic tools to help biologists to probe the function of the genes in a more systematic manner. Development of such post-genomic tools will be one of the major thrusts for biologists in the next decade.
The Department of Energy is poised to move forward in addressing some of these post-sequencing research challenges through a proposed new program called Genomes to Life.
Goals of the Genomes to Life program are to
(1) identify life's molecular machines, the multiprotein complexes that carry out the functions of living systems;
(2) characterize the gene-regulatory networks and processes that
control life's molecular machines;
(3) characterize the functional repertoire of complex microbial communities in their natural environments; and
(4) develop computers and other computational capabilities needed to create models that describe the complexity of biological systems to enable prediction of their behavior and productive use of their functions.
There will be a pressing need for improved methods to analyze the abundance of information being generated. And genetics will become an increasingly important part of the medical mainstream. The pressure will grow to encourage educated use of genetic information and to set thoughtful limits on its use.
Related Web Links:
"On
the Shoulders of Giants: Private Sector Leverages HGP Successes", Human Genome News
Human
Genome Project and the Private Sector: A Working Partnership
"Sharing the Glory, Not the Credit," by Eliot Marshall, Science, Volume 291, Number 5507, 16 Feb 2001, pp. 1189-1193.
Webcast of the "First Analysis of Complete Human Genome Press Conference," February 12, 2001. (Click on Past Events, and then Conferences.)
Human Genome Project: The Science, History, and Societal Issues
Human
Genome Project Information
History
Progress
Goals
Frequently
Asked Questions about the Project
Anticipated
Benefits of HGP Research
Ethical,
Legal, and Social Issues
HGP Data Sites
DOE
Joint Genome Institute
The ENSEMBL Project
European
Bioinformatics Institute
National
Center for Biotechnology Information
University
of California, Santa Cruz
Baylor
College of Medicine
Computational
Biosciences, ORNL See also alternate
site.
DNA
Data Bank of Japan
Genome
Database
GenBank
Sanger
Centre
Stanford
Human Genome Center
Washington
University, St. Louis
Whitehead
Institute
Medical Applications of Genome Research
Basic
Information
Gene
Testing
Gene
Therapy
Pharmacogenomics
Genetic
Counseling
Disease
Research
Publications and Other Resources
Genetics
101an overview
Glossary
of Genetic Terms
Image
Gallery
Human
Genome News
Webcasts
DOE Primer
on Molecular Genetics
To
Know Ourselves
Research
in Progress (More technical information about the HGP)
Fact
Sheet about DOE's involvement in the Human Genome Project