Genome Project 
U.S. HGP on Fast Track 
DOE Joint Genome Institute Exceeds Goal 
New 5-Year Goals 
Faster Sequencing with BACs 
Mapping with STCs and STSs 
Availability of BAC Clones and STC Data 
BAC Related Websites 
BAC Resource Success Story 
Scientists Hunt SNPs for Variation, Disease 
Who's Sequencing the Human Genome? 
Genomics Progress in Science 
EMSL Promotes Remote Access to Instrumentation 
Second Private-Sector Sequencing Project 
GeneMap'98 

In the News 
Team Delivers C. elegans Sequence 
Why Sequence Entire Genomes? Worm's Eye View 
Embnet.news on Web 
European Biotech Program 
DOE BER Research Update 
Hollaender Fellows Named 
SBIR 1998 Human Genome Awards Announced 
Mouse Resources 
Mouse Consortium for Functional Genomics 
Chlamydia Genome Analysis 
HUGO Merges Offices, Web Sites 

Microbial Genomics 
Superbug Deinococcus radiodurans 
Unfinished Microbial Genomes Searchable 
TIGR Releases Chlorobium tepidum Sequence 
DOE MGP Abstracts Online 
Microbial TV Series 
 
Ethical, Legal, and Social Issues and Educational Resources 
Cambridge ELSI Symposium 
Eric Lander, Genetics in the 21st Century 
Mark Rothstein, Genetic Privacy 
James Wilson, Gene Therapy Present & Future 
LeRoy Walters, Ethical Issues in Gene Therapy 
DNA Files on NPR, Internet 
Innovative Biotechnology Curriculum 
Short Course for Biology Teachers 
Microbial TV Series 

Proteomics 
Looking at Proteins to Understand Expression 
2-DGE:  Protein Visualization, Modification 
Tool for Protein Analysis 
TREMBL Release 6 
R&D 100 Award Goes to LANL's SOLVE 
NIH Awards Proteomics Grant to Axys 
E. coli Proteome Database 

Genetics in Medicine 
National Organization for Rare Disorders 
Translation of Genetics to Medicine: New Website 
Cancer Genetics Web Site 
HuGem Website Offers Education in New Genetics 
Calculation of Genetic Risks 2nd Edition 
New Genetics Manual Offered 
Mutation Research Genomics Online 
 
Informatics 
GDB Database Operations Restored 
In Silico Biology: Bioinformatics Journal 
Computational Methods Book Available 
Bioinformatics Guide
BioToolKit
Gene-Finding Programs at Sanger
New Sequin Version
Tandem Repeat Tool
Sequence Viewer
SmithKline Licenses Gene Logic Software 
Influenza Database at LANL 
TRANSFAC Database 
p53 Mutation Database 
TBASE at Jackson Laboratory 
Intein Database on Web 
System Identifies Polymorphisms 

Web, Other Resources, Publications 
1999 Oakland Workshop Website 
Launchpad to Human Chromosomes 
Nature Genetics Supplement 

Funding 
DOE Office of Science Grants and Contracts 
NHGRI National Service Award Fellowships 
NCI Technologies for Molecular Analysis 
NIH: Netork for Large-Scale Mouse Sequencing 
NHGRI: Genomic Technology Development 
US Genome Research Funding 

Meeting Calendars & Acronyms 
Genome and Biotechnology Meetings 
Training Courses and Workshops 
Acronyms 

HGN archives and subscriptions 
HGP Information home

U.S. HGP on Fast Track for Early Completion

In September 1998, advisory committees at DOE and NIH approved new 5-year goals aimed at completing the Human Genome Project (HGP) 2 years earlier than originally planned in 1990. The target date of 2003 also will mark the 50th anniversary of Watson and Crick's description of DNA's fundamental structure.

The new plan was published in the October 23, 1998, issue of Science, which also cited the contributions of international partners. These partners include the Sanger Centre in the United Kingdom and research centers in Germany, Japan, and France.

The U.S. HGP began officially in 1990 as a $3-billion, 15-year program to find the estimated 80,000 human genes and determine the sequence of the 3 billion DNA building blocks that underlie all of human biology and its diversity. The early phase of the HGP was characterized by efforts to create the biological, instrumentation, and computing resources necessary for efficient production-scale DNA sequencing. The first 5-year plan was revised in 1993 due to remarkable technological progress, and the second plan projected goals through FY 1998. The latest plan was developed during a series of individual and joint DOE and NIH workshops held over the past 2 years (see box, p. 3).

Observers have predicted that the 21th century will be the "biology century." The analytical power arising from the reference DNA sequences of several entire genomes and other genomic resources is anticipated to help jump start the new millennium.

Human DNA Sequencing
The HGP's continued emphasis is on obtaining a complete and highly accurate reference sequence (1 error in 10,000 bases) that is largely continuous across each human chromosome. Scientists believe that knowing this sequence is critically important for understanding human biology and for applications to other fields.

The plan calls for generating a "working draft" of the human genome DNA sequence by 2001. The working draft will comprise shotgun sequence data from mapped clones, with gaps and ambiguities unresolved. If these data sets can be merged with those from the private sector, they may increase the depth of the mapped draft, which scientists expect will contain about half the genes. Draft sequence will provide a foundation for obtaining the high-quality finished sequence and also will be a valuable tool for researchers hunting disease genes.

According to Ari Patrinos, DOE Associate Director for Biological and Environmental Research, "Although we have as our primary goal the finished Book of Life' by the end of 2003, we also want the working draft to be as useful as possible."

NIH and DOE sequencing centers expect their facilities to generate about 60% to 70% of the human DNA sequence, which will be made available broadly and rapidly via the Web to stimulate further research.

Sequencing Technology
Although current sequencing capacity is far greater than at the inception of the HGP, achieving the new sequencing goals will require a two- to threefold improvement. Further incremental advances in sequencing technologies, efficiency, and cost will be needed. For future sequencing applications, planners emphasize the importance of supporting novel technologies that may be 5 to 10 years in development.

Sequence Variation
A new goal focuses on identifying individual variations in the human genome. Although more than 99% of human DNA sequences are the same across the population, variations in DNA sequence can have a major impact on how humans respond to disease; environmental insults such as bacteria, viruses, toxins, and chemicals; and drugs and other therapies.

Methods are being developed to detect different types of variation, particularly the most common type called single-nucleotide polymorphisms (SNPs), which occur about once every 100 to 300 bases. Scientists believe SNP maps will help them identify the multiple genes associated with such complex diseases as cancer, diabetes, vascular disease, and some forms of mental illness. These associations are difficult to establish with conventional gene-hunting methods because a single altered gene may make only a small contribution to disease risk.

Functional Genomics
Efficient interpretation of the functions of human genes and other DNA sequences requires that resources and strategies be developed to enable large-scale investigations across whole genomes. A technically challenging first priority is to generate complete sets of full-length cDNA clones and sequences for human and model-organism genes. Other functional-genomics goals include studies into gene expression and control, creation of mutations that cause loss or alteration of function in nonhuman organisms, and development of experimental and computational methods for protein analyses.

Comparative Genomics
The functions of human genes and other DNA regions often are revealed by studying their parallels in nonhumans. To enable such comparisons, HGP researchers have obtained complete genomic sequences for the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae, and the roundworm Caenorhabditis elegans. Sequencing continues on Drosophila melanogaster and the laboratory mouse. The availability of complete genome sequences generated both inside and outside the HGP is driving a major breakthrough in fundamental biology as scientists compare entire genomes to gain new insights into evolutionary, biochemical, genetic, metabolic, and physiological pathways. HGP planners stress the need for a sustainable sequencing capacity to facilitate future comparisons.

Ethical, Legal, and Social Implications (ELSI)
Rapid advances in the science of genetics and its applications present new and complex ethical and policy issues for individuals and society. ELSI programs that identify and address these implications have been an integral part of the U.S. HGP since its inception. These programs have resulted in a body of work that promotes education and helps guide the conduct of genetic research and the development of related medical and public policies.

A continuing challenge is to safeguard the privacy of individuals and groups who contribute DNA samples for large-scale sequence-variation studies. Other concerns are to anticipate how the resulting data may affect concepts of race and ethnicity; identify potential uses (or misuses) of genetic data in workplaces, schools, and courts; identify commercial uses; and foresee impacts of genetic advances on the concepts of humanity and personal responsibility.

Bioinformatics and Computational Biology
Continued investment in current and new databases and analytical tools is critical to the success of the HGP and to the future usefulness of the data it produces. Databases must adapt to the evolving needs of the scientific community and must allow queries to be answered easily. Planners suggest developing a human genome database, analogous to model organism databases, that will link to phenotypic information. Also needed are databases and analytical tools for studying the expanding body of gene-expression and functional data, for modeling complex biological networks and interactions, and for collecting and analyzing sequence-variation data.

Training
Planners note that future genomic scientists will require training in interdisciplinary areas that include biology, computer science, engineering, mathematics, physics, and chemistry. Additionally, scientists with management skills will be needed for leading large data-production efforts.

The HGP already has revolutionized biology by providing tools and resources for basic research and has catalyzed the growth of the life sciences industry. Current and potential applications of genome research address national needs in molecular medicine, waste control and environmental cleanup, agriculture and animal husbandry, biotechnology, energy sources, and risk assessment.

Note: For more on the Five Year Research Goals, see the website.
For more information about project history, see the timeline.

The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v10n1-2)