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Aaron Hall Profile and Articles

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151). Large-Insert Cloning Vectors Aid Function Studies
Collections of human DNA fragments are maintained for research purposes as clones in bacterial host cells. However, for unknown reasons, some regions of the human genome appear to be unclonable or unstable in bacteria. The team led by Jean-Michel Vos [University of North Carolina at Chapel Hill (UNCCH)] has developed a system using episomes (extrachromosomal, autonomously replicating DNA) that maintains large DNA fragments in human cells.

152). Chromosome X Map Completed
On March 14, researchers at Washington University School of Medicine in St.Louis announced the completion of a high-resolution map of chromosome X. This chromosome, which determines gender, is associated with many inherited disorders. Researchers also located hot spots for genes and detected a large region where the DNA remains intact as it passes from one generation to another.

153). Packaging the Genome
Community Resources for Mapping, Sequencing, Finding Genes

Collections of cloned DNA pieces (libraries) provide the essential starting material for genome researchers. Workshop speakers discussed improvements to the depth and quality of a virtual alphabet of clone libraries - BACs, PACs, cDNAs, HAECs, and TAR-YACs - and on their usefulness for mapping, sequencing, and functional analysis.

154). DiGeorge Syndrome Region Cloned
Researchers led by Beverly Emanuel and Marcia Budarf at Children's Hospital of Philadelphia have cloned a region of the chromosome 22 long arm containing a chromosomal breakpoint involved in DiGeorge syndrome (DGS) and have identified candidate genes spanning the breakpoint.

Named for endocrinologist Angelo DiGeorge, who first described the syndrome in 1965, the 22q11 microdeletion associated with DGS is believed to occur about once in 4000 to 5000 births.

155). Chromosome 9 Workshop Produces New Maps
The Fourth International Workshop on Chromosome 9, held April 23-25 in Williamsburg, Virginia, was organized by Margaret Pericak-Vance (Duke University) and attended by 33 people from 7 countries. Sponsors included the U.K. Medical Research Council, DOE, NIH National Center for Human Genome Research, and the Human Genome Organisation (via a grant from the European Community).

156). CSHL Mapping and Sequencing Meeting Held
The Eighth Annual Genome Mapping and Sequencing Meeting, held May 10-14 at Cold Spring Harbor Laboratory, was attended by more than 450 participants with a strong international representation. Over 300 abstracts covered a broad array of topics related to genome analysis of numerous organisms. The meeting was organized by David Bentley (Sanger Centre, U.

157). Groups Publish Detailed Chromosome 22 Map
Research groups led by Beverly Emanuel at the Children's Hospital of Philadelphia (CHOP), the University of Pennsylvania, and the Fox Chase Cancer Center and by Tom Hudson and Eric Lander at Whitehead Institute-Massachusetts Institute of Technology published a detailed physical map of human chromosome 22 in the January 11 issue of Human Molecular Genetics.

158). SNP Consortium Collaborates with HGP, Publishes First Progress Reports
The Human Genome Project (HGP) and The SNP Consortium (TSC,) announced plans to generate a new set of human DNA sequence data that will contribute 125,000 to 250,000 validated and useful DNA markers known as SNPs. The DNA to be sequenced will come from 24 anonymous, unrelated donors with diverse geographic origins, and all data will be made publicly available.

159). JGI Comes of Age: Goals, Progress, and Challenges Outlined
Scientific Director Branscomb Offers "State of JGI" Message
With its multicultural Hispanic, Anglo, and Indian heritages, Santa Fe seemed an appropriate venue for discussing the challenges of forging a union from various independent cultures. Joint Genome Institute (JGI) Scientific Director Elbert Branscomb acknowledged the formidable challenges in joining DOE's three genome centers.

160). New DOE Awards for Collaboration with JGI
Following two competitions, DOE awarded grants for collaborations with JGI. The awards, announced in February and March, went to investigators at universities, industries, and national laboratories to provide additional technologies, expertise, and resources for human genome research and functional genomics.
* Jack Barber (Immusol Inc.) and Gerald Rubin (University of California, Berkeley): Grants for research on human gene function via use of ribozymes and comparison with Drosophila, respectively.

161). Complete E. coli Genome Sequence in Public Databases
In September 1997, a team of scientists led by Frederick Blattner (University of Wisconsin, Madison) reported completing the sequence of the 4.6-Mb Escherichia coli K-12 genome. The paper published in Science (277, 1453–62) represents an analysis of data collected by more than 259 people over the project's 6-year duration.

Obtaining the complete DNA sequence of the E.

162). New HGP Spinoff Programs to study Genes for Environmental Risk
Although all people are equipped with the same basic set of genes and DNA regulatory regions, close comparisons among individuals reveal their true diversity, with a variation occurring about once every 500 to 1000 bp along the 3-billion-bp human genome. Some of these changes account for such obvious traits as the shape of the nose, height, and hair color, but some gene variations produce no apparent phenotypic differences.

163). Conference on Small Genomes Held at Hilton Head
At the January 1997 Conference on Small Genomes: Sequencing, Functional Characterization, and Comparative Genomics, over 250 participants gathered on Hilton Head Island to discuss recent progress and future directions in this emerging and exciting area of research. As stated by Craig Venter [The Institute for Genomic Research (TIGR)] in the opening session, small-genome research is growing exponentially, and a new era of biological insight is emerging because of it.

164). BAC End-Sequencing Projects Initiated
Assembling ordered, overlapping sets (contigs) of high-quality, - sequence-ready clones has long been considered an essential step toward human genome sequencing. Not only do the clones provide uniform materials for sequencing, but, because they have been mapped to precise genomic locations, the DNA sequence obtained from them can be located on the chromosomes with minimal uncertainty.

165). Mutation Database Initiative
Over the last 5 years, the Human Genome Project has had an enormous impact on the scientific community, which is witnessing an explosive increase in the description of genes and disease-causing mutations. As a result of this overwhelming expansion of data, many problems have arisen in describing and cataloguing sequence alterations and making them accessible to researchers.

166). NCHGR Initiates Sequencing Pilot Projects
The NIH National Center for Human Genome Research (NCHGR) recently announced a pilot study to explore the feasibility of large-scale sequencing of human DNA. This initiative, which is budgeted at $60 million over 3 years, involves six U.S. research centers and is projected to produce the sequence of about 3% of human DNA in the first 2 years.

The pilot study is designed to show whether large-scale sequencing can be done rapidly, accurately, and cost-effectively using current strategies and variations.

167). Sandia, Celera, Compaq Work on Next-Generation Computing
In January, Sandia National Laboratories and Celera Genomics, Inc., signed a 4-year Cooperative Research and Development Agreement to begin work on the next generation of computer software and hardware for computational biology and a full range of applications in the life sciences. Under contract to Sandia, Compaq Computer Corporation will design the new machine, which is expected to achieve 100 trillion operations per second (100 TeraOps).

168). TIGR Gene Index
Researchers now have free Internet access to the Human Gene Index (HGI) database released by The Institute for Genomic Research (TIGR). Designed to integrate research from human genome projects worldwide, the massive HGI holds full-length gene sequences, more than 600,000 ESTs, and 63,000 tentative human consensus sequences. The ultimate goal is to represent a nonredundant view of all human genes with data on their expression patterns, cellular roles, functions, and evolutionary relationships.

169). Capturing the Data and Making It Useful
Redesigning GDB and GSDB

The explosive growth of information and the challenges of acquiring, representing, and providing access to data pose new and monumental tasks for the large public databases. Ken Fasman [Genome Database (GDB)] and Gifford Keen [Genome Sequence Data Base (GSDB)] discussed the restructuring of GDB and GSDB to handle the flood of data and make it useful for downstream biology.

170). The Genome Data Base, Then and Now
When the Genome Data Base began public operation at Johns Hopkins University in 1990, researchers had been mapping the human genome for several decades. In keeping with the Human Genome Project's mission to make mapping data freely accessible to the scientific community, GDB set about curating the existing data and making the information available to those engaged in the mapping effort.

171). DOE and NIH Teams to Unlock Power of Proteins
NIGMS Structural Genome Initiative

Seven new grants, four of them awarded to scientists at DOE sites, are key components in the Structural Genome Initiative started by the NIH National Institute of General Medical Sciences (NIGMS). Over the next decade, the new study will determine the form and function of thousands of proteins.

"These awards demonstrate.

172). Mouse Consortium for Functional Genomics
Six Tennessee research organizations located from Memphis to Knoxville signed a Memorandum of Cooperation on December 4, 1998, to form the Tennessee Mouse Consortium for Functional Genomics. The consortium's purpose is to induce gene mutations in mice as models for human genetic diseases and as subjects for studying gene function. Consortium members are Oak Ridge National Laboratory (ORNL), University of Tennessee (Knoxville and Memphis), Vanderbilt University Medical Center, Meharry Medical College, and St.

173). EcoCyc Database for E. coli
The EcoCyc electronic database is a literature-derived resource that describes the genome and biochemical machinery of Escherichia coli. The database contains up-to-date annotations and the DNA sequences of all genes in E. coli and describes all known pathways of its small-molecule metabolism. Each pathway and its component reactions and enzymes are annotated in rich detail, with extensive references to the biomedical literature.

174). Thermotoga Sequence Presented
In May, researchers led by Karen Nelson (The Institute for Genomic Research) reported obtaining the complete 1.8-Mb genomic sequence of the heat-loving bacterium Thermotoga maritima, first isolated from geothermally heated marine sediment in Vulcano, Italy. Early analysis reveals some unusual features that could affect our understanding of how earth's simplest life forms evolved.

175). Genome of Historic Microbe Sequenced
A team headed by Douglas Smith (Genome Therapeutics, GTC) has finished sequencing the 4.1-Mb genome of Clostridium acetobutylicum and has placed the data in GenBank and on the Web.

C. acetobutylicum, a nonpathogenic microbe that can convert starch into the solvents acetone and butanol, enjoys an unusual place in history. Discovered in 1915 by Chaim Weizmann, the microbe was used by Great Britain during World War I for generating acetone to produce cordite for artillery shells.

176). DOE Refocuses Instrumentation Program
In April the DOE Office of Biological and Environmental Research (OBER) announced its interest in receiving new applications in genome instrumentation research for both substantial evolutionary improvements in current systems and revolutionary technologies for the post-2005 era. To stimulate contributions from investigators not previously involved in DOE's Human Genome Program, OBER invited applications from a broad range of scientists with backgrounds in biology, chemistry, physics, and engineering.

177). What are Genetically Modified (GM) Organisms and Foods?
Although biotechnology and genetic modification commonly are used interchangeably, GM is a special set of technologies that alter the DNA of such living organisms as animals, plants, or bacteria. Biotechnology, a more general term, refers to using natural living organisms or their components.

Combining DNA from different organisms is known as recombinant DNA technology, and the resulting organism is said to be “genetically modified,” “genetically engineered,” or “transgenic.

178). DOE-Funded DNA-Based Technologies Track Identity, Origin of Biological Agents
In cases of bioterrorist attack such as the recent anthrax outbreaks, decision makers and law enforcement officials need to understand the situation quickly. Early detection and identification of the biological organism and its source are crucial for minimizing the potentially catastrophic human and economic costs of such an attack.

Clues may lie hidden in the weapon itself.

179). Spinach Protein Offers New Hope for the Blind
Spinach may make Popeye the Sailor Man strong, but a protein from spinach may someday strengthen the vision of people who can barely see. Researchers at Oak Ridge National Laboratory (ORNL) and the University of Southern California (USC) are investigating whether this chlorophyll-containing protein might be useful in restoring sight by replacing a key light-receiving} part of the human eye that has lost its ability to function.

180). Importance of Intrinsic Disorder for Protein Function
Protein function generally is thought to follow from, indeed to require, a specific three-dimensional (3-D) structure. This view arose 100 years ago in Fischers lock-and-key proposal. About 70 years ago Wu and, independently, Mirsky and Pauling proposed that proteins assume particular 3-D structures as the result of weak interactions and that denaturation results from disruption of these weak forces accompanied by loss of specific 3-D structure.

181). 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.

182). I.M.A.G.E. Consortium Aiding Rapid Development of Human Gene Catalog
In a cDNA library, the numerical representation of particular cDNAs varies over a thousandfold. The predominant members of cDNA libraries from all tissues are the genes for cellular maintenance functions. I.M.A.G.E.'s coordination minimizes the unwanted and expensive repetitive analysis of the already characterized cDNAs.

A single sequencing read of a few hundred cDNA bases usually is sufficient to serve as a distinguishing identifier (EST) of the predecessor mRNA.

183). Justice Faces the Genome: Trials and Tribulations
For most visitors to Cape Cod, parades, picnics, and fireworks are the usual topics of conversation during the Fourth of July week. Among the throngs of vacationers this summer was a group of judges, science advisors, and others bent on more serious discussion during a week-long meeting sponsored by the Ethical, Legal, and Social Issues (ELSI) component of the DOE Human Genome Program.

184). Optical Mapping Offers Fast, Accurate Method for Generating Restriction Maps
Development of cheaper and faster technologies for large-scale genome mapping has been a major priority in the first 5 years of the Human Genome Project. Although many efforts have focused on improving standard gel electrophoresis and hybridization methods,a new approach using optical detection of single DNA molecules shows great promise for rapid construction of ordered genome maps based on restriction endonuclease cutting sites.

185). Plant Genome Significant to Agriculture, Energy, Human Health
For the first time, scientists have sequenced the complete genetic material of a plant, that of the mustard weed Arabidopsis thaliana. The international Arabidopsis Genome Initiative (AGI) consortium published the results and early analyses in the December 14, 2000, issue of Nature, and articles are freely available on the Web through Nature's Genome Gateway.

186). CME Genetics Conference for Physicians
The debut conference in the Continuing Medical Education (CME) series on genetics of the National Center for Genome Resources (NCGR) drew about 50 key educators from the nation's medical schools and societies to Santa Fe in July 1997. Participants at the conference, jointly sponsored by NCGR and the American Medical Association (AMA), explored the potential impact of clinical and ethical genetics issues on the practice of medicine.

187). Teens Collaborate in DNA Sequencing
Unique Program Teaches Via Research Participation

Sequencing the human genome may seem an unlikely activity for teenagers, but Maureen Munn says it's a great way to get them really thinking about genome science and the implications of genetic testing.

"We're making research real for them," says Munn, director of the High School Human Genome Program at the University of Washington in Seattle.

188). Genetics Exhibit Opens in Los Alamos
"Understanding Our Genetic Inheritance" officially opened September 30 at the Bradbury Science Museum in Los Alamos, New Mexico. This exhibit explains the contributions of the Center for Human Genome Studies at Los Alamos National Laboratory (LANL) to the Human Genome Project the international effort to map all the genetic information in human cells.

189). Witnesses Testify About Patenting Genes
On July 13, witnesses presented testimony during a House of Representatives hearing on Gene Patents and Other Genomic Inventions held by the Committee on the Judiciary, Subcommittee on Courts and Intellectual Property.

At the hearing, Harold Varmus (Memorial Sloan-Kettering Cancer Center) stated that some of the issued patents appear to reward the obvious in DNA sequencing and diminish the innovative work required to determine gene function and utility.

190). "Human Gene Therapy: Present and Future"
In his presentation at the 1998 Cambridge meeting, James Wilson characterized gene therapy as a novel approach in its very early stages. Its purpose, he said, is to change the expression of some genes in an attempt to treat, cure, or ultimately prevent disease. Current gene therapy is primarily experiment based, with a few early human clinical trials under way.

191). Should the Public-Minorities in Particular-Be Concerned About the Human Genome Project?
Leading genome scientists and bioethicists, concerned about the societal impacts of genetic discoveries from the Human Genome Project, met in September at Tuskegee University to address some of the project's implications for African Americans. Attendees noted the significance and appropriateness of the location in that Tuskegee is the county seat of Macon County, Alabama, site of the most infamous government medical experiment gone awry.

192). Industry Moves DNA Patenting Forward
Quick public access to sequence data remains a hallmark of the - Human Genome Project for many genome researchers in the United States and worldwide [see HGN 7(5)]. At the same time, private companies are filing applications to patent DNA sequences at unprecedented rates.

These new patent applications are challenging the capacity of the U.S. Patent and Trademark Office (PTO) to review them.

193). Patenting and Database Controversies --- Does the One with the Most Sequence Really Win?
Rebecca Eisenberg (University of Michigan Law School) raised intriguing questions about the proper roles of government and industry in genomic research. One consideration is who stands to benefit (and to lose) rom the private appropriation of genomic information. Controversy, she noted, is particularly acute over the intellectual property rights in large-scale cDNA sequencing data.

194). Genetic Privacy Act Introduced
The Genetic Privacy Act is a proposal for legislation governing collection, analysis, storage, and use of DNA samples and the genetic information obtained from them. This first legislative product of the U.S. Human Genome Project's Ethical, Legal, and Social Issues (ELSI) component was presented to the DOE-NIH Joint ELSI Working Group in December 1994.

195). Genetic Testing, Genetic Counseling Resources
GeneTests and GeneClinics, companion resources on genetic counseling and testing for hereditary disorders, are freely available on the Web. In the past year, several new features and many disease profiles have been added.

GeneTests
http://www.genetests.org: Genetics Laboratory Directory: List of about 500 U.S. and international laboratories that are testing for some 820 diseases; searchable by a variety of parameters, including disease name, gene name, affected organ system, and others.

196). Human Genome Project Directors, Researchers Receive Awards
Ari Patrinos, head of DOE's Human Genome Program, received the 21st Century Pioneer Award in June along with two of his predecessors, Charles DeLisi (Boston University) and David Galas (Keck Graduate Institute). Other recipients were Francis Collins, director of the NIH National Human Genome Research Institute, and representatives from the Wellcome Trust and the Institute of Medical Science at the University of Tokyo.

197). 1999 Hollaender Winners Announced*
DOE has announced the award of nine 1999 Alexander Hollaender Distinguished Postdoctoral Fellowships for up to 2 years of research at DOE laboratories having substantial programs supportive of the Office of Biological and Environmental Research's mission. The mission is to understand health and environmental effects associated with energy technologies and to develop and sustain research programs in life, biomedical, and environmental sciences.

198). DOE Genome Researchers Win R&D 100 Awards
DOE researchers in 12 facilities across the country won 36 of the 100 awards given by R&D magazine for 1996 work. DOE award-winning research ranged from advances in supercomputing to the biological recycling of tires. Announced in July 1997, these awards bring DOE's R&D 100 total to 453, the most of any single organization and twice as many as all other government agencies combined.

199). SBIR 1997 Human Genome Awards Announced
In July 1997 the DOE Office of Biological and Environmental Research announced three Phase I and two Phase II awards in human genome topics of the Small Business Innovation Research (SBIR) program (see box below). The highly competitive SBIR awards are designed to stimulate commercialization of federally funded research and development for the benefit of both private and public sectors.

200). Hollaender Fellows Named
DOE has announced the award of 11 FY 1997 Alexander Hollaender Distinguished Postdoctoral Fellowships for up to 2 years of research at DOE laboratories having substantial programs supportive of the Office of Biological and Environmental Research's mission. The mission is to understand health and environmental effects associated with energy technologies and to develop and sustain research programs in life, biomedical, and environmental sciences.



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