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Aaron Hall Profile and Articles
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101). Role of Media and Genome Project Addressed
Some 300 scientists, journalists, and teachers attended the December 3, 1994, conference on "Genes that Make News, News that Makes Genes: Reporting on Complex Traits." The meeting, partially funded by DOE, was the fourth in a series of Science and Journalism conferences organized by the Genetic Screening Study Group (Boston) to explore relationships between science and the media.
102). DOE Hits Sequencing Goal
JGI Strategies Pay Off for Chromosomes 5, 16, 19
On April 13, the U.S. Secretary of Energy announced that researchers at the DOE Joint Genome Institute (JGI) had determined the draft sequence for human chromosomes 5, 16, and 19. The three contain more than 300 million bases or about 10% of the total human genome, with an estimated 10,000 to 15,000 genes.
103). SBIR 1998 Human Genome Awards Announced
The DOE Office of Biological and Environmental Research has announced four Phase I and three Phase II awards for 1998 in human genome topics of the Small Business Innovation Research (SBIR) program. The highly competitive SBIR awards are designed to stimulate commercialization of federally funded research and development for the benefit of both the private and public sectors.
104). Anticipated Benefits of Genome Research
Predictions of biology as “the science of the 21st century” have been made by observers as diverse as Microsoft chairman Bill Gates and U.S. President Bill Clinton. Already revolutionizing biology, genome research has spawned a burgeoning biotechnology industry and is providing a vital thrust to the increasing productivity and pervasiveness of the life sciences.
105). Palazzolo Named Genome Center Director
Michael Palazzolo has been appointed Director of the Human Genome Center at Lawrence BerkeleyNational Laboratory (LBNL). In making the announcement, LBNL Director Charles Shank said Palazzolo "has developed and adapted new technologies to directly sequence DNA on a massive scale. His innovations have been key to placing the Berkeley Genome Center at the cutting edge of genomic sciences worldwide.
106). Focus Moves from Transcriptional Mapping to Gene-Function Studies
The Sixth International Workshop on the Identification of Transcribed Sequences was held October 2-5, 1996, in Edinburgh, Scotland. The meeting attracted 46 speakers with 20 posters to discuss topics including the generation of regional and chromosomal transcriptional maps, functional analysis of gene expression, techniques for isolating and analyzing genes, use of model organisms, and informatics.
107). Software Finds Genes Across Species
New software called PROCRUSTES, described in the August 20 issue of the Proceedings of the National Academy of Sciences, can identify with remarkable accuracy human versions of genes found in other life forms. The product of a collaboration between an American and two Russian researchers, PROCRUSTES is considered far more useful than existing techniques if a related pattern is known.
108). Chromosome 19 Map: Status and New Applications
Emilio Garcia summarized the state of the LLNL high-resolution chromosome 19 physical map and discussed its value for gene hunting and detailed analyses of genome organization.
Physical Map
The cosmid-based physical map now consists of 32 islands, 3 in the q arm and 29 in the p arm, with average gap sizes of 90 and 70 kb, respectively. A unique map feature is its metric backbone, in which distance between ordered contigs was estimated using FISH; gap distances are known.
109). LLNL Publishes Chromosome 19 Metric Physical Map
Researchers at the Human Genome Center of Lawrence Livermore National Laboratory have completed an integrated metric physical map of human chromosome 19 that spans over 95% of the euchromatin (about 50 Mb).
Appearing in the December 1995 issue of Nature Genetics (11, 422-27), the map is based on sets of overlapping cosmid clones (contigs); gaps between contigs were filled using various types of larger-insert clones.
110). Using RH Mapping, Rhserver To Incorporate Human ESTs, STSs with Linkage Maps
Meiotic linkage maps consisting of highly polymorphic, PCR-based markers spanning the human genome have had a tremendous impact on the positional cloning of human disease genes in recent years. The availability of cDNA sequences representing the majority of human genes promises to have an equally dramatic impact on human genetic research over the next few years.
111). Human-Mouse Comparisons Identify Candidate Sequences
Less than 5% of the 3.2 billion bases in the human genome sequence is thought to be occupied by genes, regulatory elements controlling gene expression, and other DNA regions that serve important known biological functions. One of the most efficient ways to identify these rare sequence features is to compare human DNA sequence with that of a related but divergent species such as the mouse.
112). International SNP Meetings
Some 100 invited international researchers from industry and academia attended the Second International Meeting on Single Nucleotide Polymorphism (SNP) and Complex Genome Analysis held in Munich, Germany, in September 1999. Below is a summary of meeting highlights with updates from the September 2000 meeting in Taos, New Mexico.
The overall tone of the 1999 meeting showed that SNP research still lacks a solid consensus about how best to proceedand this is at a time when vast sums of money are being spent on public and private SNP programs.
113). Gene-Discovery Resources
Over the years, the team led by Bento Soares (University of Iowa) has optimized methods for producing cDNA libraries, a technically challenging undertaking, and is continuing to produce libraries of the highest quality. Individual clones from these libraries have been arrayed at Livermore and distributed worldwide for characterization by the international I.
114). Early History of Small Genome Sequencing
In 1977, bacteriophage phi-x174 (5386bp) became the first organism to be sequenced completely, by Sanger and colleagues [Nature 246, 687 (1977)]. In 1982, bacteriophage lambda (48,502bp) was completed using a strategy based on sequencing random fragments of DNA, in this case produced by digesting the lambda genome with restriction enzymes, again by Sanger and colleagues [J.
115). Arabidopsis Sequencing Scales Up
Scientists soon will have access to the first complete genetic information of a flowering plant. DOE, the National Science Foundation (NSF), and the Department of Agriculture (USDA) are funding three groups of researchers to begin systematic, large-scale genomic sequencing of Arabidopsis thaliana. It has the smallest genome (about 120 Mb) and the highest gene density known in a flowering plant.
116). Maximizing the Value of Sequence Data
"Obtaining a functional understanding of sequence data is truly a profound challenge," Elbert Branscomb said recently. One method for determining the function of anonymous stretches of sequence data is by computer analysis. Some programs like GRAIL (Gene Recognition and Analysis Internet Link) help detect certain kinds of functional features in sequence data, while others (e.
117). Data Surge Challenges Informatics Developers
The explosive growth of sequence and biological information poses pressing challenges for data acquisition, representation, access, and analysis. Some highlights from informatics sessions at the Santa Fe workshop follow.
bioWidgets: Adaptable, Reusable Modules for Viewing Data
Many software analysis applications commonly are tailored to fit resources available at a particular site.
118). Genome Annotation: Informatics Advances Needed for Age of Functional Genomics
Sharply increasing rates of sequence-data production are placing greater and greater demands on information systems for new ways to view and better understand the meaning of the growing strings of As, Cs, Ts, and Gs piling up in GenBank and community databases. Enriching data with such information as gene features and locations, gene-control regions,.
119). FlyBase Updated
In its most recent update of May 1997, the Drosophila database FlyBase contains information about more than 46,000 alleles of some 14,000 genes. Many gene reports now link to reports about expression patterns and other features for associated proteins and transcripts. FlyBase presents descriptions of over 15,000 chromosomal aberrations as well as molecular maps and information about more than 1000 molecular constructs and 1000 transposons.
120). Second Meeting Held on Interconnection of Molecular Biology Databases
The Second Meeting on Interconnection of Molecular Biology Databases (MIMBD-95) was held at Cambridge University on July 20-22, 1995, in conjunction with ISMB-95. The workshop was organized by Peter Karp of the SRI International Artificial Intelligence Center, Victor M. Markowitz of Lawrence Berkeley National Laboratory, and Tom Flores of the European Bioinformatics Institute.
121). Database Workshops Held
Two workshops have been held entitled Interconnection of Molecular Biology Databases. The first was at Stanford University on August 9-12, 1994, with a 1995 follow-up on July 20-22 in Cambridge, England. Several workshop-related documents are available now. These include the 1994 final report; attendee abstracts and contact information; bibliography on database interoperation; summary of biological databases and WWW pointers; and a list of presentations for the 1995 conference.
122). Interoperable Tools Working Group Meets
An informal off-site informatics meeting was held on November 15, 1994, as an adjunct to the DOE Human Genome Program Contractor-Grantee Workshop in Santa Fe, New Mexico. The discussion at the National Center for Genome Resources involved about 25 NIH and DOE investigators. Its purpose was to develop ideas and a working plan for an interoperable framework of genome-analysis tools.
123). Bio-Science News From the National Laboratories
A new technique for detecting proteins associated with prostate cancer may serve as a sensitive assay for this common killer and have wide applications beyond diagnostics as well. The work was reported in the September 2001 issue of Nature Biotechnology by a team of researchers led by Thomas Thundat (Oak Ridge National Laboratory), Arun Majumdar (University of California, Berkeley), and Richard Cote (University of Southern California).
124). Merck Genomics Institute Established
On April 9, Merck & Co., Inc., announced the establishment of the Merck Genome Research Institute, Inc. (MGRI) to support development of scientific technology for linking human genetic traits and resolving biological function of disease genes. This not-for-profit institute will promote and sponsor projects for broadly applicable assays and methodologies to improve the accuracy and speed with which function can be associated with sequences of genetic information.
125). TIGR Sequencing Anthrax Used in Florida Attack
The National Science Foundation is funding The Institute for Genomic Research (TIGR) to sequence to 8 X coverage the genome of the Bacillus anthracis strain used in last falls attack on a Florida publishing company. TIGR previously sequenced the genome of a more common strain of B. anthracis. Sequence comparisons may help pinpoint the Florida strain’s source and determine whether its genome had been manipulated to increase its virulence.
126). On the Shoulders of Giants: Private Sector Leverages HGP Successes
Data, Technologies Catalyze a New, High-Profile Life Sciences Industry
The deluge of data and related technologies generated by the Human Genome Project (HGP) and other genomic research presents a broad array of commercial opportunities. Seemingly limitless applications cross boundaries from medicine and food to energy and environmental resources, and predictions are that life sciences may become the largest sector in the U.
127). DOE Joint Genome Institute Exceeds DNA Sequencing Goal
The DOE Joint Genome Institute (JGI) surpassed its sequencing goal of 20 Mb of human DNA for FY 1998, marking almost a tenfold increase in production over the previous year.
"With this milestone, JGI rises to 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 [Human Genome] project in 5 years," noted Martha Krebs, Director of the DOE Office of Science.
128). EMSL User Facility Promotes Remote Access to Instrumentation
On October 1, 1998, the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL), DOE's newest National Scientific User Facility, celebrated the first anniversary of its opening in Richland, Washington. The mission of a user facility is to provide unique research resources to scientists from DOE and government laboratories, universities, and industry.
129). Support in the United States
Several U.S. funding agencies provide support for cDNA-related projects. To annotate developing chromosome maps, DOE in 1990 began dedicated support for improved cDNA library production, early EST generation by J. Craig Venter's team at TIGR, physical mapping of cDNAs onto chromosomes, and database support. High-throughput correlations of cDNAs with the new BAC resources are also in progress.
130). Rapid Sequencing of Microbial Genomes Opens Door to Functional Genomics
"Microbial Genome Research and Its Applications" was the topic of the 35th Hanford Symposium on Health and the Environment held October 21-24, 1996, in Richland, Washington.1 According to participants, the genomes of as many as 100 microorganisms are expected to be completely or partially sequenced by the turn of the century.2 The overriding question.
131). Archaic Overachiever Thrives in Hostile Environments
First discovered almost 20 years ago by Carl Woese and Ralph S. Wolfe (both of University of Illinois, Urbana), the Archaea domain (whose name means "ancient" in Greek) is believed to have separated from true bacteria over 3 billion years ago. Archaea once were thought to live only at extreme environmental conditions of temperature and pressure but now are believed to be far more common and to make up a significant part perhaps half of the world's biomass.
132). HuGEM to Educate Health Professionals in Genetics
In a national survey of 329 health professionals who provide services to people with genetic disorders in university-affiliated programs across the country, investigators found that almost 70% reported having no course work in human genetics. The survey, conducted during the Human Genome Education Model (HuGEM) Project, targeted health professionals who furnish preventive, diagnostic, referral, advocacy, therapeutic, educational, or counseling services.
133). Genome FAQs
Relatively Speaking
The many visitors (some 7000 a month) to the Human Genome Project Information Web site ask us interesting questions about genetics and the Human Genome Project. Some we answer directly, and others we refer to leading researchers in relevant fields. From time to time, HGN will print answers to selected frequently asked questions (FAQs).
134). Judging Molecular Biology of Murder, Addictive Disorders, and Dementia
Neurobehavioral Genetics Training Course for Judges
Sixty learners stare at cross-section images of living brains projected on the screen at Airlie Conference Center, an hour out of Washington in Northern Virginias rolling horse country. Drawn to a specialized 3-day training program on neurobehavioral genetics, they strain to find red and white spots indicating mental activity.
135). Fast Forward to 2020: What to Expect in Molecular Medicine
The first phase of the ambitious international effort to determine the entire sequence of the human chromosome set is virtually complete. Human Genome Project scientists plan to finish the human sequence by 2003, along with a database of the most common sequence variations that distinguish one person from another. This knowledge base, freely available to any interested person over the Internet, will revolutionize biology and medicine.
136). Genetic Privacy Task Force Hears Testimony
The Task Force on health Records and Genetic Privacy, established in 1997 by the Commerce Committee of the U.S. House of Representatives, held its first meeting on July 22 in Washington, D.C. cochaired by Reps. Cliff Stearns (R-FL) and gene Green (D-TX), the eight-member bipartisan task force is considering the following issues as a prelude to establishing policy:
* Effects on Americans of the many genetic tests created as a result of the Human Genome Project.
137). Testing Panel Emphasizes Education
A 14-member nongovernmental panel convened by NIH in April 1997 recommended that genetic testing for mutations that cause cystic fibrosis (CF) be offered to all pregnant couples, those planning a pregnancy, those with a family history of the disease, and partners of people with CF. The panel did not endorse genetic testing of newborns because current research does not show a benefit.
138). Creating and Comparing DNA Profiles
Only one-tenth of a single percent of DNA (about 3 million bases) differs from one person to the next. Scientists can use these variable regions to generate a DNA profile of an individual, using samples from blood, bone, hair, and other body tissues and products.
In criminal cases, this generally involves obtaining samples from crime-scene evidence and a suspect, extracting the DNA, and analyzing it for the presence of a set of specific regions of DNA (markers).
139). ELSI Working Group Under Review
An 11-member committee was appointed in June to review the function and structure of the NIH-DOE Joint Working Group on the Ethical, Legal, and Social Implications (ELSI) of Human Genome Research. As planning begins for the next 5 years, NIH and DOE Human Genome Program staff consider this an appropriate time to determine how best to provide for objective advice on ELSI issues.
140). ELSI Task Force Seeks Genetic-Testing Experiences
The Task Force on Genetic Testing, part of the DOE-NIH Working Group on Ethical, Legal, and Social Implications of Human Genome Research, is examining the development and provision of genetic tests in the United States. The task force seeks to learn about specific experiences, both good and bad, of laboratories providing tests and of physicians, genetic counselors, nurses, consumers, and others who order or receive test results.
141). Notre Dame Conference Explores ELSI Issues
An international, interdisciplinary conference on Controlling Our Destinies: Historical, Social, Philosophical, and Ethical Perspectives on the Human Genome Project was held at the University of Notre Dame (UND) on October 5-8, 1995. Sponsored by the John J. Reilly Center for Science, Technology, and Values with assistance from DOE, the conference was designed to create a dialogue on specific and general issues as related to the Human Genome Project.
142). Association Considers Genetics, Justice, Minorities
With a program entitled "DNA: Genetics, Criminal Justice, and the Minority Community," a large professional association considered for the first time the implications of genetics for law enforcement and civil rights. On September 23-24, 1994, the Justice George Lewis Ruffin Society of Massachusetts marked its tenth anniversary by bringing Boston law-enforcement representatives together with minority professionals to examine issues of genetics; race; criminal behavior; and civil discrimination in employment, insurance, and health care.
143). Chlamydia Genome Offers Surprises
Analysis of the 1-Mb genome of Chlamydia trachomatis has revealed some unexpected biology for the tiny organism. C. trachomatis is responsible for causing the most common bacterial sexually transmitted disease (STD) in the United States as well as trachoma, a major cause of blindness in Asia and Africa. A collaboration among scientists at the University of California at Berkeley and Stanford University, the study was reported in the genome issue of Science (October 23, 1998).
144). Helix Directory Lists Testing Laboratories
Since August 1993, Helix: A Directory of Medical Genetics Laboratories has been fulfilling clinician requests for names of laboratories that perform molecular genetic testing. The only resource of its type in North America, Helix was started by clinical geneticist Roberta A. Pagon (University of Washington), who recognized the need of genetic professionals for a centralized, computer-based directory of clinical and research genetic laboratories.
145). Cancer Gene Web Site Set to Debut
The Cancer Genome Anatomy Project (CGAP) of the National Cancer Institute (NCI) is set to go online (http://www.ncbi.nlm.nih.gov/CGAP/) with the first installment in its cancer gene catalog. The goal of CGAP, which began last year, is to develop new diagnostic tools based on understanding molecular changes that underlie all cancers. These tools eventually will help doctors develop and select treatments designed to fight specific cancers.
146). OMIM Catalogs Human Genes and Genetics Disorders
Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative, and up-to-date human gene and genetic disorder catalog that supports medical genetics and the Human Genome Project. The print version, Mendelian Inheritance in Man (MIM), was started in the early 1960s by physician Victor McKusick [Johns Hopkins University (JHU)] as a catalog of X-linked traits.
147). New Five-Year Plan in Process as HGP Passes Midpoint
Midlife traditionally presents an opportunity for making evaluations, as progress toward milestones is measured and courses are altered. So, too, with the Human Genome Project (HGP), the massive 15-year biological undertaking begun in 1990 to obtain the sequence of all 3 billion bases in human DNA. Rapid progress and technology developments during the first half of the project have affirmed researchers optimism that the task can be completed on time and within budget.
148). DOE Contractor-Grantee Workshop Sequencing Technologies
One of the genome project's major challenges is the need for increased automation in DNA-sequencing technologies to increase speed and reduce costs. Standard methods based on gel-electrophoresis separation of nested fragment sets are considered too slow and expensive. Progress in automation ranges from enhancements of conventional gel-based technologies to novel, gel-less, automatable approaches.
149). High-Resolution Physical Maps of Chromosomes 16 and 19 Completed
Chromosome 16.
The LANL integrated chromosome 16 map announced at the Santa Fe workshop is composed of a cytogenetic breakpoint map, a low-resolution physical map in mega-YACs, and a high-resolution physical map in cosmids and mini-YACs. Over 600 genes, DNA markers, and microsatellite repeats generated by investigators worldwide have been integrated into the new map.
150). NIH Advisory Council Meets
The NIH National Advisory Council for Human Genome Research was convened for its twelfth meeting on September 22, 1994, in Washington, D.C. Francis Collins, Director of the NIH National Center for Human Genome Research (NCHGR), presided. Selected highlights of the meeting follow.
Jeffrey Trent, Scientific Director of the NCHGR Division of Intramural Research, updated the council on the division's activities.
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