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Uman Enome News uman enome news ISSN: 1050-6101 Vol. 6, No.3, September 1994 Managing Genome Sequence Data Collaborative Databases Serve Worldwide Research Community s technology improves and information accumulates exponentially, continued progress Historical Ain the Human Genome Project will depend increasingly on the development of sophisti­ cated computational tools and resources to manage and interpret data. Various systems now Perspective, manage data relevant to genome research; these systems range from highly specialized Current Status, databases supporting local research projects to general databases serving the entire inter­ Future national community both as repositories and analysis resources that guide ongoing research. Challenges Examined Public databases containing the nucleotide Database growth is accelerating rapidly, with sequences of the complete human genome and more than half the sequences having been of selected model organism genomes will be a added in the last 2 years. This number is major product of the Human Genome Project. expected to rise dramatically within the next The ease with which researchers can retrieve decade to about 10 billion bp. As more genes and use the data from these and other related are identified and sequenced and understanding databases will provide one measure of the of sequence data improves, databases will play projecrs success. an increasing role in capturing new knowledge and making it accessible. Although much progress has been made in data­ base development and operation, many chal­ Sequence Database History lenges remain in collecting, organizing, storing, and distributing data. As maps and sequences The Los Alamos Sequence Ubrary was estab­ accumulate and the focus shifts from data gen­ lished in 1979 at the DOE Los Alamos National eration to analysis, new challenges will arise. Laboratory (LANL) to store DNA sequence data Some feel that a key task will be to link the vari­ in electronic form. At about the same time, data­ ous biological databases into a loosely coupled base activities were beginning at EMBL, and distributed alliance so researchers around the world can explore all relevant facets of a particu­ lar topic. Research and development for these interoperable databases demand the close inter­ action of biologists with mathematicians, soft­ In This Issue... ware engineers, and programmers to develop Page Genome News the needed software, database tools, opera­ 1 Managing Genome Sequence Data tional infrastructure, and algorithms. 2 Breast Cancer Gene Found 5 Whitehead, Genethon Groups Present New Linkage Map Four major nucleotide sequence databases now 7 OHER Launches Microbial Genome Initiative store almost 200 million bp representing human and more than 8000 other species. The four are 7 Evans Moves NIH Genome Center to Dallas GenBank® and Genome Sequence Data Base 8 DOE Biomarker Workshop Meets In Santa F. (GSDB) in the United States, European Molecu­ 10 DOE ELSI Program Enters Fifth Year lar Biology Laboratory (EMBL) Nucleotide 11 GDB Forum: Medllne Citations; Graphicallnte/faces; Sprintnet Sequence Database, and the DNA Data Bank of Access; OMIM on WWW; User Support, Registration, Training Japan (DDBJ). Each group collects a portion of 12 Chromosome 16 Mappers Review Status the total sequence data reported worldwide, often 13 Chromosome Editors (Nomenclature Committee) procesSing submissions and update requests For Your Information within 48 hours. Because they exchange new 3 Resources (see s/so p. 7) and updated sequences frequently-usually 6 Publlcalfons (see ./50 p_ 13) daily-the databases contain the same 14 Catendars of Genome-Related Events, Training sequences, each in its own format. All four of these evolving databases are working to 15 Funding Announcements, Guidelines for U.S. Genome Research improve data design and quality. 16 Subscrlption/Document Request; Selected Acronyms 2 Human Genome News, September 1994 Genome News discussions began in 1982 on collaborations The LANL data library evolved into the data­ between the two institutions. From these early base GenBank when in 1982 Bolt, Beranek, days, EMBL and LANL agreed that any data sub­ and Newman (BBN) became the primary con­ mitted to or entered by one group would be for­ tractor lor distribution of data and user support. warded immediately to the other, thus avoiding LANL became a subcontractor to BBN, provid­ duplication of effort. As other sequence data­ ing data collection and deSign. Sequence data bases joined the collaboration, data sharing was activities at BBN and LANL were funded by the extended to them. NIH National Institute of General Medical Sci­ ences (NIGMS) with support from DOE and other agencies. At the end of the first 5-year con­ tract, IntelliGenetics became the primary contrac­ tor, with LANL again as subcontractor charged with designing and building the database. Breast Cancer Gene Found With the conclusion of the second S-year con­ tract in October 1992, NIGMS transferred its team of some 45 researchers led by Mark Skolnick (Univer­ responsibility for the GenBank project to the Asity of Utah Medical Center and Myriad Genetics, Inc.) and National Center for Biotechnology Information Roger Wiseman (NIH National Institute 01 Environmental Health (NCB I) at the National Library of Medicine. Sciences, North Carolina) reported on September 14 the isolation NCBI, directed by David Lipman, had been of the BRCA 1 gene. Defective forms 01 BRCA1 are thought to created in November 1988 to develop auto­ cause predisposition to certain inherited forms of breast and ovar­ mated information systems for supporting ian cancer. Scientists have been searching for BRCA 1 in a 600-kb biotechnology and molecular biology and to region since 1 990, when Mary-Claire King's group (University 01 conduct basic research in computational molecular biology. LANL continued to handle California, Berkeley) demonstrated a pattern 01 genetic markers in all direct GenBank submissions and updates families where breast cancer occurred unusually early and frequently. through a DOE-NIH interagency agreement. Two papers describing the discovery appear in the October 7 issue of In August 1993 the data resources at LANL and Science, and a separate study on the approximate location of another NCBI became independent of each other, with gene associated with breast cancer-BRCA2-was published in the both providing collection and distribution serv­ September 30 issue. The 100-kb BRCA 1 gene is composed of 21 coding ices and continuing to enhance access and exons midway between markers D17S1321 and D17S1325 on the chro­ usability of the databases. The GenBank data­ mosome 17 long arm. Isolation of this gene could lead to significant clues base remained at NCBI, and the LANL service about the risk of developing cancer, not only of the breast and ovaries, but also of the colon and prostate gland. led by Michael Cinkosky took the new name of Genome Sequence Data Base (GSDB). GSDB Although these discoveries are considered very important for studying the recently moved to the National Center for disease and eventually developing new diagnostic tools and treatments, Genome Resources (NCGR) in Santa Fe, New scientists warned that much work lies ahead. NIH Director Harold Varmus Mexico, which focuses on the development of said at a press conference that breast and ovarian cancers are extremely resource projects to support public and private complicated diseases that are probably affected by various genetic and genome research. environmental factors. Several NIH entities, led by the National Center for Human Genome Research, have recently awarded research groups more The EMBL Nucleotide Sequence Database was than $2.5 million to study breast cancer testing and the social, psychologi­ established in 1982 as the EMBL Data Library cal, and economic implications of such tests. in Heidelberg, Germany. Directed by Graham Cameron, the database is now maintained and More than 45,000 U.S. women and 300 men died of breast cancer last distributed by the European Bioinformaticslnsti­ year. BRCA 1 is linked to about 5% of the 180,000 breast cancer cases tute (EBI), a new EMBL outstation at Hinxton diagnosed annually in the United States and to 25% of those in women Hall near Cambridge, U.K. The Sanger Centre under the age of 30. About 600,000 U.S. women and millions around the and the Medical Research Council's Human world may carry BRCA1 mutations. Genome Mapping Program Resource Centre Tumor Suppressor are also located at the site. In addition to the Nucleotide Sequence Database, EBr maintains BRCA 1 is believed to act as a tumor suppressor regulating cell growth and division. II suppressor genes are lost or damaged by mutation, uncon­ and distributes the SWISS-PROT Protein trolled cell growth can occur, resulting in cancer. Researchers reported Sequence Database in collaboration with finding several different mutations in all family members who inherited the Amos Bairoch (University of Geneva) as well faulty BRCA 1 gene and in those who developed breast cancer at an early as more than 30 other specialty databases. age; they also observed the mutation in many women with both breast DDBJ was created in 1984 and began operat­ and ovarian cancers. Before diagnostic tests can be developed to detect ing independently in 1986 with the sponsorship the aberrant gene, each specific mutation must first be identified. of the Japanese Ministry of Education, Science, Although inheriting a mutated BRCA 1 gene was found to increase dramati­ and Culture and representative
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