Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News, Nov. 1994; 6(4):6
Los Alamos National Laboratory
LOS ALAMOS NATIONAL LABORATORY (LANL)
- (DOE, established 1988)
- ROBERT K. MOYZIS, Director
- Larry L. Deaven, Deputy Director
- CONTACT: Lynn Clark, Technical Coordinator (505/667-9376, Fax: -2891; clark@telomere.lanl.gov); LANL; Center for Human Genome Studies, MS M886; Los Alamos, NM 87545.
OTHER KEY RESEARCHERS
- Michael Altherr
- Norman Doggett
- Joe Gatewood
- Deborah Grady
- Jim Jett
- Dick Keller
- Jon Longmire
- Pat Medvick
- Julie Meyne
- Rob Pecherer
- David Torney
- Michael Yesley
MAJOR GOALS
- Assembly of complete, high-resolution (<10 kb), sequence-ready chromosome 16 map; low-resolution (0.5 Mb) map of chromosome 5; and high-resolution, sequence-ready map of Cri du Chat region on chromosome arm 5p.
- Determination of molecular basis of chromosome structure and function and isolation of selected disease genes on chromosomes 5 and 16.
- Short-term development and support for large-scale physical mapping and sequencing projects and long-term development of tools for storage, manipulation, and analysis of genome data.
- Development and application of new methods for physical mapping and sequencing; use of robotics in handling and storing DNA fragments; construction of DNA libraries from flow-sorted chromosomes; and rapid, inexpensive, large-scale sequencing.
- Studies of ethical, legal, and social issues arising from the increased availability of genome data.
- Transfer of technologies and medically important information to industry and the medical community.
- Establishment of Internet access via WWW and Mosaic to physical mapping data.
MAJOR ACCOMPLISHMENTS
- Construction of integrated chromosome 16 physical-genetic-cytogenetic map, including:
- low-resolution yeast artificial chromosome contig map providing nearly complete coverage of euchromatin; map consists of 350 sequence tagged sites, 600 Centre d'Etude du Polymorphisme Humain mega-yeast artificial chromosomes and 220 flow-sorted chromosome 16-specific yeast artificial chromosomes that are localized to and ordered within a somatic cell hybrid breakpoint map (1-Mb average resolution); and
- a high-resolution, sequence-ready, fingerprinted cosmid contig map covering 60% of chromosome 16 and anchored to yeast artificial chromosome and breakpoint maps via sequence tagged sites developed from cosmid contigs and by hybridizations between yeast artificial chromosomes and cosmids.
- Construction of human chromosome 5 framework sequence tagged site map consisting of 306 markers; of these, 60 were assigned regionally on the p arm at a 1-Mb resolution [Joan Overhauser (Thomas Jefferson University)], and 100 were assigned regionally on the q arm at a 1.5-Mb resolution [John Wasmuth (UC Irvine)].
- Biological developments, including (1) identification and cloning of the human telomere; (2) determination of unusual 3-D structure of telomeric DNA [with Alex Rich (Massachusetts Institute of Technology)]; (3) identification and cloning of highly conserved centromeric repetitive DNA regions, likely human centromere Components; and (4) fluorescence in situ hybridization technique enabling physical orientation of probes.
- Development of technology, including (1) National Laboratory Gene Library Project (with LLNL) chromosome-specific libraries: over 2600 DNA libraries sent to research and production laboratories worldwide, including complete digest libraries for each human chromosome; partial-digest phage and cosmid libraries for human chromosomes 4, 5, 6, 8, 10, 11, 13, 14, 15, 16, 17, 20, X, and Y; and complete digest low-chimeric yeast artificial chromosome libraries for human chromosomes 5, 9, 16, and 21; (2) flow-cytometry techniques for DNA fragment sizing and detecting single DNA molecules, resulting in a Cooperative Research and Development Agreement with Life Technologies, Inc. for codevelopment of rapid DNA-sequencing technology; (3) robot for high-density cosmid-yeast artificial chromosome array replication and distribution; and (4) parallel primer walking directly off cosmid contig clones.
AVAILABLE RESOURCES
- Phage and cosmid libraries developed within National Laboratory Gene Library Project (see accomplishments).
- Centre d'Etude du Polymorphisme Humain Mark II to VII yeast artificial chromosome libraries.
- Sequence tagged site collections for chromosomes 16 (320) and 5 (306).
- SIGMA, a graphical map editor.
- cDNA Inform database and software for comparison of sequences.
- Modified Biomek robot and LANL robot for high-density array construction.
- Graduate and postdoctoral research training through LANL and DOE Human Genome Distinguished Postdoctoral Fellowship (LANL: -5919; Oak Ridge Institute for Science and Education: 615/576-9975).
- URL: http://www-ls.lanl.gov
HGMIS staff
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The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v6n4).