uman enome news

ISSN:l050-6101 Vol. 3, No.1, May 1991 DOE Holds Contractor-Grantee Workshop Physical Mapping Efforts Going Well; Gels Increasing Sequencing Efficiency

he DOE Human Genome Prograll1 held its second Contractor-Grantee Workshop Charles R. Cantor and HGMIS gratefully Tin Santa Fe, New Mexico, on February l7-W. More than 200 program-sponsored acknowledge contribu­ scientists attended the meeting, in addition to invited guests and industry represen­ tions to this article by tatives. DOE-supported human genome research projects are conducted at 7 DOE Elbert W. Branscomb, national laboratories (including its 3 human genome centers), 37 major universities, Anthony V. Carrano, and 32 companies through collaborations and awards. Projects were represented by Leroy E. Hood, oral presentations or posters. Robert K. Moyzis, and Robert J. Robbins. Six platform sessions focused on the more focus is needed on the immediate following: informatics needs of ongoing biology projects. • physical mapping progress, Many parallel efforts under way in cloning, • large DNA fragment cloning, informatics, mapping, and sequencing will • strategies for preparing samples for further improve the technologies required for efficient DNA sequencing, genomics. Program participants feel that this situation is healthy at present and that a few • new methods for a variety of genome efforts, • DNA sequencing instrumentation, and In This fssue .•. • database and computer algorithm needs for existing or projected genome Page Genome News research. 1 DOE Holds Contractor-Grantee Workshop David Galas, Associate Director, Office of 5 LANL, Life Technologies Approve CRADA Health and Environmental Research (OHER), 6 Conncil on Competitiveness Urges Action spoke about the relationship between the 7 Moore Calls Tech Transfer Critical to Fntnre' Human Genome Program and other OHER 8 NIH Discusses eDNA Role with Invited Group programs. Michael Yesley [Los Alamos 9 NCHGR Advisory Council Holds First Session National Laboratory (LANL)] presented ethi­ 9 NIH PACHG Appoints New Members, Chair cal,legal, and social issues pertaining to data produced in the genome project. 10 DOE·NIH Establish Mouse Working Group Meeting Reports The general impression conveyed by most 11 WorkshOp on Mouse Genome Mappiug presenters was that physical mapping efforts are going well; chromosomes 16, 19, and 13 Second X Chromosome Workshop portions of 11 are now well covered with Resources large numbers of assembled cOntigs. Fluo­ 14 Nouprofit Resource Centers Facilitate Mapping rescence in situ hybridization (FISH) is 18 Genome Literature Abstracts emerging as an extremely effective method for ordering cloned probes. For Your Information 19 U.S. Genome Research Funding Information Fractionating DNA fragments is becoming 20 Genome-Related Tutorials OlTered much faster with capillary or thin gel slab 21 Calendar of Genome Events electrophoresis. Informatics support for most 22 Training Calendar: Worksbops and Coursework physical mapping efforts and for large-scale DNA sequencing remains problematic, and 24 Acronym List, Subscription/Document Request 2 Human Genome News, May 1991

approaches will emerge as those most likely explained this method and showed the DOE Program Report to accelerate the project. usefulness of FISH in characterizing chro­ Update mosomal rearrangements. HGMIS is preparing One theme that recurred frequently during Glen Evans (Salk Institute) and collabora­ the 1991 revision of the the 3-day meeting was the rapid change in DOE Human Genome bottlenecks or rate-limiting steps, particu­ tors have used a combination of methods larly in DNA-sequencing efforts. Advances in mapping chromosome 11. In construct­ 1989~90 Program Report. in raw sequencing speed make automated ing several multimegabase contigs of To update the report production of DNA samples and melding of cloned DNA segments, Evans used a YAC and accurately reflect raw sequence reads increasingly important. as a hybridization probe against a filter DOE-funded genome array of cosmids to identify covered cos­ research projects, .. Physical Mapping mids. Given the appropriate libraries, a HGMIS asks investi­ Generally, impressive progress continues in gators to send abstracts, series of overlapping clones for 1- to 2-Mb photographs, and the construction of physical maps of selected regions apparently can be isolated in a fignres. Investigators human chromosomes. Yeast artificial chro­ matter of weeks. who have not already mosomes (yACs), though not without prob­ lems, are proving helpful in linking cosmid Both the chromosome 19 program at LLNL submitted this material and that of chromosome 16 at LANL have are reminded to forward contigs or providing rapid initial coverage of a region. collected about two-thirds of their chromo­ it to: somes into cosmid contigs. A variety of HGMIS The powerful new FISH technique is providing very effective automated approaches are Oak Ridge National mapping data at several levels of resolution, being used to expand and link these con­ Laboratory extending from metaphase chromosomes. tigs. Existing maps are dense enough to be p.o. Box 2008 It offers a rapid and accurate method of useful to investigators wishing to locate Oak Ridge, TN regional clone assignment to a chromosome genes on these chromosomes; about 80% 37831-6050 band. Barbara Trask [Lawrence Livermore of randomly picked probes will fall on con­ National Laboratory (LLNL)] showed that tigs or clones already mapped. To aid such much higher resolution mapping can be studies, a series of anchor points has been achieved with interphase cells; once markers established between the current genetic are known to be close, their relative order and physical maps. No clone-order dis­ can be determined and distances estimated crepancies are evident between the two in the 50-kb to 1-Mb range. map types for either chromosome. The presence of a selectable marker near Excellent progress is being made wtth maps the long-arm telomere of chromosome 16 of X-chromosome regions. Thomas Caskey, made possible the construction of a set David Nelson, and their coworkers (Baylor of hybrid cell lines particularly convenient College of Medicine) are focusing on several for that chromosome. Grant Sutherland (Ade­ areas that contain genes of interest rather laide Children's Hospital, South Australia) than attempting to construct a complete

DOE Human Genome Program staff (I. to r.) Charles Cantor Denan Wang (Lawrence Berkeley Laboratory Human (Principal Scientist), Robert Robbins (Informatics Detail .. Genome Center) explains her poster to DOE Human to DOE from tbe National Science Fonndation), and Genome Coordinating Committee (HGCC) member Benjamin Barnhart (Program Manager) view posters at tbe Anthony Carrano (Director, LLNL Human Genome Contractor-Grantee Workshop_ Center). Human Genome News, May 1991 3

map of this large chromosome. Caskey Berg (Washington University School of described the potency of using tandem Medicine) and his group have exploited the simple sequence repeats as genetic markers. bacterial Tn5supF transposon system by inserting a known 260-bp sequence into In the next few years, nearly complete contig lambda clones to serve as the priming site maps should be obtained on chromosomes for sequencing. This procedure eliminates 11,16,19, and X. the need to subclone large inserts, since III large-Insert Cloning Vectors sequencing could be accomplished directly from the lambda clone by primer walking Several groups reported new approaches from the inserted transposon. Claire Berg toward large-insert cloning vectors: (University of Connecticut) described the • Peter Hahn and his colleagues (State use of transposon yo (Tnl 000) to sequence Sylvia J. Spengler, University of New York, Syracuse) plasmid inserts. Robert Weiss and Raymond Executive Officer, employed double-minute chromo­ Gesteland (University of Utah) reported on HGCC, organized somes as megabase-cloning vehicles. applying this method to sequence p1asmids the DOE Contractor­ • Jean-Michel Vos (University of North containing 10-kb inserts. Their clone-pooling Grantee Workshop in Carolina, Chapel Hill) suggested the scheme is employed for rapid mapping of Santa Fe, New Mexico. Epstein-Barr virus as a cloning vehicle. the transposon integration sites; the mapped • Hiroshi Shizuya (Melvin Simon's transposons are then used as primer sites for multiplexed dideoxy sequencing. Reece Hart (Salk laboratory, Calffornia Institute of Tech­ Institnte) tries out the nology) described a new cloning sys­ William Studier (Brookhaven National lab­ online DOE Human tem using Escherichia coli and ITS oratory) reported on priming DNA sequenc­ Genome Information plasmid F factor. ing reactions by using sequences within the Database, assisted by • Philip Youderian (California Institute insert itself. George Church (Harvard Medi­ Beth Owens (HGMIS, of Biological Research) discussed a cal School) presented the status of his Oak Ridge National Laboratory). set of "stealth" vectors that carry an developments for computer-assisted mUlti­ S replicon, the Salmonella phage B-22 plexed sequencing. Arthur Riggs (Beckman early region, and a chloramphenicol Research Institute) described a ligation­ resistance determinant. The vectors mediated genomic sequencing strategy that can accept DNA inserts of several allows sequence information to be derived hundred kilobases, maintain them in from genomic DNA without subcloning. a single copy, and then amplify them III New Techniques for DNA Sequencing about 500-fold. Gary Hermanson (Glen Evans' laboratory, Bruce Jacobson (Oak Ridge Salk Institute) gave an interesting presenta­ National Laboratory) and tion on isolating the ends of YAC inserts by Heinrich Arlinghaus homologous recombination, a promising tech­ (Atom Sciences, nique for walking within YAC libraries. Sherman Inc.) are implement­ Weissman (Yale University) reported on his ing tin, iron, and group's efforts to achieve normalized cDNA libraries from human thymus. The research is proceeding well in setting the stage for large­ \ scale sequence analysis of the corresponding cDNAs from various tissues. III DNA Sequencing Methodology Lauren Sears and A goal of the Human Genome Project is to Ted Davis (New reduce DNA sequencing costs. While con­ England Biolabs, siderable attention has been given to data­ Inc.) discuss collection instrumentation and data-analysis strategies. hardware and software, the scientists felt that more emphasis is needed on technologies that will reduce costs by increasing through­ put and template quality. A number of presentations dealt WITh trans­ poson insertions to assist in DNA sequencing, thereby minimizing redundancy associated with shotgun cloning strategies. Douglas 4 Human Genome News, May 1991

DOE Workshop lanthanide isotopes as reporter groups for This technique uses biotinyiated primers in Presentations DNA sequencing. Sputter-Initiated Reso­ standard sequencing reactions. Richard Reflect Progress nance Ionization Spectroscopy or Laser Mathies and Alexander Glazer (UniverSity Complete report, Atomization Resonance Ionization Spectros­ of California, Berkeley) demonstrated ana­ including abstracts, copy (two forms of mass spectrometry used lytical miniaturized fractionations of fluo­ available on request to assay these reporter groups), appearto rescing DNA fragments under a confocal from HGMIS (see have striking sensitivity and speed of analy­ laser microscope system. request form, p. 24). sis. The thin-layer capillary electrophoresis techniques reported by Barry Karger (North­ Two novel methods are being developed as eastern University) present notable opportu­ third-generation sequencing approaches. Joe Gray (LLNL) and coworkers are explor­ nities for speeding up throughput in the analysis of DNA sequence fragments. The ing the use of X-ray diffraction for DNA impressive data of Uoyd Smith (University sequence analysis. Radoje Drmanac and of Wisconsin) suggested that thin-layer capil­ Radomir Crkvenjakov (Argonne National lab­ lary gels will work effectively in sequencing­ oratory) described sequencing by hybridi­ fragment separation and provide multiple­ zation: short oligomers (8 to 9 mers) with lane parallelism for DNA sequence analysis. known sequence are hybridized to short The use of exonucleases and the ability to fragments of DNA with unknown sequence. detect single nucleotides for the analysis of The collection of oligomers that hybridize single DNA molecules are being advanced to a fragment reveal the sequence. The by Richard Keller's (LANL) group. (See group has successfully sequenced a small associated article, p. 5.) DNA segment and is now scaling up for practical applications. Linda Strausbaugb and Claire Berg (University Several presentations were made on scan­ of Connecticut) present ning tip microscopy. An outstanding one • Informatics their poster at the DOE by Rodnell Balhorn and Wig bert Siekhaus Presentations showed broad progress in Contractor-Grantee (LLNL) used scanntng tunneling microscopy applying computer technology to the Human to reveal images of monolayers of adenine Workshop in Santa Fe, Genome Project. Jim Fickett (LANL) and New Mexico. and thymine bases that are consistent with colleagues noted that the chromosome 16 the known physical map requires management of nearly a mil­ structure of these lion data items, the bulk from fingerprint­ molecules. ing about 4000 clones. With over 60% of Other presenters chromosome 16 covered by cosmid con­ described methods tigs, attention is shifting to YACs, FISH, and for detecting DNA for sequence tagged sites (STSs) for closing e~her sequencing or intercontig gaps, thereby requiring exten­ mapping. Christopher sions to the existing data system. Chris Martin and Irena Fields (New Mexico State University) and BrQnstein (Tropix, Inc.) colleagues described an automated system demonstrated the for screening candidate STS sequences and application of chemi­ predicting good polymerase chain reaction luminescence in priming sites on them. Sanger dideoxy Many posters and one presentation sequencing protocols. addressed the central computing problem of sequence matching. Eugene Lawler Eliezer Huberman discussed a new dynamic programming (Argonne National method developed w~h Will iam Chang (both Laboratory), Raghbir at Universny of CalHornia, Berkeley) that is Atbwal (New Jersey Medical School), 4 or 10 times faster (using nucleotide or Arbansjit Sandhu amino acid sequences, respectively) than (University of Medi­ the best previous dynamic programming cine and Dentistry algorithm. of New Jersey), and Providing and controlling access to multiple David Callen (Adelaide Children's Hospital) data sources is a key challenge for genomic (I. to r.) enjoy discus­ research. Thomas Slezak (LLNL) reported sions during a poster on some proof-of-concept tests that showed session. how controlled, multiple database access (see DOE, p. 5) Human Genome News, May 1991 5

LANL, Life Technologies Approve CRADA First for u.s. Human Genome Project t a signing ceremony on March 21, A representatives from Los Alamos National Laboratory (LANL) and LHe Tech· nologies, Inc., (LTI) approved a Cooperative Research and Development Agreement (CRADA), the first between a DOE human genome center and a private·sector corpora­ tion. This CRADA is also the first for LANL, for DOE defense-oriented laboratories, for the DOE Albuquerque operations office, and for the U.S. Human Genome Project. The 3-year agreement calls for investigators from LANL and LTI to cooperate in develop­ ing faster and cheaper techniques for deter­ mining the base sequence of the human genome in much longer DNA fragments than now possible. This effort would be difficult for either team alone, and the collaboration promises to be fruitful for both parties. No W. Henson Moore, Deputy Secretary of Energy; John Whetten, LANL Associate Director for Energy and Technology; and J. Stark Thompson, money will change hands between the two LT! President and CEO, (seated I. to r.) signed the first CRADA of the organizations. LTI will have the first oppor­ Human Genome Project on March 21. Others participating are (I. to r.) tunity to license any products resulting from Linda Stuntz, Deputy Under Secretary of Energy; Representative Joe the joint effort and would pay royalties to Skeen (R-N.M.); Representative Bill Richardson (D-N.M.); Senator JelT LANL under such a license. Bingaman (D-N.M.); Representative Constance Morella (D-Md.); and Senator Pete Domenici (R-N.M.). A mission of the DOE Human Genome Program is to transfer technologies government and ind ustry researchers to developed in research laboratories to the work together to advance scientific knowl­ private sector. This CRADA. an example edge and, equally important, to apply it in of basic science and applied technology practical technologies to benefit the Ameri­ moving forward simultaneously, will set can people and the American economy." the stage for increased industry access to laboratory technology and will help govern­ The United States is considered outstand­ ment laboratories d raw on private-sector ing in developing technology but not in resources. transferring it from federal organizations to the private sector. An innovative response by In announcing the pact, Deputy Secretary Congress to the growing challenge of U.S. of Energy W. Henson Moore said, "This agree­ competitiveness, CRADAs are designed to ment signifies a new partnership between make the laboratories more user friendly, facilitate technology transfer, and foster economic competitiveness by encouraging laboratory-industry partnerships. DOE (from p. 4) In addition to providing an important vehicle can be achieved by using client-server archi­ to leverage research dollars, CRADAs help fulfill the vision of national laboratories solv­ tecture found in most commercial, multiuser ing complex, nationally important problems database systems. Peter Pearson (Johns by demonstrating that investing in science Hopkins University) described the public can ultimately impact competitiveness. Sev­ database efforts under way with the Genome eral more CRADAs are now being planned, Data Base (GDB) project (sponsored by the and DOE committed to moving quickly and Howard Hughes Medicallnslitute). He also is efficiently into future agreements. discussed collaborations with LANL and LLNL for sharing physical mapping data and the The authority to enter into CRADAs was possibility of researchers viewing laboratory­ extended to DOE contractor-operated generated map data in the information-rich laboratories through the National Competi­ context of GDB. ¢ tiveness Technology Transfer Act of 1989, 6 Human Genome News, May 1991

LTI Says CRADA cosponsored by New Mexico Senators label a single DNA strand WITh four different Will Increase Pete Domenici and Jeff Bingaman. "Human fluorescent, base-specific tags; an exonucle­ Research Pace gene mapping holds tremendous potential ase is then used to cut the labeled nucleic for improving the quality of lITe for so many," acid base pairs from the DNA (see figure). said Domenici, who envisioned research To determine the DNA base sequence, the partnerships among the laboratories, busi­ individual labeled bases are induced to nesses, and universITies to work on projects fluoresce in one of four colors as they pass DNA Rapid Sequencer being developed by such as human genome, high-temperature sequentially through a focused laser beam. LANL and LTI. If suc­ superconductivity, and semiconductors. The bases can be identified and counted by a sensitive photodetector. cessful, the technology The research described in the agreement will allow sequencing will use an LTI-modified DNA polymerase to The most commonly used commercial of 50,000-bp DNA frag­ ments at 1000 bp/s. sequencing methods can handle only short DNA fragments of about 500 bp. If Cutting this new technology proves successful, Enzyme researchers will be able to sequence frag­ ments at least 100 times longer. A team of One, Dye-Labeled, LANL researchers, led by Richard Keller DNA Molecule - 50,000 Nucleolides and funded by the DOE Human Genome Program, will offer expertise in physical .. ~ IndiVidual Dye-Labeled ______chemistry, detection technologies, instru­ Nucleotides (single molecule) ------... mentation, and DNA handling to bring to ~ fruition a novel DNA sequencing technique Stream of patented by several LANL scientists. Water Photo-Detector (laminar flow) The LTI scientists, led by John Harding (4 channels) since 1989, will concentrate on developing Discriminator 1 Output the new enzymes and modified nucleotides String essential for sequencing DNA with the new Laser technology. Harding's research efforts GA neG -€::!=J:jJ • L.-...Ftt~ have centered on creating new tools and Time applying existing ones to analyze and map Merge Prism Correlator mammalian genomes.

. Council on Competitiveness Urges Action To Strengthen Performance The United States' based on an analysis • .u.S.lea~r~p generic technologies, leading businesses, once-commanding of 94 technologies in m many cr1tlcal the U.S. ability to organized labor, and lead in the critical 9 major economic technologies has compete will erode higher education, technologies dri'l'ing sectors that together been slipping and, further, with serious whose goal is to economic grow1h and account for sales of in some cases, has consequences for jobs, improve the ability of national security is more than $1 trillion. been lost alto/lether. economicgrowth,and U.S. industry and its Other countnes being challenged by The report lists several national security. The workers to compete in international competi­ are systematically report recommends a world markets. key findings, including achieving leader­ tion, according to a the following: series of actions for Full copies of the new report by the ship in many critical government, industry, • The critical generic technologies . report may be Council on Competi­ and universities to obtained for $20. <> tiveness. technologies that eAmerica's research strengthen the will drive economic universities consti­ country's perfor­ Gaining New Ground: W,'owth and compet­ tute a great national Technology Priorities mance. One recom­ Itiveness over the asset, but their mendation is that for America's Future is next decade already focus on technology Contact: the result of a 2-year technological leader­ exist, and industry and competitive­ ship become a CQuncil on effort guided by a needs to improve its ness is limited. Competitiveness ability to convert national priority. group of technology The report concludes 900 17th Street mY, experts from industry, them into market­ The Council on Suite 1050 universities, and labor able productsand that, unless the nation Competitiveness is a acts to enhance its Washington, DC 20006 from around the services. nonprofit coalition of 202nSS-3990 country. The report is position in critical chief executives from Human Genome News, May 1991 7

"It's high risk, high payoff. If we can make it LTI President and Chief Executive Officer For more work, it will improve sequencing rates by J. Stark Thompson stated, "We are confi­ information on the several orders of magnitude. We're shooting dent that our agreement with Los Alamos LANL-LTI CRADA, for about 1000 base pairs a second, com­ will lead to the development of products contact: pared with current commercial sequencing that will significantly move forward the pace Mary Fraker, LTI rates of less than 10,000 base pairs a day," of human genome research. An added 301/840-4097 Keller said. The projected rate of 1000 bp/s benefit is that these results will strengthen John Webster, LANL is derived from enzymatic rates of cleavage the nation's biotechnology industry in the 505/667-7000 and rates of detection. world marketplace." Through its BRL and GIBCO brands, LTI is Operated by the University of CalHornia for a leading supplier worldwide of molecular DOE, LANL was founded in 1943 during biology and cell and tissue culture products Wond War II as part of the Manhattan to academic and industrial laboratories Project. Historically, the .defense-oriented involved in genetic and other basic biology national laboratories have focused on research. The company, headquartered In national security issues, but now their tech­ Gaithersburg, Maryland, has commercialized nical base is recognized for contributions in many enzymes and several modified nucleo­ other important complex technological tides and now develops an average of 400 areas. <> new products each year. Reported by Anne Adamson HGMIS,ORNL

Moore Calls Tech Transfer Critical to Future On January 24, W. Henson Moore, Depulv Secretary encourages the natural evolution of basic sci­ of Energy, spoke before the DOE Technology Transfer ence into precompetitive technologies, then ~If fundamental Seminar in Washington, D.C. Some of his remarks are into commercial systems, products, and jobs. research is the excerpted and summarized in the article below, starting pOint, DOE, one of six federal agencies that account he DOE science and technology mission, for almost all government R&D, has enor- technology trans­ Twhich encompasses fundamental research, mous resources to accomplish this mission. fer must be the !~?1ogy develop!,,~nt, and technology transfer, We have sonie 35,000 scientists and engineers, finish line." IS cntIcal ~o our nati

NIH Discusses cDNA Role with Invited Group

he NIH Human Genome Program physical maps that are complete or Temphasizes the construction of com­ nearly so. Studies of these genomes plete genetic and physical maps of the are at a point where cDNA research genomes of human and selected model could make a significant contribution organisms and development of new tech­ to understanding the biology of these nology and information systems to manage organisms, thereby increasing their mapping and sequencing data. Sequencing value as models for human studies. entire genomes will begin when the cost of sequencing is substantially below The group cautioned that this is a research current cost. area not previously envisioned as part of the 5-year goals. If cDNA studies are sup­ The NIH National Center for Human Genome ported, the group suggested the following Research (NCHGR) explored the usefulness considerations: of cDNA isolation and analysis in helping to achieve the Human Genome Project's 5-year • Long-term Human Genome Project goals. This examination comes in light of the goals should not be compromised for attention being given to cDNAs byhuman short-term payoffs. Full-scale pursuit genome programs in the United Kingdom, of cDNAs may result in dilution of effort some European countries, and more recently for quick biological returns. by DOE. A small group (see participants' list • Problems with current cDNA libraries below) that included members of the Program include structure and quality, correc­ Advisory Committee on the Human Genome tion for super abundance, achieve­ met December 2, 1990, in Bethesda, Mary­ ment of fUll-length cDNAs, detection land, to discuss the role cDNAs might play of alternate transcripts, and localiza­ in the NIH Human Genome Program. tion on the physical map. The group identified the following advan­ Participants suggested that NCHGR pursue tages of pursuing cDNA studies: development of technology with the follow­ ing objectives: • cDNAs are a source of sequence tagged site (STS) markers and can be • To identify all coding regions in a used to identify potential candidate large segment of genomic DNA. genes. • To construct and order high-quality, • A central goal of the Human Genome tissue-specific, full-length cDNA Project will be to identify stretches of libraries. DNA coding for proteins, and biolo­ gists would benefit more if they had The group also indicated that many cDNAs this information sooner rather than have been well characterized by biologists later. working in areas other than the Human Genome Project. They suggested that mech­ • Some model systems, such as Esche­ anisms be developed to facilitate identifica­ richia coli, Caenorhabditis e/egans, tion of STSs on these cDNAs and mapping and Drosophila me/anogaster, have of these cDNAs to chromosomes. The group recommended that NCHGR collaborate with other NIH components on this project. MEETING PARTICIPANTS (See announcement of RFA HG-91-02, David Cox Daniel Hartl Philip Sharp p.19. )0 University of Washington University Massachusetts Insti­ Reported by Bettie I. Graham, Chief California, School of Medicine tute of Technology NCHGR Research Grants Branch San Francisco ElkeJordan Edwin Southern Glen Evans NIH NCHGR University of Oxford Salk Institute for Robert Moyzis Sherman Weissman Biological Studies Los Alamos National Yale University Bettie Graham Laboratory Norton Zillder NIH NCHGR Maynard Olson Rockefeller University Mark Guyer Washington University NIH NCHGR School of Medicine Human Genome News, May 1991 9

NCHGR Advisory Council Holds First Session he National Advisory Council for Human Research (NCHGR) on the conduct of Next NCHGR TGenome Research held its first meeting in human genome research. training. and Advisory Council Bethesda. Maryland. on January 22. Council information dissemination related to the Meeting: June 7 members Qisted below) reviewed grants and Human Genome Project. were oriented on NIH procedures. The council also provides final review of The council advises the Director of NIH. the applications submitted to NCHGR for Secretary and the Assistant Secretary for research or training grants and coopera­ Health of the Department of Health and tive agreements and recommends Human Services. and the Director of the approval for projects that show promise. ¢ National Center for Human Genome ADVISORY COUNCIL MEMBERS: Francisco J. Ayala recent isolation of the cystic Fund; recipient of the Martin University of California, fibrosis and neurofibroma­ Luther King, Jr., Award. lTvine; population geneticist; tosis type 1 genes. Kay Jamison National Academy of Sciences Jerome R. Cox Johns Hopkins School of Medi­ member; Chairman of the Washington University; cine; clinical psychologist; Board of Basic Biology of the computer scientist with spe­ active with lay organizations National Research Council. cial knowledge in database that represent individuals with David Botstein management and design; con­ mental illness. Stanford University School of snltant and chair of numer­ Dorothy Nelkin Medicine; author of numerous ous computer science and New York University; interdisci­ scientific papers on genetics biomedical research boards plinary social scientist whose and molecular biology; mem­ and advisory committees. work has focused on the role ber of several editorial boards Norman Davidson of science in public policy and and advisory committees; California Institute of Tech­ on public understanding of sci­ member of the NIH Program nology; biologist; faculty mem­ ence; author of Selling Science: Advisory Committee on the ber since 1946; California How the Press Covers Science Human Genome, 1988--90. Scientist of the Year (1980). and Technology. K. Danner Clouser Joew.Gray Shirley M. Tilghman Pennsylvania State University Lawrence LivemlOre National Princeton University; molecular College of Medicine; philos­ Laboratory; biomedical scien­ biologist and developmental opher, educator. and bio­ tist; author of numerous pub­ geneticist; member of several medical ethicist; member of lications on flow cytometry advisory committees. numerous advisory boards; systems and cell cycles. Founding Fellow of The Keith R. Thmamoto Hastings Center. Hiliary H. Holloway University of California, New Atlantic Bank and coun­ San Francisco; biochemist and Francis S. Collins sel at the law firm of Marshall. biophysicist; National Acad­ University of Michigan and Dennehey, Wanzer, Coiemann, emy of Sciences member; Howard Hughes Medical and Goggin; memberofthe expert in gene organization, Institute; physician and molec­ National Board of Directors expression, and function. ular geneticist noted for the ofthe United Negro College NIH PACHG AppOints New Members, Chair tanford biochemist and molecular biologist Berg is currently Director of the Beckman S Paul Berg wOI succeed Norton D. Zinder Center for Molecular and Genetic Medicine (Rockefeller University) as Chair of the National in Palo Alto. California. and professor of Center for Human Genome Research biochemistry at Stanford University School (NCHGR) Program Advisory Committee on of Medicine. the Human Genome (PACHG). He will also Among his many honors are California Sci­ serve wnh Sheldon Wolff (University of Cali­ fornia) as Cochair of the DOE-NIH Joint Sub­ entist of the Year (1963). the Albert Lasker Basic Medical Research Award. the Nobel committee on the Human Genome. Berg and Paul Berg, Chair Prize in Chemistry. and the National Medal NCHGR Program two other new members. Diane Smith and Advisory Committee Robert Tjian. join PACHG for 4-year terms. (seePACHG,p.l0) on the Human Genome 10 Human Genome News, May 1991

DOE-NIH Establish Mouse Working Group For meeting minutes new joint working group has been • establish research priorities; or additional informa­ A established by the DOE-NIH Joint Sub­ tion on the DOE-NIH committee on the Human Genome to advise • identify research, training, and tech­ Mouse Working the committee on near-term and future nical needs; and Group, contact: research priorities and needs in mouse • coordinate U.S. research activities BeUie J. Graham, Chief genomic research as it relates to goals of with those of other countries, espe­ Research Grants Branch the Human Genome Project. All human cially Europe and Japan. NIH NCHGR genome joint working groups have the Bldg. 38A, Room 617 following general responsibilities: The 5-year plan states that the study of Bethesda, MD 20892 model organisms is essential to interpret­ 301/496-7531 • facilitate implementation of 5-year-plan ing data obtained in studies of humans and Fax: 301/480-2770 goals; to understanding human biology. For this reason, the plan continues, the Human DOE-NIH Mouse Working Group: Genome Project will support mapping and Verne Chapman William Dove Janet Rossant sequencing of the genomes of a select Roswell Park Cancer University of Mt. Sinai Hospital number of nonhuman organisms. The lab­ Institute Wisconsin, Madison Oliver Smithies oratory mouse is considered one of the most useful model organisms. Neal Copeland Joe Nadeau University of North NCI-Frederick Jackson Laboratory Carolina, Chapel Hill The mission and agenda of the NIH-DOE Cancer Research and Roger Reeves Richard Woychik Joint Working Group on the Mouse will be Development Center Johns Hopkins Oak Ridge National defined at its first meeting, scheduled for Frank Constantini University School of Laboratory May 6 in Bethesda, Maryland. The group Columbia University Medicine plans to meet twice yearly in the Washing­ ton area. <>

PACHG (from p. 9)

of Science. His memberships include the cellular biology to the committee, with a National Academy of Sciences, the Ameri­ specific focus in the field of virology and can Academy of Arts and Sciences, the Insti­ regulation of gene transcription. He has tute of Medicine, and the French Academy been an investigator at Howard Hughes of Sciences. Berg coauthored the recently Medical Institute since 1987 and professor published reference text Genes and in the Department of Biochemistry, Univer­ Genomes (see abstract, p. 18) sity of California, Berkeley, since 1982. His awards include the Pfizer Award for Enzy­ Diane C. Smith, who replaces outgoing com­ mology in 1983 and the Milken Family mittee member Jaime Carbonell (Carnegie­ Medical Foundation Cancer Research Mellon University), is an engineer and Award in 1988. mathematician who has been working in the field of computer science since 1972. After The 12 PACHG members are selected by serving on the computer science faculty at Department of Health and Human Services the University of Utah, she joined the Com­ (DHHS) Secretary Louis W. Sullivan. puter Corporation of America as Vice Presi­ PACHG gives advice on research directions dent for Advanced Information Technology. and goals of the Human Genome Project Smith is currently manager of technology to the DHHS Assistant Secretary for Health, r------'------, development for the Cus­ the NIH Director, and the NCHGR Director. To receive minutes of PACHG and tom Systems Division of See HGN 2(3),7 (September 1990) for a NIH-DOE Joint Subcommittee Meet­ the Xerox Corporation. ings, contact: complete list of PACHG members. <> Office of Communications Robert Tjian replaces NIH NCHGR David Botstein (Stanford Bldg. 38A, Room 617 University School of Bethesda, MD 20892 Medicine). Tjian brings 301/402-0911 broad experience in the Fax: 301/480-2770 areas of molecular and Human Genome News, May 1991 11

Workshop on Mouse Genome Mapping

he Fourth I nternational Workshop on Several crucial gaps in these maps are TMouse Genome Mapping, held November now being addressed. Strategies for iden­ 4--8, 1990, in Annapolis, Maryland, brought tifying centromeres and telomeres are together a community of scientists interested being developed, and new approaches for in mapping the mouse genome. The work of identifying polymorphic anonymous DNA chromosome committees began in Annapolis, segments should yield large numbers of and their reports are being prepared for pub­ widely distributed new markers. DNA vari­ lication in Mammalian Genome in 1991. ants associated with several telomeres have been identified, and a satellite probe, Workshop participants defined common specific for the centromeres of laboratory­ research goals for mapping the mouse strain mouse chromosomes, seems likely genome that reflect the unique strengths and value of the mouse as an experimental genetic system. These goals include development Mouse Chromosome Committees and dissemination of the following: CHROMOSOME CHAIR AND COCHAIRS • saturated genetic maps based on NUMBER well-spaced reference loci, 1 Michael Seldin, Duke University Medical School Beverly Paigen, Jackson Laboratory • physical maps of selected chromosome segments, and 2 Linda Siracusa, Thomas Jefferson University Catherine Abbott, University College, London • mouse genomics databases. 3 Miriam Meisler, University of Michigan, Ann Arbor • Genetic Mapping Michael Seldin, Duke University Medical School Goals: Establishment of about 160 to 320 4 Jeffrey Friedman, Rockefeller University reference loci spaced 5 to 10 cM apart on Konrad Huppi, NIH National Cancer Institute (NCI) each chromosome. Ideal reference loci 5 Christine Kozak, NIH National Institute of Allergy and have the following characteristics: Infectious Diseases Dennis Stephenson, Roswell Park Cancer Institute • inexpensive and easy to type, 6 Rosemary Elliott, Roswell Park Cancer Institute • highly variable among laboratory Nathan Bahary, Rockefeller University strains as well as diverse Mus species, 7 Eugene Rinchik, Oak Ridge National Laboratory • universally available as markers typed Steve Brown, St. Mary's Hospital Medical School, London by polymerase chain reaction (peR) 8 Jeffrey Ced, Frederick Cancer Research and Development assays as well as Southern blotting, Center, NCI • derived from expressed genes, and Jo Peters, Medical Research Council • conserved between humans and mice. 9 David Kingsley, Frederick Cancer Research and Development Such sets of reference loci will provide uni­ Center, NCI versal cross-reference points for mapping 10 Ben Taylor, Jackson Laboratory specific genes of interest and a framework Monica Justice, Frederick Cancer Research and Development for high-resol ution mapping of specific Center, NCI chromosomal regions. 11 Arthur Buchberg, Thomas Jefferson University Sally Camper, University of Michigan, Ann Arbor Results: Unambiguously ordered multilocus 12 Peter D'Eustachio, New York University Medical Center maps of extended linkage groups, with adja­ cent markers spaced no more than 20 eM 13 Monica Justice, Frederick Cancer Research and Development apart, for aI/ chromosomes. The maps are Center, NCI Dennis Stephenson, Roswell Park Cancer Institute composed largely of named genes identified by recombinant DNA probes in Southern 14 Joseph Nadean, Jackson Laboratory blotting assays. Hundreds of genes are 15 Beverly Mock, NIH National Cancer Institute being placed each year. Saturated maps 16 Roger Reeves, Johns Hopkins School of Medicine now exist for most segments of the X chro­ Muriel Davisson, Jackson Laboratory mosome, estimated to be 80 cM in length; 17 Lee Silver, Princeton University over 50 ordered DNA markers are spaced 18 Muriel Davisson, Jackson Laboratory no more than 5 cM apart. Extended regions 19 Jean-Louis Guenet, Institut Pasteur of chromosomes 1, 2, 3, 16, and 17 are X Steve Brown, St. Mary's Hospital Medical School, London similarly well mapped. Physical mapping Philip Avoer, Institut Pasteur studies have already confirmed the accuracy of some maps. Y Eva Eicher, Jackson Laboratory 12 Human Genome News, May 1991

to provide a genetic tag for centro­ development and in neural function. These Copies of the workshop meres as genetic loci in interspecies deletion resources will be useful in the long­ program and abstracts are backcrosses. range physical mapping of several regions available from: of the mouse genome. Novel uses of oligonucleotides as Verne Chapman Department of Molecular probes or as PCR primers have dra­ • Databases and Cellular Biology matically increased the number of Goals: Collection, integration, analysis, Roswell Park Cancer Institute polymorphic loci available while reduc­ display, and dissemination of mouse Elm and Carlton Streets Ing the time and genomic DNA con- genomic information. Buffalo, NY 14263 sumed in doing the assays. Some 716/845-5840 combination of strategies seems likely Results: An impressive collection of data­ Fax: 716/845-8169 to provide the markers needed to fill bases recording gene mapping results, the remaining gaps in the genetic map. molecular clones and probes, and physi­ Other strategies exploit cross hybridization cal mapping data. Specific modifications of mouse genomic DNA with human variable were discussed to ensure that each data­ number tandem repeat probes and with ran­ base can continue to accommodate data domly chosen oligomer sequences. Other flow and store increasing amounts of raw methods appear likely to define numerous data (e.g., recombination fractions and useful polymorphisms throughout the haplotypes) as well as derived interpreta­ mouse genome. tions (e.g., linkage maps). Work is under way to create methods for integrating and Elegant in situ hybridization experiments displaying these data in interactive systems suggest that many repeated sequence that draw simultaneously on several data classes that are widely distributed over the sources. Also, efforts are being made in genome may tend to concentrate in regions conjunction with the Genome Data Base corresponding to Giemsa bands. This biased project to provide users with ready access distribution raises the intriguing possibility to integrated mouse and human genomic that in the course of pushing genetic maps information. to closure, much will be learned about the physical organization of mammalian chro­ • Conclusion mosomes and perhaps about the evolution Elaboration of a mouse genome map of the organization as well. based on DNA markers is well under way. • Physical Mapping Based on visible mutations and biochemi­ cal markers, numerous points of cross Goals: Physical analysis of regions of partic­ reference to the classical map have been . ular genetic interest, with the long-term goal established. The use of several mouse of an ordered set of recombinant clones species and genetically defined inbred spanning the whole genome. strains has yielded highly informative Results: Availability of physical maps span­ genetic mapping resources that have ning megabase regions near loci of interest. been especially valuable in mapping These data, together with the growing num­ functional genes. ber of yeast artHicial chromosome (yAC) Thus, the usefulness of comparing mouse clones centered on genes of interest, sug­ with human genetic and physical maps gest that resources already available for has increased as more mouse genes have large-scale cloning and mapping may be suf­ been mapped and as experimental models fiCient to assemble large parts of the desired of human hereditary disease have been long-range DNA map of the mouse genome. identified. The ability to define, map, and Use of YACs to attack genomic regions of manipulate mouse genes makes the special interest is rapidly becoming routine. species a unique laboratory resource for Simultaneously, significant technology devel­ studying the genetics of biologically and opment is taking place. Improved methods medically important traits. 0 were reviewed for screening high-denstty Reported by Verne Chapman filters of YAC libraries and for generating Roswell Park Cancer Institute, and Interpreting fingerprinting data for YAC Peter D'Eustachio clones. New York University Medical Center, and A particular advantage of using'the mouse Joseph Nadeau as an experimental system Is a series of Jackson Laboratory deletion mutations centered on several genes known to play crucial roles in eariy Human Genome News, May 1991 13

Second X Chromosome Workshop he second X Chromosome Workshop, The chromosome was divided into Tfunded by the U.K. Medical Research intervals by well-characterized X Chromosome contact: Council, was held at St. Catherine's College, somatic cell hybrid breakpoints, Kay Davies Oxford, on January 5-7. Some 70 participants which may be used as common Molecular Genetics Group heard short presentations of new mapping reference points on the map [Peter Institute of Molecular Medicine data and then divided into four groups to con­ Goodfellow (ICRF); Willard]. Most Jobn Radcliffe Hospital struct physical and genetic maps and to com­ chromosome regions are being Headington, Oxford 0X3 9DU pile a table. The table indicates where contigs actively mapped both genetically United Kingdom are available and which laboratories have yeast and physically because a disease artnicial chromosome \fAC) clones of interest. 10cLis of interest exists in most intervals. Reference marker Copies of the table, which has been submitted positions based on the The Genome Data Base [Peter Pearson to Genomics, are available on request from X-chromosome com· (Johns Hopkins University)] was accessible Kay Davies (see box, upper right). A sum­ mittee report from mary of the reference markers is presented during the meeting so participants could HGMIO.5 (Oxford) input data and reference the database. and modified to include in the figure at lower right. information presented The third X Chromosome Workshop, to be Although a complete genetic map of the X chro­ at tbe workshop, This organized by Daniela Toniolo (Consiglio mosome has been available for some time, it information concerns was based largely on markers with restricted Nazionale delle Richerche) and Michele physical ordering and D'Urso, will be held in Italy in 1992. <> map positions for the information potential. Several microsatelltte Xpter region together markers along the chromosome now indi­ Reported by Kay Davies Institute of Molecular Medicine with the order of cate that a higher-resolution map will soon and markers around the be available; 12 Mb of the short-arm telomere Ian Craig putative inactivation have been mapped by pulsed-field electro­ University of Oxford center and the fragile phoresis [Christine Pettt (Institut Pasteur); site (contributors Andrea Ballabio (Instituto G. Gaslini)]. and an acknowledged in text). equivalent map has been constructed for the X CHROMOSOME Xpter Consensus Order long-arm telomere [Anne-Marie Poutska (Ger­ REFERENCE MARKERS and Distances man Cancer Research Center); Hans Lehrach DXYS14 0.01 Mb (Imperial Cancer Research Fund {ICRF})]. 22.3 Researchers are currently assembling YAC 22.2 DXS16 P DXYS60 0.30 Mb contigs to complement these studies. 22.1 DXS41 DXYS15 0.85 Mb Important contributions were made to the 21.3 DXS28 21.2 DXS164 characterization of sequences expressed 21.1 ( DXS84 PABX 2.70 Mb OTe from inactive X chromosomes and mapped 11.4 DXS7 STS 7.40 Mb in the region containing the putative inacti­ 11.3 11.23 OXS426 vation center [Ballabio; Huntington Willard 11.22 OXS255 DXS143 9.40 Mb 11.21 (Stanford Universtty School of Medicine); 11.1 11.1 DXZl Philip Avner (Institut Pasteur)]. Methylation 11.2 12 DXS1S9 differences close to the fragile site in individ-' AR Order of Markers 13 PHKA Around Putative uals expressing the phenotype were separ­ RpS4"X Inactivation ately reported by the laboratories of Jean­ XISt Centre (xis!) 21.1 DXS72 PGKI Louis Mandel (Institute National de la Sante 21.2 et de la Recherche Medicale) and Davies. DXYSIX 21.3 DXS3

Mapping resources for the X chromosome DXS17 were disG:ussed. Several groups are screen­ ing YAC libraries to complete a contig map q

of the chromosome [Thomas Caskey (Baylor DXS42 College of Medicine); Centre d'Etude du HPRT Polymorphisme Humain; Lehrach; Robert DXSSl Nussbaum (Universtty of Pennsylvania DXS463 School of Medicine); David Schlessinger ( DXS105 DXS477 Order of Markers DXS369 (FRAXA) Around Fragile F9~ DXS46S' (WaShington Universtty School of Medicine); Site ( DXS304 DXS533' Michele D'Urso (internationalinstttute of DXS52 OXS296 Genetics and Biophysics)]. Ordered cosmid libraries are proving a valuable resource 'Probes for these loci detect (by PFGE) methylation diHerences in males expressing the fragile site [Lehrach; David Bentley (Guy's Hospttal)]. at Xq27.3 (see text) 14 Human Genome News, May 1991

Nonprofit Resource Centers Facilitate Mapping Researchers nvestigators in the international Human • 1005 protozoan type cultures, Genome Project and others often rely on Can Readily I • 1485 animal and plant viruses, and Compare centralized sources of cell lines and DNA Results Obtained to facilitate mapping. For nominal fees, • over 3000 human and other animal these nonprofit sources offer reliable, well­ cell cultures. with Well­ characterized cell cultures and DNA samples Characterized that enable comparison of results from dif­ ATCC recently added a collection of recom­ Cell Cultures and ferent laboratories. In addition, individual binant DNA probes, clones, and libraries; DNA Samples laboratories are spared costly and time­ approximately 400 new probes and 5 to consuming storage and distribution and are 10 new libraries will be added annually. given access to the latest resources. A description of several useful ATCC map­ ping resources follows. Repository services include collection, authen­ tication, amplification, storage, and distribution DNA Probes and Libraries Repository of cells and DNA, including management of In 1985 the NIH National Institute of Child updated information on all holdings. Several Health and Human Development (NICHD) repositories also maintain databases on resutts established an international Repository obtained using their resources. Access to of Human and Mouse DNA Probes and some of the resources may be limited. Libraries within ATCC. Repository functions include the following activhies: U.S. CENTERS 1. DNA Probes; Clone and Genomic Two major U.S. resource centers are the Collections. Repository staff obtain, American Type Culture Collection (ATCC) amplify, and distribute over 100 probes in Rockville, Maryland, and the Corieilinsti­ detecting restriction fragment length poly­ tute for Medical Research in Camden, New morphisms (RFLPs). They also maintain Jersey. ATCC, a private, nonproftt organiza­ clone and genomic repositories from known tion, maintains the most diverse existing genes independent of RFLP detection. collection of microorganisms and cell lines, including bacteria, fungi, protozoa, viruses, • The clone repository - over 1640 metazoan cell lines, and DNA recombinants. human and 155 mouse clones­ Coriell houses the world's largest collection contains discrete sequences distrib­ of human cells and offers somatic cell hybrid uted throughout the human and resources. mouse genomes. Clones spec~ic to each human chromosome and most Other important resource facilities Include mouse chromosomes are available. the National Cell Culture Center and the Restriction analysis is used to verify Jackson laboratory. The newly established the structure of all clones received. National Cell Culture Center in Minneapolis, A photograph of the ATCC restriction Minnesota, provides large-scale mammalian digest gel and a sample of the ATCC ~ ______L.~ cell culture services. Jackson lab- clone preparation are returned to the ATCC Catalogue oratory, located in Bar Harbor, Maine, depositor for confirmation before the The fourth edition of the offers mouse strains, mutations, and clone is distributed as transformed ATCC/NIH Repository Cata­ mouse DNA resources. bacteria or bacteriophage. Clones with logue of Human and Mouse These centers are under contract to human inserts may also be available DNA Probes and Libraries various federal agencies to provide as purified DNA. The NICHD contract (1990) lists materials depos­ resources to or serve as repositories mandates that 300 human and 100 ited at ATCC as part of the for the research community. mouse clones be added annually. DNA repository. Also enu­ merated are related materials • The genomiC repository was estab­ from the ATCC molecular .ATCC lished in 1988 to maintain a collection biology collection and Patent Since 1925 ATCC has maintained and of clones constttuting a complete Culture Depository. distributed biological resource material genome .. Its primary function is to Contact for catalogue: to the intemational research communhy: develop and evaluate methods and 800/638-6597 or 301/881-2600 It offers the following tradhional material: instrumentation needed to maintain a human genome reposttory. These Fax: 301/321-5826 • 13,630 bacterial strains, Repository information: methods include automated DNA Donna Maglott, 301/231-5586 • 24,780 strains of filamentous preparation; clone verHication; data Fax: 3011770-1541 fungi and yeasts, maintenance and analysis; and Human Genome News, May 1991 15

sample storage, recovery, and distribu­ • Aging Cell Repository of the National tion. Currently available are 850 clones Institute on Aging, created in 1974; ATCC Repository from the Saccharomyces cerevisiae and Database Access genome (provided by Maynard Olson's Use of the menus • National Cell Repository (NCR) of the Washington University Laboratory), requires emulation National Institute of Mental Health. organized in about 180 different contigs. of a VT100 terminal Established in 1990, NCR facilttates (8 data bits, a stop 2. National Laboratory Gene Library research on the genetic components bit, full duplex, parity Project (NLGLP) Resources. Sixty of manic depression, Alzheimer's dis­ none) and a 1200- chromosome-specific gene libraries con­ ease, and schizophrenia. This reposi­ baud modem. Log on structed at Lawrence Livermore filational tory is expected to add 6000 cell lines is automatic after Laboratory (LLNL) and Los Alamos National by 1993 and to achieve a total of calling 301/881-4909 Laboratory (LANL) are preserved and 7500 additional lines by 1995. and answering the distributed by ATCC. [HGN 2(1), 12-13 prompts with the The three repositories above, in addition to (May 1990)). word "common" smaller collections on cancer, diabetes, followed by return{ 3. Information Management/Database. and other diseases, are collectively known enter. Telephone Catalogues, information sheets, and a menu­ as the John T. Dorrance, Jr., International service is the only driven online database describe the reposi­ Cell Science Center. Richard Mulivor is the charge. tory's holdings. For information on database director. access, see box at right. Cell Lines. All cell lines, which are derived 4. DNA Primers. ATCC offers predesigned from samples collected worldwide, are oligonucleotide primers for in vitro amplifica­ screened to confirm species of origin and tion of human DNA, including oligonucleo­ for mycoplasmas and other contaminants, tide pairs for 50 polymorphic loci. Product are well characterized, and are clinically sheets give information on primers, including documented. An extensive bibliographic allele sizes, gene name, cytogenetic location, database and abstracts of Itterature cttations and sequence. documenting culture characterizations are also maintained. Other ATCC Mapping Resources Human Cultures. Coriell maintains cell Coriell Houses ATCC offers over 3000 well-characterized cultures (derived from human fibroblasts, World's Largest cell lines and hybridomas through five dif­ Iymphoblasts, and amniotic fluid) that rep­ Human Cell ferent government-sponsored collections, resent over 400 genetic diseases and 800 Collection thus providing a valuable resource for study­ chromosomal aberrations. Virus-transformed ing gene expression. About 80 species are fibroblast cultures and cultures from appar­ represented, with the majortty of cultures ently normal individuals are also available. being human, lower primate, or laboratory animal in origin. [Contact: Technical Collec­ To aid linkage analysis studies, Coriell offers tion Specialist, 301/231-5553.1 cultures from multigenerational family groups; databases are being maintained by several contributors of samples. Within • Coriell Institute for Medical the collections are samples from affected Research individuals and families (including non­ affected members) with cystic fibrosis, Located on the campus of the University of Medicine and Dentistry of New Jersey, the fragile X-linked mental retardation, Hunting­ Coriell Institute is a nonprofit biomedical ton's disease (from the Venezuelan pedi­ gree), retinitis pigmentosa, and major research instttute that establishes, charac­ affective disorder (from the Amish pedi­ terizes, stores, and distributes over 7000 gree). Utah pedigrees were contributed by cell lines worldwide. Coriell has provided cells to scientists around the world for Ray White and collaborators at the Howard 18 years and in 1990 began offering DNA Hughes Medical Institute (HHMI) in Utah. samples. Somatic Cell Hybrids: Cultures and DNA. Human/rodent somatic cell hybrids Three major NIH cell repositories housed at are available as cultures and purified DNA. Coriell compose the world's largest collec­ tion of human cells: For details on their mapping panel, see box, p. 16. Coriell also offers DNA from • Human Genetic Mutant Cell Reposttory monochromosomal hybrids for human of the National Institute of General Medi­ chromosomes 2-9, 11-14, 16-19, 21,22, cal Sciences, founded in 1972; X, and Y, as well as DNA from hybrids 16 Humau Genome News, May 1991

retaining 3 or fewer human chromosomes in Sponsored by NIH National Center for a variety of combinations. Research Resources, this service is avail­ able to researchers throughout the United [Contact for Coriell collections: Richard States and Canada. The Scientific Advisory Mulivor, 6091757-9697. Catalogue: 800/752- Committee selects and prioritizes requests; 3805 or 6091757-4848, Fax: 609/964-{)254.] preference is given to NIH-supported proj­ ects. Researchers are charged only for con­ • National Cell Culture Center sumable materials and a portion of labor The National Cell Culture Center offers cus­ costs for each project. [Application form or tomized services for large-quantity produc­ additional information: Mark Hirschel, direc­ tion of animal cells and secreted proteins. tor, 800/325-1112, Fax: 6121786-{)915.] By providing access to state-of-the-art cell culture instrumentation and techniques, this • Jackson Laboratory Located in Bar Harbor, Maine, Jackson Laboratory maintains a widely diverse col­ The National Cell Culture Center lection of genetically defined mice for basic addresses needs ofsmall research research and for studies of genetic and laboratories as well as those developmental factors underlying a variety of larger efforts. of disorders. Over 700 different mutations and 1000 different strains and sets of recombinant inbred strains and congenic new program addresses the needs of the strains are regularly used for mapping small research laboratory as well as those of studies by scientists worldwide. These are larger collaborative groups. The center pro­ available through the laboratory's Founda­ vides cells in suspension and monolayer cul­ tion and Special Mouse Stocks, Mouse tures in quantities ranging from 25 to 150 L. Mutant Resource, and Robertsonian In addition, cell-secreted products such as Chromosome Resource. monoclonal antibodies are available in quan­ tities of 1 to 100 g. The Mouse DNA Resource offers genomic DNA (from splenic extracts) from inbred, congenic, and mutant-bearing mouse strains. [Contact: Marie Ivey, 207/288-3371, Human/Rodent Somatic Cell Hybrid ext. 1395.] Mapping Panel Available from Coriell The Genetic Information Resource compiles The National Institute of General Medical Sciences (NIGMS) Human and distributes information on the labora­ Genetic Mutant Cell Repository has Mapping Panel No.1 DNA samples tory's numerous mouse strains and mutants available for distribution. The panel consists of DNA isolated from 18 (e.g., genetic linkage data that can be visual­ human/rodent somatic cell hybrids retaining from 1 to 19 human chromosomes. Fifteen samples were isolated from human/mouse ized directly or on chromosome maps), spe­ somatic cell hybrids resulting from the fusion of male human fibro­ cific gene typing for given strains, literature blasts (IMR-91) with the thymidine kinase-deficient mouse cell line references, and phenotypic characteristics (B-82). The panel is completed with DNA isolated from three mono­ of strains. In addition, the GBASE database chromosomal hybrids retaining human chromosomes 9, 16, and X. maintains information about mouse loci, allelic characterization of inbred strains, and The panel has been characterized by the following: genetic maps. • G-banded chromosome analysis; • in situ hybridizatiou analysis using biotinylated total human DNA to detect human chromosomes, human/rodent translocated chromo­ INTERNATIONAL CENTERS somes, and human chromosome fragments; and • Southern blot hybridization. • U.K. DNA Probe Bank Probes were used for the short and long arms of all human chromo­ Funded by the Medical Research Council somes except 10, 13, 14, 15, 20, and 21, all of which were analyzed as part of the U.K. Human Genome Map­ with long-arm probes only. The panel consists of 50 f1g of DNA from ping Project Resource Centre, the probe each hybrid and 100 f1g of DNA from each of three parental human bank offers some 650 DNA probes free to and rodent cell lines. the U.K. research community. Foreign Contact: Human Genetic Mutant Cell Repository; Coriell Institute investigators may be subject to fees and for Medical Research; 401 Haddon Avenue; Camden, NJ 08103; restricted access [HGN 2(6), 1-3 (March [8001752-3805 in the United States; 6091757-4848 from other 1991)]. [Contact: Christine Bates, (In!.) countries; Fax: 6091964-0254}. 44/81-869-3446, Fax: (Int.) 44/81-869-3807.] Human Genome News, May 1991 17

• European Cell Bank moved to the CEPH public database (avail­ DNA and Cell The European Cell Bank consists of two com­ able to the general scientific community). Repository ponents serving gene mappers in the United Unpublished data can be released to the Services: Kingdom and Europe: public database after 2 years. [To receive the database, available on a 5.25-in. disk, • collection • European Collection of Animal Cell Cul­ and a book of LOD scores and recombina­ • authentication tures Human Cell Bank, housed at the tion-frequency estimates for syntenic Public Hea~h Laboratory Service (PHLS) markers in the database, write to CEPH; 27 • storage at Porton (United Kingdom), prepares rue Juliette Dodu; 75010 Paris, France.] and distributes Iymphoblastoid and • distribution other cell lines. Many lines have consti­ Consortium Linkage Maps. CEPH inves­ tutional chromosomal rearrangements tigators construct consortium maps of with breakpoints useful for human gene each chromosome, using published data mapping. Foreign investigators may from the database. The first such map, of have restricted access to some materials. chromosome 10, was recently published [Contact: B. Bolton, PHLS Centre for [Genomics 6, 393-412 (1990)] with a Applied Microbiology and Research, mean distance of 11 cM between genetic (Int.) 44/0980-610391, Fax: (Int.) markers. The second consortium map, of 44/0980-611315.] chromosome 1, was published in April [Genomics 9, 686-700 (1991)] with a • Department of Cell Biology and Genetics mean genetic distance of 6.7 cM. To pro­ at Erasmus University (Rotterdam) vide resources for constructing higher­ banks fibroblast lines, with particular resolution maps (perhaps 1 to 2 cM), emphasis on inbom errors of metabolism. CEPH is enlarging its reference panel to [Contact: V. Cleijer, (Int.) 31/10-408- include 61 families. 7223, Fax: (Int.) 31/10-408-7200.] Probe Collections. A project being devel­ oped in collaboration with ATCC is the • Centre d'Etude du Polymor- construction of probe kits for the mapped CEPH phisme Humain (CEPH) genetic markers on CEPH consortium maps. Coordinates Sponsored by NIH National Center for Collaborators' The mission of CEPH, established in Paris in Research Resources, this project aims to 1983 as a nonprofit institution, is to facilitate enhance the use of the CEPH consortium Gene Mapping construction of human genetic linkage maps genetic linkage map by enabling researchers Using Its Family of each chromosome by using DNA poly­ to localize disease-determining and other Reference Panel morphisms. CEPH coordinates international interesting genes. gene-mapping efforts for collaborating [Contact for CEPH: Howard Cann, Fax: researchers in laboratories in North America, (Int.) 33/1-40-18.Q1-55 (Paris).] Europe, South Africa, Japan, and Australia. Reference Panel. The main premise of • Japanese Cancer Research CEPH is that collaborative research on DNA from the same families will result in earlier Resources Bank completion of the human genetic linkage The Japanese Cancer Research Resources map. CEPH provides its collaborators with Bank, established to facilitate cancer free, high-quality cellular DNA samples from research, includes cell and gene reposi­ a panel consisting of DNA from 40 large tories. Resources are available to qualified families (each with at least 6 children) with no investigators associated with certain medi­ known genetic diseases. Collaborators use cal, research, or educational organizations. their own probe and restriction enzyme com­ [Contact: Katsuyuki Hashimoto; Gene binations to determine the genotypes of Repository Section; National Institute of various DNA polymorphisms for the entire Health; 10-35, Kamiosaki 2-Chome; Shina­ panel. All data are sent to the CEPH database. gawa-ku, Tokyo 141; (Int.) 81/03-444-2181, Database. The CEPH database, containing ext. 304, Fax: (Int.) 81/03-446-6286.] <> genotypes for all tested genetic markers Reported by Denise Casey (mostly DNA polymorphisms), consists of a HGMIS,ORNL collaborative portion and a public portion. The collaborative database, available only to CEPH investigators, includes unpublished and published data. Published data are later 18 Human Genome News, May 1991

JoIuman Genome Genome Literature Abstracts news fTAs time and space permit, Human DNA Science: A First Course in Recombi­ II Genome News will publish information nant DNA Technology by David A. Micklos . 11111111111111111111 about selected new books and journals that (Cold Spring Harbor Laboratory) and Greg may be of interest to our readers. This is not a A. Freyer (Columbia University) is a labora­ comprehensive list, and announcements will tory text !hat. introduces the theory, practice, be taken from material at hand. We welcome and applIcatmns of recombinant DNA tech­ news from authors and publishers about new nology. Written in a semijournalistic style and National Center designed to be read from cover to cover the > ' systems that have been especially illuminated by the recombinant DNA approach. Over 700 illustrations are included. Casebound with ja<;ket, $52. [Marketing D.irector, University SClence Books; 20 Edgehill Road; Mill Valley CA 94941.] , Human Genome News, May 1991 19

New Technologies To Detect U.S. Genome Research Funding Information All Genes and Coding Note: Investigators wishing to apply for NIH funding are urged to Regions in Genomic DNA discuss their projects with agency staff before subruitting formal I proposals. DOE requires no prior discussion on preproposals . • RFA HG-91-02 The National Center for Human Genome Research invites applications for research NIH National Center for Human Genome Research grants to support the development of either Application receipt dates: of the following: • ROI, POI, R21, P30, P50, and RI3 grants - February 1, June 1. • new techuologies or research strategies and October I . capable of detecting all coding sequences and/or genes in genomic DNA; or • Individual postdoctoral fellowships and institutional training grants - January 10, May 10, and September 10. o more general and efficient methods of preparing, isolating, and characterizing • Small Business Innovation Research Grants (SBIR: firms with libraries of intact cDNAs. 500 or fewer employees) - April 15, August 15, and December 15. Project emphasis will be on experimental rather o Requests for Applications (RFAs) - receipt dates are indepen­ than computational approaches. dent of the above dates (see notices at left and on next page). Timetable Program announcements are listed in issues of the weekly NIH oLetter ofIntent receipt (recommended but Guide for Grallts alld COlltracts, which may be obtained by: not required for apphcation): June 17. - Hard copy subscription - ca11301/496-7441. oApplication receipt: July 15. - Remote log in via modem to NIH Grant Line - call John James, 301/496-7554. • Initial Review Group review: February 1992. - Listserver computer network subscription­ • Earliest funding: April 1992. call Dottie Baker, 9191966-5625; For more information or a complete copy of BITNET: "[email protected]" or the RFA, contact: Bettie J. Graham, Chief; Internet: "[email protected]" Research Grants Branch; NIH NCHGR; Expanded statements of RFAs listed in the NIH grants Building 38A, Room 612; Bethesda, MD 20892; guide may be obtained from either of the two electronic 301/496-7531; BITNET: "[email protected]"; sources or from NIH NCHGR in Bethesda, MD Internet: "[email protected]" <> (301/4%-0844).

Human Genome Program DOE Human Genome Program Developmental Grants (P20) Solicitations for proposals were published in the February 20 issue of the Federal Register, in the February 22 issue of Science, and in • RFA HG-91-04 other publications. Investigators whose preproposals are accepted The National Center for Human Genome for programmatic relevance are notified to submit a formal proposal Research announces the availability of nonrenew­ due August 9. Further information can be obtained via: able developmental grants (P20) to provide sup­ Internet: "[email protected]" port to groups of outstanding investigators who wish to undertake the following: SBIR Grants. DOE also invttes small business firms to submit grant applications addressing the human genome topic of SBIR pro­ o develop interdisciplinary research collabora­ grams, which are designed to strengthen innovative firms in areas tions and strategies, of research and development and to contribute to the growth and o obtain preliminary results that demonstrate strength of the nation's economy. The human genome topicempha­ feasibility, and sizes instrumentation development for automated clone processing. o develop a research plan addressing a major improvements in DNA sequencing technologies, and enhanced research goal of the Human Genome Project. sequence data storage and processing capabilities. The plan would be used as the application basis Selected firms may receive up to $50,000 to explore the feasibility for a program project (POI) or center grant (PSO). of their ideas. In a second phase, up to $500,000 will be available TImetable to individual firms to support those ideas judged highest in potential • Letter of Intent receipt: May 9 and for meeting program objectives. For more information, contact: September 14. Samuel Barish; SBIR Program Manager, ER-16; DOE; Washington, oApplication receipt: July 9 and November 14. DC 20585; 301/353-5707. Next submission date: spring 1992. To obtain the full RFA and instructions, contact: Human Genome Distinguished Postdoctoral Fellowships. Jane L. Peterson, Chief, Research Centers Next deadline: February 1, 1992. For further information, see HGN Branch; NIH NCHGR; Building 38A, 2(3), (September 1990) or contact: Room Bethesda, MD 20892; 301/4%-7531, Oak Ridge Associated Universities: 6151576-4805 <> Internet: <> 20 Human Genome News, May 1991

Studies of Testing, Counseling for Cystic Fibrosis Mutations

• RFA HG-91-01 Appropriate topics include education before Assistance awards are available for studies of testing, counseling after testing, optimum test the clinical delivery of individual and family settings, levels of understanding and interest educational and counseling services related to among different populations, recordkeeping DNA-based testing for the genetic mutations and disclosure policies, and test accuracy and that cause cystic fibrosis. The following NIH cost-effectiveness. institutions invite applications: TImetable .National Center for Human Genome oLetter ofInlent receipt (recommended but Research (NCHGR), not required for applIcation): May 1. • National Institute of Child Health and .Application receipt: June 7 . Human Development, • Initial and council reviews: July-September. • National Center for Nursing Research, and • Earliest award: September 30. o National Institute for Diabetes and Diges- For additional information or a copy of the tive and Kidney Diseases. complete RFA, contact: This RFA is intended to solicit research Eric T. Juengst, Director; Ethical, Legal, and projects that can be used to identify clinical Social Implications Program; NIH NCHGR; practices that best increase patient under­ Building 38A, Room 614; Bethesda, MD 20892; standing of disease-gene carrier testing and 3Olj4%-7531; Internet: "[email protected]" 0 test results. Practices should also protect indi­ viduals and families from test-related psycholog­ ical harm, stigmatization, and discrimination.

Genome-Related Tutorials Offered

Mathematical Sciences Ethical Implications he Societal Institute of the Mathematical "Genomic Information: Ethicallmplica­ TSciences (SIMS) will conduct a tutorial tions," an intensive, advanced-level course, on the mathematical sciences in genomic will be held November 4--8 at the University analysis on August 4--24 at Stanford Univer­ of Washington, Seattle. Partly sponsored by sny' Participants will explore how quantita­ the National Center for Human Genome tive methodologies can be used effectively Research, the course will include an intro­ in genomic analysis, particularly in connec­ duction to relevant methods and issues in tion wnh the Human Genome Project. Topics bioethics for scientists and an introduction will include fragment assembly, informatics, to the scientific and clinical features of the pattern analysis of molecular sequences, genome project for bioethics/humanities and DNA and protein structure predictions. scholars. The workshop aims to promote Several days of background lectures will discussion and sound analysis of the ethical prepare participants for the later presenta­ and social issues that will arise from data tions of senior tutorial faculty. produced in the genome project. The tutorial is supported by a grant from Fifteen participants from each discipline the National Center for Human Genome will be selected. Women and minorities are Research. Funds are available to qualified especially encouraged to apply, and two participants for travel and living expenses fee waivers are available. Applications are while at Stanford. The tutorial will be held due July 19. This workshop will also be again in the summer of 1992 on the East offered June 15-19,1992. 0 Coast. 0 Contact: Contact: Inge Boulanger Societal Institute or the Mathematical Department or Medical History and Sciences Ethics, SB-20 97 Parish Road South University or Washington School or New Canaan, CT 06840 Medicine 203/966-1008 Seattle, WA 98195 Fax: 203/972-6069 206/543-5447 Human Genome News, May 1991 21

S~nk~~;~:,~on the Human Genome Project at the 82nd Annual Meeting of 15-18 tl Association for Cancer Research; Houston, TX Fax: 215/440-9313) Research in Psychiatry" at the May 16 Annual Meeting; Orleans, LA

*Second International Chromosome 11 Physical Mapping Workshop; Paris [0. Evans (US.), Fax: 619/558-9513 or e. funien (Int.) 33/1-42-24-1357) C. elegans Meeting; Madison, WI 608/262-2755; Other information: P. Anderson, 608/263-8429) Genome Research in an Interdependent World; Bethesda, MD [D. Wikler, 608/263-6287) · "National Advisory Council for Human Genome Research; Bethesda, MD Genetic Testing; Berkeley Springs, WV

·NIH Program Advisory Committee on the Human Genome; MD · [e. Mohan, 301/496-0844, afternoolls) · Joint NIH-DOE Subcommittee on the Human Genome; Bethesda, MD [see cOlltact: fUlle 25) Bethesda, MD }XXt1""D1cal and Pastoral Care Issues in Genetics; Washington, DC [F. Seydel, 202/687-8810) I manu of Dimes Clinical Genetic Conference: Developmental and Genetic 7-10 Disorders of the Central Nervous System; Vaocouver, BC [March of Dimes Birth Defects Foundation, 914/428-7100) ~'Social Issues in Human Genome Research" symposium at the International 13 Society for the History, Philosophy, and Social Studies of Biology Conference; Evanston, IL [P. Stewart, 703/231-7687, Fax: 703/231-9307) ·Workshop at AAAI-91 Conference: AI Approaches to Classification and Pattern Recognition in Molecular Biology; Anaheim, CA July 14-19 [M. Noordewier, "'High Performance Cdmputing in Biology and Medicine" and "Computa­ tional Molecular Biology and Genetics" at the 13th IMACS World Congress 22-26 on Computation and Applied Mathematics; Dublin [M. Wittell, USA, 512/471-2472, Fax: 512/471-2445, E-mail: "[email protected]" or ''xxvb [email protected] ") Research Conference on Molecular Genetics; Newport, RI 29-Aug.2 (A. Cruickshank, 401/783-4011, Fax: 401/783-7644) Conference; Interlaken, (lilt.) 41/1-724-8645, 11th International Workshop on Human Gene Mapping (HGM 11); London [f. Crowther, (Int.) 44/71-269-3389, Fax: ([lit.) 44/71-430-1787) Bacteria and Phages; CSHL, Cold Spring Harbor, NY abstract deadline: June 11 [CSHL, 516/367-8346,

York, 1-6

September 10-13 Human Genome Project: A Public Forum; Alexandria, VA 14-15 800/336-GENE or 202/331-0942) • Attendance at meetings listed with asterisk is either limited or restricted 22 Human Genome News, May 1991

Intentatiion:al Society of Forensic Haemogenetics; (Int.) 49/6131-172688 or -392118, September (con!.) NIH, Bethesda, MD {Jenome Sequencing Conference III; Hilton Head, SC Wallace, 301/480-0634, Fax: 301/480-8588] Gathering of Networks of Snpport Groups; Washington, DC [see contact: Sept. 14-15] International Congress of Human Genetics; ASHG, Washington, DC; [M. Ryan, ICHG, 3011571-1825, Fax: 301/530-7079]

Workshop on Mouse Genome Mapping; Lunteran, (Int.) 31/20-512-2516, Fax: (Int.) 31/20-617-2625] Impact of Human Genetic Engineering; Oak Ridge, TN 615/483-4357] Human Genome III: The International Conference on the Status and Future of Human Genome Research; San Diego, CA [ScheragoAssoc., Inc., 212/730-1050, Fax: 212/382-1921] and Journalism III. Genes and Human Behavior: A New Era?; MA [J. Beckwith, 617/432-1920] Justice and the Human Genome; Chicago, IL November 8-9 [Conference Registrar: 312/996-5225, Fax: 312/996-5227] * Attendance at meetings listed with asterisk is either limited or restricted.

of Recombinant DNA in Eukaryotic Systems; CVA, DC [M. Miller, 202/319-6161, Fax: 202/319-5721] Recombinant DNA Thcbniques; Rochester Institute of Technology, NY (also June 10--14 and Nov. 1&--22) [Co Miller, 716/475-5977] .. cDNA Library Workshop; LT!, Germantown, MD (also October 7-12) [G. Tinney, 800/828-6686, Ext. 713 or 301/921-2250, Fax: 301/258-8212] Recombinant DNA Methodology; Exon-Intron, Inc. , Columbia, MD (also offered July &--12, Aug. 7-9, Sept. 9-13, and other times) [&on-lntron, 301/730-3983] Recombinant DNNCytogenetic Approaches to Genetic Disease and Gene Mapping; CVA, Washington, DC [see contact: May 29-31] Genetic Toxicology; Gordon Research Conferences, New London, NH IA. Crnickshank, 4011783-4011, 4011783-3372, Fax: 401/783-7644] TIssue Culture and Hybridoma Thchniques; Rochester Institute of Technology, NY (also Nov. 18-22) [see contact: June 3-7] Recombinant DNA Techniques II; LT!, Germantown, MD (also July 15-20, September 23--28) [see contact: June 3-8] . Basic Cloning Techniques; BTF, st. Louis, MO (also offered June 1&--21 at Colorado Springs, CO; July 9-12 at New York, NY; and other dates and . locations) [So Chance, 515/232-8306, 1:00--5:00 p.m. CST] Plant Molecular Biology; Gordon Research Conferences, Andover, NH [see Gordon contact: June 10-14] DNNPCR for Diagnosis of Microbial and Neoplastic Disease; Washington, DC [see contact: May 29-31] Diagnosis using PCR and Hybridization Analysis; BTP, Diego, CA [see contact: June 11-14] Human Genome News, May 1991 23

o[ Flow Cytometry: Hands-On Training in Molecular Bi(.lo!O' Techniques; BTP, Colorado Springs, CO [see LIl"Kllgeand Chromosome MappinwSequence Analysis: Courses at V.K. Hlllm"m r~e.n.orr>e Mapping Project Resource Centre; Harrow, England offe>redJuly 8-12, July 15-19) [CO Bates, (Int.) 44/81-869-3446,

DNA-Related Methods in Hnman Genetics: YAC Cloning in Genome Analysis; London [P. Faik, (Int.) 44/71-403-6998] DNA Amplification by PCR; BTP, (also offered July 22 at St. Louis, M 0 and other dates contact: June 11-14] Protein and Nucleic Acid Separation Techniques; CVA, Washington, DC [see contact: May 29-31] Recombinant DNA Techniques I; LT!, Germantown, MD (also Sept. 16-20, Nov. 11-15) [see contact: June 3--8] & Genetic Basis for Cen Proliferation; Gordon Research Meridan, NH [see contact: June 10-14] Analysis; BTP, Houston, TX (also offered July 23-26, Aug. 6-9, and locations and times) [see contact: June 11-14] Topics in Recombinant DNA; Exon-Intron, Columbia, MD [see contact: June 5-7] & Gene Expression; Gordon Research Conferences, . June 10-14]

Exon-Intron, Columbia, MD [see contact: June 5-7] Research Conferences, Newport, RI

Genomic Analysis 4-24 and Protein Sequence Analysis Workshop [or Biomedical August I~~~!::~_~~~~~ Pittsburgh Supercomputing Center, Pittsburgh, PA [N. Kiser, 5-9 I, or 1-800/222-9310 (PA), 1-800/221-1641 (U.S. outside PAl; Ihlte,·net· [email protected],BITNET: [email protected] Isolation and Characterization; Exon-Intron, Columbia, MD [see contact: JUlie 5-7] View, CA (Registration deadline: Sept. 3) Inc., 415/962-7300] and Genetic Manipulation o[YACS; CSHL, Cold Spring Harbor; deadline: July 15 [CSflL, 516/367-8346, Fax: 516/367-8845J

October Molecular Genetics of Fission Yeast; (application deadline: July 15) [see contact: Essential Computational Genomics Cor Molecular Biologists; Cold Spring Harbor (application deadline: July 15) [see contact: Oct. 8-21] Genomic InCormationlEthical Implications; . (application deadline: July 19) [I. Boulanger, PC/Gene; Mountain View, CA (Registration deadline: Oct. 28) [see contact: Sept. 16-19] 24 Human Genome News, May 1991

Acronyms listed were AAAI American Association for Artificial Intel· LLNL' Lawrence Uvermore National Laboratory, ligence Uvermore, Calif. chosen because they ASHG American Society of Human Genetics LTI Ufe Technologies, Inc. were either used in the NClt text or are relevant to ATCC American Type Culture Collection National Cancer Institute (NIH) the human genome BTP Biotechnology Training Programs NCR National Cell Repository research community. CBSC Carolina Biological Supply Company NCHGRt National Center for Human Genome Research (NIH) Listed in parentheses eDNA complementary DNA NICHDt National Institute of Child Health and after an organization CEPH Centre d'Etude du Polymorphisme Human Development (NIH) Humain is the branch of NIGMSt National Institute of General Medical CRADA Cooperative Research and Development Sciences (NIH) government or the Agreement organization to which NIHt National Institutes of Health CSHL Cold Spring Harbor Laboratory it is responsible. NLGLP' National laboratory Gene Ubrary Project CUA Catholic University of America (LANL, LLNL) *Denotes U.S. Department DHHS Department of Health and Human NSF National Science Foundation of Energy organizations. Services (U.S.) OER' CHlce of Energy Research tDenotes U.S. Department DOE Department of Energy (U.S.) OHER' Office of Health and Environmental of Health and Human FISH flourescence in situ hybridization Services organizations. Research (OER) GDB Genome Data Base (HHMI, Johns ORNL* Oak Ridge National Laboratory, Hopkins University) Oak Ridge, Tenn. HGM Human Gene Mapping Workshop OTA Office of Technology Assessment HGMIS' Human Genome Management (U.S. Congress) Information System (ORNL) PACHGt Program Advisory Committee on the HGN,t Human Genome News Human Genome (NIH) HHMI Howard Hughes Medical Institute PCR polymerase chain reaction HUGO Human Genome Organisation PHLS Public Health Laboratory Service (U.K.) [International] RFLP restriction fragment length polymorphism ICHG International Congress of Human Genetics SBIR Small Business Innovation Research IMACS International Association for Mathematics SIMS Societal Institute of the Mathematical and Computers In Simulation Sciences LANL* los Alamos National Laboratory, STM scanning tunneling microscope los Alamos, N,M, STS sequence tagged site LBL* Lawrence Berkeley Laboratory, Berkeley, Calif. YAC yeast artificial chromosome

Human Genome Management Information System HGMIS MAILING ADDRESS Subscription/Document Request (Vol. 3, No.1) Betty K Mansfield 1. Human Genome News Oak Ridge National Laboratory _ New Subscriber _ Change of Name/Affiliation/Address _ Drop Name from mailing list P.O. Box 2008 Oak Ridge, TN 37831-1;050 2. - Human Genome Information Database Comments: 3. - DOE Human Genome 1989-90 Program Report 4. - Understanding Our Genetic Inheritance, The U.S. Human Genome Project: The First Five Years, FY 1991-1995 (Joint DOE-NIH 5-Year Plan) 5. - DOE Contractor-Grantee Workshop Report (complete report with abstracts)

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