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ISSN: 1050-6101 Vol. 7, No.2, July-August 1995 Optical Mapping Offers Fast, Accurate Method for Generating Restriction Maps New Approach Eliminates Electrophoresis, Is Amenable to Automation

evelopment of cheaper and faster technologies for large-scale Dgenome mapping has been a major priority in the first 5 years of the Project. Although many efforts have focused on improving standard gel electrophoresis and hybridization methods, a new approach using optical detection of single DNA mole.cules shows great promise for rapid construction of ordered genome maps based on restriction endonuclease cutting sites. l -4 Restriction endonucleases-enzymes that cut DNA molecules at specific sites in the genome-have played a major role in allowing investigators to identify and characterize various loci on a DNA molecule. Unlike maps based on STSs (a sequence-based landmark), restriction maps provide the precise genomic distances that are essential for efficient sequencing and for determining the spatial relationships of specific loci. Compared with hybridization-based fingerprinting approaches, ordered restriction maps offer relatively unambiguous clone characterization, which is useful for determining overlapping areas in contig formation, establishing minimum tiling paths for sequencing (coverage of a region), and characterizing genetic lesions with respect to various structural alterations. Image of a human 11 YAC clone (425 kb) cleaved by restriction endonucleases, Despite the broad applications of restriction maps, however, associated stained with a fluorochrome, and visualized by techniques for their generation have changed little over the last 10 years fluorescence microscopy. (White bar at lower left because of their reliance on tedious electrophoresis methods. Optical mapping corner represents 10 11m.) of single DNA molecules represents the first practical nonelectrophoretic genomic-analysis approach toward producing ordered restriction maps.

Visualizing Gaps in a DNA Molecule Ordered optical restriction maps were first constructed from yeast chromo­ In This Issue somes by fluorescence microscopic imaging of stained DNA molecules treated with restriction enzymes.' In this method, individual fluorescently Page labeled DNA molecules were elongated on a microscope slide in a molten 1 Optical Mapping Offers Fast Method agarose flow containing restriction endonucleases. Resulting cleavage 2 DiGeorge Syndrome Region Cloned events were recorded by fluorescence microscopy as time-lapse digitized 3 Hudson Heads NCHGR Policy Office images; cut sites appeared as gaps that widened as DNA fragments 3 Poll Shows Interest in Genetics relaxed (see figure at right). Fragment order was apparent throughout the 3 News from Baylor procedure, and maps were constructed by measuring fragment sizes via 4 Fox Chase Team Wins Award relative fluorescence intensity or apparent length measurements. In addi­ 4 DOE Postdoctoral Fellows Named tion to high throughput and high resolution, advantages of optical mapping 4 EEOC Guidelines Clarify "Disability" include a very small sample size and the elimination of radioactive label­ 5 Workshop ing required in conventional methods. 6 ACEDB Version 4.0 Debuts Modifications for Other Vectors 7 Colloquy Explores Genetic Predisposition Improvements to the original optical mapping method now allow analysis 8 Using RH Mapping, Rhserver of a wide range of such cloning vectors as cosmid, bacteriophage, P1, and 9 GDB Forum: Web Server; Submissions YACs and produce accurate maps consisting of DNA fragments as small 10 Calendars as 500 bp. These improvements include eliminating agarose and time-lapse 11 Funding/Grants imaging and fixing the elongated DNA molecules onto polylysine-treated 12 Subscriptions; Selected Acronyms glass surfaces. To analyze lambda clones, DNA samples have been fixed 2 Human Genome News July-August 1995

Genome News onto derivatized glass surfaces by sandwiching miniaturization. The advantages of optical map­ them between a treated coverslip and glass slide. ping-high throughput and resolution, safety, A cooled CGO camera was used to image mole­ and low cost-are likely to aid rapid progress in A longer review article cules from 28 kb down to 800 bp3; more recent genome analysis and contribute significantly to on this topic by David experiments have lowered the resolution limit to the accelerating pace of the Human Genome Schwartz and his col­ about 300 bp. Sizing errors are comparable to Project as well as to efforts directed toward leagues is in print in and in many cases lower than the rate achievable mapping human disease and other ge­ Issue 1 of Genome by agarose gel electrophoresis, depending on the netic alterations. {David C. Schwartz (NCHGR Research, published by number of molecules analyzed. grantee, New York University) and Akhtar Samad Cold Spring Harbor (Cornell Medical Callege)] 0 Laboratory Press and Generating Y AC Maps available online, with Although a large fraction of the human genome is References downloadable video covered by YAC contigs, few YAC restriction maps 1D.C. Schwartz, X. Li, LI. Hernandez, S.P. Ramna­ sequences of the have been generated. Using optical mapping, rain, E.J. Huff, and Y.-K.wang. Science 262, 110 (1993). technique in action ordered YAC restriction maps have been con­ 2X. Guo, E. Huff, and D.C. Schwartz. Nature 359, (http://www.cshl.arg:80/ structed,4 with overall relative sizing errors com­ 783 (1992). journal/grlsupp/ement). parable to routine pulsed-field gel electrophoretic 3X. Meng, K. Benson, K. Chada, E. Huff, and analysis. Ordered restriction maps have now been D.C. Schwartz. Nat. Genet. 9, 432 (1995). generated for the human Beckwith-Wiedeman 4W. Cai, D.E. Housman, Y. Wang, and D.C. locus [with David Housman (Massachusetts Insti­ Schwartz. Proc. Nat!. Acad. Sci. (USA) 92. 5164 tute of Technology)], the BRCA2 locus [with Stu­ (1995). art Fisher (Columbia University)], and the mouse olfactory locus [with Richard Axel (Columbia Uni­ versity)]. Optical maps are currently being gener­ ated from phage, cosmid, YAC, and BAC clones. DiGeorge Syndrome

Large-Scale Genome Mapping Region Cloned High-throughput approaches are being devised in Candidate Genes Identified anticipation of the vastly increased requirements for whole-genome analysis. Fully automated opti­ esearchers led by Beverly Emanuel cal mapping approaches would require no human R and Marcia Budarf at Children'S Hospi­ intervention between sample preparation and tal of Philadelphia have cloned a region of map construction and hold enormous promise for the chromosome 22 long arm containing a chromosomal breakpoint involved in DiGeorge syndrome (DGS) and have identi­ ... Biological Resources fied candidate genes spanning the break­ Mapped Genomic Reagents Resource point [Nat. Genet. 10, 269-78 (July 1995)]. More than 3200 human BACs and 250 PACs are now available from the Mapped Named for endocrinologist Angelo DiGeorge, Genomic Reagents Resource. The DOE-funded resource is headed by Julie Korenberg who first described the syndrome in 1965, the (Cedars-Sinai Medical Center and University of California, Los Angeles) and represents a collaboration with the two groups generating BAC and PAC libraries [Melvin Simon (Cali­ 22q11 microdeletion associated with DGS is fornia Institute of Technology) and Pleter de Jong (Roswell Park Cancer Institute)]. The believed to occur about once in 4000 to 5000 project aims to establish an ordered sequenceable array of human BACs as a set of sta­ births. Children born with chromosome 22- ble genome reagents that ultimately will be integrated with other vectors for sequencing, deletion disorders share several characteristics, isolation, and molecular cytogenetic markers. Plans are to provide 24,000 BACs including cardiac defects, abnormal facies, thymic rapidly and cost-effectively as molecular cytogenetic markers, stable vectors for genome hypoplasia, cleft palate, and hypocalcemia. Region mapping and sequencing, and nucleation sites for contig construction. The mapped 22q11.2 deletions may be implicated in a signifi­ clones have also been provided to Thomas Hudson (Massachusetts Institute of Technology­ cant proportion of newborns with heart defects. Whitehead Institute) to establish STS assignments. Descriptions of the resource and associated database, reagent request form, and GIF illustrations of the genome-wide Although patients have many different deletion probe distribution can be found under "Integrated YAC/BAC/PAC Resource" endpoints, researchers found that most have a (http://www.csmc.eduigeneticslkorenberg/korenberg.html).O 1.S-Mb deletion [the DiGeorge chromosomal region (DGCR)]. Deletion size has not been cor­ Coriell Cell Repositories related with disorder severity. To identify candi­ The' National Institute of General Medical Sciences Human Genetic Mutant Cell Reposi­ date genes spanning the minimal region critical tory is requesting submission of blood or Iymphoblastoid cell cultures from probands with to DGS development, researchers studied a well-documented phenotypes representing a variety of familial complex genetic disorders. In addition to familial cancers, complex disorders being sought include multiple sclerosis, rare DGS individual with a balanced transloca­ epilepsy, Parkinsonism, hypertension, atherosclerosis, long QT syndrome, osteoporosis, tion between 2 and 22. Gene tran­ asthma, rheumatoid arthritis, nonsyndromic hearing loss, neural tube defects, congenital scripts were identified by direct screening of heart disease, cleft lip and palate, fetal alcohol syndrome, morbid obesity, psoriasis, glau­ cDNA libraries, exon amplification, cDNA selec­ coma, macular degeneration, cataracts, migraine, lupus erythematosus, Crohn's disease tion, and GRAIL sequence analysis. Attention is and other inflammatory bowel diseases, autism, dyslexia, attention deficit disorder, and now focused on two genes located directly at the Tourette's syndrome. breakpoint; one of these codes for a that The National Institute on Aging Cell Repository has available for distribution cell cultures resembles the receptor, suggesting a from three of the extended pedigrees used to clone the AD3 gene for early-onset Alzhe­ possible role in developmental regulation. A imer's disease. Affected and unaffected members of the Canadian Alzheimer's disease complete cos mid contig of DGCR has been con­ pedigree FAD1 , the German FAD2, and the Italian FA04 are included in the collection. structed and is now being sequenced in collabo­ [Coriell Cell Repositories (800!752-3805 or 609!757-4848, Fax: -9737)1.0 ration with Bruce Roe (University of Oklahoma).O July-August 1995 Human Genome News 3

Genome News Hudson Heads NCHGR Policy Office athy Hudson has joined the NIH National biology from the University of California, K Center for Human Genome Research Berkeley. She has received numerous awards, (NCHGR) as Assistant Director for Policy including the Secretary's Special Recognition Coordination. As Award, Assistant Secretary for Health Special Recognition Award, and science fellowships from head of the newly the Congressional Office of Technology Assess­ created Office for ment and American Society for Microbiology.O Policy Coordination, Hudson will be responsible for the News from Baylor Office of Communica­ tions, Office of Pro­ Genome Center Reports on Gene Studies gram Planning, and The following four items were reported in Issue 14 (May 1995) of the Baylor Office of Legislation. Genome Center News (http;llgc.bcm.tmc.edu:8088Inewsletterlhome.htm0. Before joining NCHGR, To be placed on mailing list: [email protected]. Hudson was Senior Pol- Chondrodysplasia Punctata (CDPX) Region. Investigators with Andrea Bal­ Kathy Hudson icy Analyst in the Office labio [formerly at Baylor College of Medicine (BCM) and now at the Telethon of the Assistant Secre­ Institute of Genetics and Medicine (Milan)] have cloned the genomic region on tary for Health at the the X chromosome where the gene for X-linked CDPX is aSSigned. From this Department of Health and Human Services. She region three adjacent genes, presumed from their structure to have sulfatase advised the Assistant Secretary on national activity, have been isolated. Chondrodysplasia is a congenital defect of bone health and science policy issues involving NIH. and cartilage development characterized by aberrant bone mineralization, Before that, she was a Congressional Science severe underdevelopment of nasal cartilage, and short finger ends. CDPX is fellow. also implicated in a similar disorder known as wariarin embryopathy, a condi­ Hudson's training and professional experiences tion caused by the administration of warfarin (an anticoagulant drug) during a will provide focus and leadership in public policy critical 6- to 9-week period of pregnancy. [Cell 81, 15--25 (1995)] and public affairs issues relating to NCHGR pro­ X-Linked Ocular Albinism. Ballabio and Dick Lewis (BCM) have found an grams. She will coordinate NCHGR Ethical, altered gene in the Xp22.3 region in patients with X-linked ocular albinism of Legal, and Social Implications activities. the Nettleship-Falls type (OA1), a severe disorder affecting the eyes and the Hudson received her B.A. in biology at Carleton skin. [Nat. Genet. 10, 13-19 (1995)] College in Minnesota, M.S. in microbiology from Idiopathic Generalized Epilepsy (IGEl. In searching for gene loci for IGE, the University of Chicago, and Ph.D. in molecular Massimo Pandolfo, Pragna Patel, and coworkers at BCM and in Italy report that results of a study using nonparametric methods do not support linkage of IGE with markers, as was suggested previously. Their results Poll Shows Interest in Genetics point to linkage to markers on the chromosome 8 long arm; this region is being investigated further in other IGE families. [Hum. Mo/ec. Genet. 4,1201-7 (1995)] A new Harris telephone poll, conducted between April 6 and 9 for the nonprofit Center for Social Spinocerebellar Ataxia Type 1. Studies by Huda Zoghbi (BCM) and collabora­ and Legal Research in Hackensack, New Jersey, tors show that both the normal and expanded versions of the SCA1 gene are shows that the public is optimistic about the translated and protein size is correlated with expansion size. Results showing that the apparently have normal stability and distribution support the benefits but concerned about potential abuses of genetic testing and use of human DNA. Among hypothesis of a novel harmful activity associated with the CAG coding region 1000 adults nationwide, 56% said state DNA expansion. [Nat. Genet. 10, 94-98 (1995)] 0 databases containing "genetic fingerprints" of all newborns would be ''very'' or "somewhat" accept­ Search Launcher Adds Features, Interface able, and 68% would be likely to ask doctors for New additions have been exons, introns, and open • Multiple Sequence Align­ genetic tests if they were available at a reason­ made to the BCM Search reading frames to deter­ ments Page has added able price. However, the overwhelming majority Launcher \foNJW page at mine the protein-coding BlockMaker from the http://gc.bcm.tmc.edu:8088! potential of a DNA Fred Hutchinson Cancer (86%) would be concerned if employers and sequence (e.g., using Research Center. insurers used genetic tests before deciding search-launcherllauncher. GRAIL or GeneFinder). In addition, a new UNIX and whether to hire or insure someone. Some 85% html [HGN 7(1), 12 (May­ June 1995)[: • Sequence Utilities Page Macintosh batch interface to agreed that a national bioethics advisory commis­ allows conversion • Nucleic Acids Sequence the Search Launcher is now sion should be established to advise and make between different available. This program auto­ Search Page has added sequence formats; and recommendations on bioethical issues arising BEAUTY·X. a BLASTX six-frame translation, matically reads multiple from human biology research. version of BEAUTY that reverse complementation, sequences from one or adds sequence family and restriction mapping more input files, runs speci­ Center president Alan Westin (Columbia University) membership and con­ of nucleic acid sequences. fied searches in the back­ served and annotated said of the poll, "At a time of downsizing govern­ ground (one at a time), then domain information to • Protein Secondary Struc­ ment and hostility to spending tax dollars, it is quite BLAST searches. ture Prediction Page pro­ stores the results as individ­ striking that more than 8 in 10 members of the vides access to servers ual HTML documents that • Gene Feature Search with applicable programs can be read later using public believe it would be valuable to have a gov­ Page accesses servers ernment commission look into the uses of genetic as well as launches to Mosaic or Netscape. that can search nucleic e-mail servers. testing and recommend protective policies:'O acid sequences for [Randall F Smith, BCM] 0 4 Human Genome News July-August 1995

Genome News Fox Chase Team Wins Smithsonian Award Innovative Computer Technology Enables "Virtual" Centers FOX Chase Cancer Center (FCCC) Project, will ultimately help improve diagnosis A team led by Kenneth Buetow won the and prevention of disease by allowing researchers top science prize in the seventh annual Com­ to pinpoint genetic characteristics linked with NCHGR puterworld Smithsonian Awards Program. specific cancers, birth defects, and other heredi­ tary and nonhereditary disorders. Newsletter The team designed a computer technology Available that enhanced construction of a comprehen­ The map was compiled from linkage data gener­ ated during the past decade by CHLC, Genethon, NCHGR Today, a four­ sive human genetic map by the Cooperative Human Linkage Center (CHLC), a collabora­ University of Utah, Yale University, and over 100 page quarterly update CEPH collaborators. The FCCC team created tive group composed of researchers at on activities at the NIH the common database to distribute data and FCCC, University of Iowa, Harvard Univer­ National Center for maps within the project, with clients at each site Human Genome sity, and Marshfield Medical Foundation. The communicating via the Internet with a central­ Research (NCHGR) work was funded by the NIH National Center ized server maintaining the CHLC database. A Division of Intramural for Human Genome Research. number of graphic interface tools that work as Research, includes infor­ distributed applications were also developed. mation about NCHGR According to Buetow, the technology created a personnel, latest devel­ "center without walls;' establishing a new model The winning technology, which was selected opments in genetic for genome studies. Although such "virtual" cen­ from 265 nominations, will occupy a permanent research, and upcoming ters have been used in other fields, it was a first place in the Smithsonian Institution's research events.IFree subscrip­ for human genome research. collection as part of the National Museum of tion: NCHGR Office of This computerized system helped researchers American History exhibit "The Information Age: Communications complete a high-density human linkage map-a People, Information, and Technology:' The (301/402-0911, short-term goal of the Human Genome Project­ awards program was begun in 1989 by Com­ Fax: -2218, LeslieF@ a year ahead of schedule [Science 265, 1981- puterworld and the Smithsonian Institution to od.nchgr.gov)] 0 2144 (September 30, 1994) and HGN 6(4), 1, honor creative uses of information technology 14-15 (November 1994)]. This map, along with that benefit society and to identify these benefits others being developed in the Human Genome for the general public. [Innovation Network Home Page: http://innovate.si.edu, CHLC Home Page: http://www.chic.org] 0 DOE Postdoctoral Fellows Named OE has announced the award of six 1995 Human Genome Distin­ New EEOC Guidelines Dguished Postdoctoral Fellowships to conduct research for up to Clarify "Disability" 2 years at university or DOE laboratories. These fellowships were initi­ On March 15 the U.S. Equal Employment Oppor­ ated by DOE to develop tools, technologies, and resources for deci­ tunity Commission (EEOC) released official guide­ phering the molecular nature of the human genome and to support lines clarifying the meaning of "disability" as used related research. Winners were chosen from a field of applicants who in the Americans wilh Disabilities Act (ADA) of received their doctoral degrees after April 30, 1993. 1990. The guidelines extend ADA protection to Listed below are the name of each fellow, university of doctoral degree, host individuals who experience employment dis­ laboratory and research mentor, and research topic. crimination based on genetic information related to illness, disease, or other disorders. • Evan Eichler (Baylor College of Medi· • James Labrenz (University of Califor" cine): Lawrence Livermore National nia, Los Angeles): University of Wash" Referring to the ruling as a positive step, National Laboratory, HalVey Mohrenweiser. Iden" ington, Seattle (UW8), Tim Hunkapiller. Center for Human Genome Research director tification, organization, and charac" Error analysis of principal sequencing Francis Collins said, "The American people will terization of zinc finger genes in a 2·Mb data and its role in process optimization receive the full medical benefit of genetic test­ cluster on 19p12. for genome·scale sequencing projects. ing for predisposition to illness only when • Kelly Ann Frazer (University of Califor· • Marie Ruiz-Martinez [Northeastern Uni" genetic discrimination barriers are lifted." nia, San Francisco): Lawrence Berkeley versity (NU)]: NU, Barry Karger. Multi­ National Laboratory, Eddie Rubin. In plex purification schemes for DNA se· ADA defines a person with a disability as one vivo complementation of the murine mu" quencing-reaction products: application who has a physical or mental impairment that tations grizzled, mocha, and jitteri. to gel"filled capillary electrophoresis. substantially limits a major life activity, has a • Soo~in Hwang (University of California, • Todd Smith (UWS): UWS, Leroy record of impairment, or is regarded as having Berkeley): Lawrence Berkeley National Hood. Managing the flow of large·scale an impairment. Employers who make adverse Laboratory, Joe Gray. Positional cloning DNA sequence information. of oncogenes on 20q13.2. employment decisions based solely on genetic predisposition are regarding the individual as These fellows are the last to be appointed under this program. In the future, having an impairment, which is covered in the human genome researchers will be eligible for the Alexander Hollaender third part of the definition. Thus, these employ­ Distinguished Postdoctoral Fellowships, which offer appointments in the life, ers would be in violation of ADA. [Copies of biomedical, and environmental sciences. The next application deadline is ADA Guidelines: Write to EEOC; Office of Com­ January 15, 1996. For information on this and other postdoctoral opportuni­ munications and Legislative Affairs; 1801 L St., ties, see contact information on p. 11.0 NW; Washington, DC 20507] 0 July-August 1995 Human Genome News 5

Genome News Chromosome 9 Workshop Produces New Maps he Fourth International Workshop on segments derived from four mouse chromo­ somes. The information is sufficient for polarity This article was excerpted TChromosome 9, held April 23-25 in from the electronic meeting determination in these homologous segments; Williamsburg, Virginia, was organized by report. Margaret Pericak-Vance (Duke University) none is astride the human centromere. and attended by 33 people from 7 countries. Resources Sponsors included the U.K. Medical Research Hybrids. Allen Bale (Yale University) reported Chromosome g Council, DOE, NIH National Center for the submission of four hybrids containing Human Genome Research, and the Human defined 9q deletions to Coriell. Other hybrids, Workshop Genome Organisation (via a grant from the available from David Callen (Adelaide Children's Information European Community). Hospital), contain possibly useful breakpoints Available on chromosome 9 involving balanced transloca­ Workshop reports, abstracts, Speaking of the meeting's success, A. Jamie tions with chromosome 16. maps, and figures are avail­ Cuticchia [formerly Genome Data Base (GDB), able by anonymous ftp now at Mitre Corporation] said, ''The chromo­ Clones. The chromosome 9 cosmid library from (ftp.gene.ucLac.ukor some 9 workshop is noteworthy because for the Lawrence Livermore National Laboratory contin­ 128.40.82.1) in the subdirec­ first time on record every participant submitted ues to be a valuable tool. A new section of the tory /publc9workshop/1995 data to GDB before the meeting. Recognizing that Chromosome 9 Home Page will include a list and or via the Chromosome 9 searchable data is critical in creating integrated free text information about cosmids in this library Home Page (http://www.gene. maps, the chromosome 9 community required that identified by the 300-microtitre-plate notation. ucl.ac.uklchr9home.html). An integrated chromosome 9 ALL data be submitted in advance." New data or comments about the section should be sent to John Attwood (john@mrc-hbgu. map can be found in the location database LDB Continuing a previously effective format, individual ucl.ac.uk). A second chromosome 9 cosmid participants made brief presentations of their inter­ (accessible via the chromo­ library has been constructed in the vector super­ some 9 Home Page and ests and research highlights since the last meet­ cos [Murrell et aI., Genomics 25, 59-65 (1995)]. ing, and leaders of small working groups provided http://cedar.genetics.soton.ac. Some YACs from the chromosome 9-specific uklpublic_html). The map information on the latest findings. Chromosomal library constructed by MaryKay McCormick can also be obtained by subgroups worked independently and then jointly (Massachusetts General Hospital) are freely anonymous ftp as the file to produce consensus physical and genetic maps. available, and others are distributed on a col­ /publchmm9/map from A new subsection on morbid anatomy was added laborative basis. In addition to the 160 or so Jip:/lcedar.genetics.soton. to handle emerging correlations of mapped disor­ cloned genes known on chromosome 9 and ac.uk. SIGMA is available ders with localized potential candidate genes. listed in GDB, 215 ESTs were added in the past via anonymous ftp Selected meeting highlights follow. year. The total of 330 ESTs presently identified {ftp.ncgr.org)andWWW (http://www.ncgr.org/sigmal includes 108 from Charles Auffray (Genethon). Mapping home.html). ESTs become increasingly valuable resources Global Map. The composite genetic linkage map as the rate of EST mapping increases in was modified and updated during the meeting genomic radiation hybrids. using a set of defined linkage data and SIGMA, a 1996 Chromosome g software program developed by Michael Cinkosky Polymorphic Markers. GDB lists 341 polymor­ Workshop Planned (formerly Los Alamos National laboratory, now at phic loci on chromosome 9. Of these, 286 are A fifth workshop is tenta­ University of Utah Medical Center). Lack of telo­ short tandem repeats (159 dinucleotides, 22 tively planned for fall meric markers continues to be a problem, but trinucleotides, and 105 tetranucleotides). Sev­ 1996 to bring various recent efforts have clarified the order of and dis­ eral new polymorphic markers were contributed mapping issues to clo­ tance between markers near each telomere; genetic at the meeting, including approximate map posi­ sure. Brandon Wain­ distance in. these regions has been reduced signifi­ tions for 43 new tetranucleotide repeats from wright (Center for cantly as well. The map is most remarkable for the Utah Marker Development Group (UMDG). Molecular Biology and uneven marker distribution, with several clusters Meiotic BreakpOints. Two groups reported algo­ Biotechnology) will host of anonymous markers. This suggests that certain rithms concerned with defining meiotic break­ the meeting in Brisbane, genomic regions have enhanced clonability prop­ points in the CEPH families. Steve Gerken Australia, because of erties, unusually high polymorphism rates among (UMDG) aims to construct maps, and Attwood the number and diver­ markers, low genetic-recombination rates, or a sity of chromosome 9 combination of these factors. plans to produce a panel of well-supported breakpoints that can be used for rapid place­ research groups there. Morbid Anatomy. Six new Mendelian disease loci ment of new polymorphic markers. All break­ were identified by genetic linkage or physical map­ points generated by Attwood are available via ping to chromosome 9. These are hyperglycine­ the Chromosome 9 Home Page (see sidebar mia, isolated, nonketotic type 1 (GLDC); venous for address), which contains an interactive form malformations (VMCM); familial melanoma for requesting breakpoint details for any speci­ (CDKN2); arthrogryposis (AMCD1); male pseudo­ fied chromosomal region. hermaphroditism (HSD17B3); and Osler-Rendu­ Weber disease, type 1 (ENG). Community Goals Comparative Mapping. Publication of the results Specific community goals set at the workshop of 50 cross-hybridizations between products of include (1) extending information on the ease of human chromosome 9 and the mouse genome using genetiC markers and (2) coordinating across has provided a detailed comparative map. The numerous groups the refining of meiotic break­ chromosome now has known syntenies with eight point mapping of many microsatellite markers.O 6 Human Genome News July-August 1995

Genome News ACEDB Version 4.0 Debuts at Annual Meeting Workshop ince its 1991 introduction for the goals were code development and consolida­ Documents S Caenorhabditis e/egans community, tion, database building, documentation writing, interest~group discussions, and long-range http://probe.nalusda.gov: ACEDB has served as a data-management 8000/acedocs/oce95/ model for other research projects and has planning. Investigators agreed to continue their collaborations after the meetings ended. For index.hlml been adopted by a number of diverse organi­ the first time, WWW was used extensively zations and individuals to maintain and dis­ before, during, and after the conference and tribute data on more than 40 genomes, workshop to circulate instructions, document including human, bovine, Drosophila, yeast, drafts, and meeting summaries. mycobacteria, Arabidopsis, grains, trees, Selected meeting highlights are described and fungi. At the May ACEDB confer­ 14-29 below; details are given in a series of WWW ence and workshop in Geyserville, Califor­ pages (see address in left column). nia, participants represented 10 countries, 4 continents, 38 organizations, 20 data­ Meeting Highlights bases, and 19 organisms. • First public release of ACEDB version 4.0. Several curators converted their data models John McCarthy [Lawrence Berkeley National and databases to take advantage of new fea­ Laboratory (LBNL)] organized this year's meet­ tures, and programmers modified software ing. Sponsors included DOE, NIH National modules to conform with version 4. During the Center for Human Genome Research, U.S. workshop a number of bugs were identified Department of Agriculture, National Science and eliminated [report bugs to the ACEDB Foundation, and European Data Resource for newsgroup ([email protected])]. The current Human Genome Research. Conference hard w release version is 4.1, available via ftp ware and software were provided by LBNL, (nchi.nlm.nih.govlrepository/acedb). Digital Equipment, Sun Microsystems, Silicon • Software enhancements to run multiple Graphics, Network Computing Devices, ACEDB clients for different databases, linked Microsoft, and Stanford University. together via Perl scripts and HTTP servers The main goal of the 3-day conference, attended [Doug Bigwood and John Barnett (National by about 70 people, was information exchange Agricultural Library (NAL}), Jeroen Coppieters via tutorials, oral presentations, posters, online (European Bioinformatics Institute), Jean Thierry-Mieg (Centre National de la Recher­ demonstrations, and discussions. Some 45 peo~ pie stayed on for the 10-day workshop, whose che Scientifique), and Steve Rozen (Massa­ chusetts Institute of Technology)].

. • Module for displaying multiple maps, including different levels (e.g., cytogenetic bands, STS 'It ACEDB Application Examples locations, P1 clones, and DNA sequences) of the same region [Arun Aggarwal (LBNL)). Encyclopaedia of Drosophila 2.0 • Substantial progress on a prototype protein­ Of the many groups using ACEDB, the Genome Project has made the great­ Drosophila sequence display module [Eric Sonnhammer est number of modifications to the program for their specialized needs. ACEDB was origi­ (Sanger Centre)]. nally customized for use with Drosophila by Suzanna Lewis and Gyrus Harmon [Berkeley Drosophila Genome Project (BDGP)] to produce Flydb, the laboratory database of BDGP. • HTML documentation for map display and MacAce, the Maclntosh~compatible version of ACEDB, was written by Frank Eeckman sequence-assembly modules [Sam Cartin­ (Lawrence Berkeley National Laboratory), Richard Durbin (Sanger Centre), and Harmon. hour (Texas A&M and NAL), John Morris This Macintosh version was further customized by Harmon and Lewis for the Encyc{o~ (Massachusetts General Hospital), and Kate pasdla of Drosophila (fiolD), which is a jOint product at BDGP (http://fly2.berkeley.edu) Rice (Sanger Centre)]. The documentation and FlyBase (http://morgan.harvartLedu}.EolDdisplayspublishedand unpublished working group recommended using HTML for BDGP data as well as data collected by FIyBase from the scientific literature and other all future ACEDB documentation. genome projects. Since Release 1.0 became available in April, Fty8ase and BDGP have distributed more than 1500 copies of the EolD CD· ROM, giving nthe largest instal/ed user • More than 20 different software tools listed for base of any ACEDB implementation. Release 2.0 is now available on CD-ROM for the converting data to and from .ace files and vari~ Macintosh ($15, including 36-page reference manual) and by ftpforthe UNIX version. ous formats such as spreadsheets, Medline, [Ordering information and computer requirements: eofil-·sales@ltU)rgan.harvard.edu] <> and FASTA [Detlef Wolf (Integrated Genomic Database) and query tools working group]. Sanger Centre 22ace • ACEDB conversion begun for Windows-NT The first release of the human chromosome 22 physical mapping, database 22ace by Richard Bruskiewich (University of British from the Sanger Centre is now available by ftp fromftp.sanger:ac_uk in the directory Columbia), Richard Durbin (Medical Research publhumanlchr221physicaUnap. The database Is Implemented in version 4.1 of ACEDB. Council, UK), Thierry-Mieg, and others. Details about ACEDB and the Chromosome 22 mapping group can be found on WWW (http://ww",sange

Genome News Colloquy Explores Genetic Predisposition -cr-cr Notice n Interdisciplinary Colloquy on Genetic from being completely rebuilt. He thinks biology to DOE A Predisposition, organized by Pilar Os­ is ready for a new foundation that couples the Contractors sorio (University of California, Berkeley) and theory of evolution, which underlies all biological Michael Yes ley (Los Alamos National Labora­ thinking, to the mechanisms of gene expression and Grantees in a cellular, developmental, and environmental The fifth DOE Human tory) and sponsored by the Ethical, Legal, context. and Social Issues (ELSI) component of the Genome Program DOE Human Genome Program, was held Dorothy Nelkin (New York University) illustrated Contractor and Grantee last fall in Washington, D.C. The diverse predisposition concepts that appear in popular workshop will be held group of invitees included scientists; DOE culture. Beliefs in biological determinism from January 28-February 1, earlier this century are perpetuated today in the 1996, in Santa Fe, New and NIH grantees and staff; consumer group idea of genetic predisposition. A common theme Mexico. At least one representatives; social scientists; philoso­ is that people are not responsible for behavior investigator from each phers; members of the NIH-DOE Joint Ethi­ because it is predestined by their genes. This funded project is cal, Legal, and Social Implications Working theme also appears in discussions of alcohol­ expected to attend the Group; and a theologian. ism and other addictions, including smoking, entire meeting and rep­ overeating, and gambling. Now, Nelkin finds, resent the project at Francisco Ayala (University of California, Irvine) some popular stories suggest that success poster sessions. Some reviewed the meeting's purpose, which was to and failure are encoded in genes. Popular projects will also be repre­ explore genetic predisposition from multiple per­ assumptions about genetic predisposition over­ sented in platlorm presen­ spectives and identify points of agreement and simplify the complexities and contingencies tations. Registration and disagreement, questions for future discussions, expressed in scientific descriptions of these con­ abstracts are due Octo­ and areas for policy development. Genetic predis­ cepts. Deterministic assumptions about genetic ber 6 to Sylvia Spengler; position was chosen as the topic because of its predisposition are especially striking in Ameri­ Human Genome Pro­ interdiSciplinary relevance. can society, Nelkin said, where the very founda­ gram Coordination; Referring to the nature-nurture controversy, Ayala tion of the democratic experiment is based on 459 Donner Laboratory; discussed heritability and the extent to which the improvability, indeed the perfectibility, of all Lawrence Berkeley genes and environment determine a particular human beings. National Laboratory; trait. He said heritability is usually defined incor­ Berkeley, CA 94720 In his presentation on Genetic Predisposition rectly as the contribution of genes to a trait, (510/486-4879, and the Practice of Medicine, Eric Juengst whereas a correct definition would be the contribu­ Fax: -5717, sylviaj@ (Case Western Reserve University) contrasted tion of genetic variation to phenotypic variation. ux5.lhl.gov).O the metaphors of fortune teller and weather Ayala pointed out that heritability can vary drasti­ forecaster. He suggested that genetic predic­ cally from 0 to 100% for the same trait in the same tions are probabilistic, like weather forecasting, organism. To illustrate his point, he used examples and will vary according to local environment. New HGMIS from biomass studies of a cinquefoil plant under varying natural conditions. Juengst used illustrations to explain how people Telephone, think about predisposition in the clinical setting Fax Numbers In his presentation on Gene Expression in Con­ and how patients see themselves. The major text, Chris Fields (National Center for Genome ways of understanding how people think about The HGMIS area Resources) suggested looking at other disciplines genetiC disease and its social implications flow code has changed for more precise concepts about genetic predispo­ from two 19th-century models: "constitutional from 615 to 423. sition. He raised questions about the nature of predisposition" and "specific causation:' Environ­ genes and inheritance and suggested that a long­ mental conditions mayor may not be important New numbers: term, multigenerational view is needed when in gene expression. • 423/576-6669 genetics is discussed. The group extensively discussed each presenta­ • Fax: 1574-9888 Fields continued that experiments on model organ­ tion and the meaning of predisposition. isms in controlled environments don't reveal much about the range of gene expression and pheno­ Summary typic variation in a natural setting. For the last 20 Participants recommended follow-up studies This newsletter is prepared to 25 years, molecular biologists have used homo­ and discussions on predisposition and such at the request of the DOE geneous model organisms and have studied bio­ related topics as informed consent, screening, Office of Health and Envi­ logical mechanisms in controlled environments. and people's reactions to test results.O ronmental Research and Extrapolating from laboratory organism studies to the NIH National Center for the heterogeneous human population is not Human Genome Research '11 Magazine on Biophotonics by the Biomedical and Envi­ always possible. ronmentallnformation Anal­ Fields emphasized the need for scientific meas­ Biophotonics International is a new bimonthly ysis Section of the Health magazine designed to provide the latest information urements and for a language that describes the Sciences Research Division on photonic products and systems to researchers at Oak Ridge National level of complexity both in environmental action and industries that are using photonic technology Laboratory, which is man­ and in gene or other biological mechanisms. He in medical or biotechnological products and proce­ aged by Lockheed Martin believes biology is in a position analogous to that dures. The magazine will address solutions for Energy Systems, Inc., for of physics in the last century, when a great deal of both clinical and research applications. [Laurin the U.S. Department of progress and optimism were prevalent but the con­ Publishing Co.: Pittsfield, MA (413/499-0514, Energy, under Contract ceptual foundation was only a year or two away Fax: 1442-3180, [email protected])]O DE-AC05·840R21400.0 8 Human Genome News July-August 1995

Genome News ~uman Using RH Mapping, Rhserver To Incorporate Genome Human ESTs, STSs with Linkage Maps news eiotic linkage maps consisting of highly The list includes linked markers, LOD score of Mpolymorphic, PeR-based markers each link, and distance in centirays between This newsletter is intended to spanning the human genome have had a linked markers. For this RH set, one centiray is facilitate communication among equal to about 30 kb. genome researchers and to tremendous impact on the positional cloning inform persons interested in of human disease genes in recent years. Based on the scoring of 313 STSs derived from genome researdl. Suggestions The availability of cDNA sequences repre­ cDNA sequences, investigators have found are invited. senting the majority of human genes prom­ that any random marker has a 50% chance of linking with a LOD of 6 or higher to one of the Human Genome Management ises to have an equally dramatic impact on Information System human genetic research over the next few framework markers; this link will represent a Oak Ridge National Laboratory years. Efficient strategies for using cDNA valid map assignment more than 97% of the 1060 Commerce Park, MS 6480 sequence information to identify human dis­ time. As the number of SHGC-scored markers Oak Ridge,TN 37830 increases, so will the probability of linkage. 423/576-6669, Fax: 1574-9888 ease genes will incorporate partial human http://www.ornl.govl cDNA sequence STSs with meiotic linkage r------, TechResourceslHuman_ , , maps. However, despite recent technical , Research Genetics, Inc. [800/533-4363 ' Genomelhome.html (U.S. and Canada), Fax: 2051536-9016, Managing Editor advances in both physical and genetic map­ Betty K Mansfield ping, determining the order and distance ! http://www.resgen.com] I L ______~ [email protected] between large numbers of DNA markers at EditorsIWritersIDesigners the 0.5- to 1-Mb resolution level remains a Rhserver will be updated periodically to reflect Anne E. Adamson difficult task. additional scoring information from SHGC. All Denise K. Casey Judy M. Wyrick The Stanford Human Genome Center (SHGC) scoring information sent to rhserver by other Production Assistants has generated a set of 83 "whole-genome" radia­ laboratories is confidential and is not examined Murray Browne tion hybrids (RHs) that has proven very useful or retained by SHGC. For scientists who wish K. Alicia Davidson for producing high-resolution maps integrating to carry out additional analyses not provided by Larry W. Davis rhserver, raw scoring data for the framework Sheryl A. Martin human cDNAs with meiotically ordered polymor­ Marissa D. Mills phic markers. Each hybrid retains about 18% of markers is available by lip from shgc.stanford. Laura N. Yust the entire human genome with an average frag­ edu or from the EBI RHdb below. To receive ment size of 4 Mb. Scoring 6000 random mark­ the current set of instructions for using rhserver, NEWSLETTER SPONSORS ers on this RH set should result in a map of the send an empty e-mail (no message body) with entire human genome averaging 500-kb resolu­ a subject line of info to [email protected]. tion, with around 50% of all markers ordered with edu. [David R. Cox, Stanford University School of odds better than 1000:1. To date, 975 markers Medicine] 0 on the Genethon meiotic linkage map have been placed on the RH set at SHGC. Given that certain human chromosomal frag­ ,..,. Informatics Resources National Center ments show instability over time and in different for Human Genome Research hybrid passages, SHGC is carrying out all map­ EBI Releases RHdb ping studies using a single large batch of hybrid The European Bioin10rmatics Institute (EMBL out­ Francis S. Collins, Director DNA prepared and distributed to the scientific station, Hinxton) has announced the release of http://www.nchgr.nih.gov community by Research Genetics. Peter Good­ RHdb, a new database for radiation hybrid map­ Contact: Leslie Fink fellow (University of Cambridge, U.K.) and Jean ping raw data. Flat files (ASCII text) are accessi­ 301/402-0911, Fax: -2218 Weissenbach (Genethon) have used a lower ble atftp:/Iftp.ebLac.uklpubldatabasesIRHdb or [email protected] dose of X rays to generate a second independent http://www.ebi.ac.uk:80IRHdbinexp.dat(experi­ set of RH DNAs, distributed as GENEBRIDGE 4 mental conditions), panel.dat (panel information), by Research Genetics. These two reagent sets and rh.da! (raw mapping data). Data submissions: see format at http://www.ebi.ac.uklRHdb;data­ should allow many different laboratories around base questions: [email protected] rhdb on the world to integrate data in much the same the subject line.O way that DNA from the common set of CEPH families is used to generate an integrated human Haplolyping Programs Available meiotic linkage map. The haplotyping programs SIMCROSS and To facilitate integration of cDNA markers and mei­ SIMWALK, developed by Daniel Weeks and col­ otic linkage markers, SHGC has established an leagues (University of Oxford and University of automated e-mail server for RH mapping infor­ Pittsburgh), are now available in the pub directory Life Sciences & Research by anonymous ftp (ftp:l/watson.hgen.pitt.edulpub). Division, OHER mation. Rhserver allows scientists who have These are programs to generate optimal haplotype scored an STS of interest on the SHGC RH panel David A. Smith, Director configurations on general pedigrees by using a to determine which of the Genethon markers map http://www.er. doe. gov/productionJ likelihood-based approach 10r correctly taking inter­ oherlhug_top.html near their STS. Submitted typing information is marker recombination fractions into account. Contact: Daniel W. Drell subjected to a "two-point" statistical analysis, and [Contact: Daniel Weeks (Fax: 412/624-3020 or 3011903-6488, Fax: -8521 rhserver returns a list of markers that link to the +44-18651742-196, [email protected] [email protected] subject marker with a LOD score of 6.0 or higher. or [email protected])]O July-August 1995 Human Genome News 9

GOB Forum * Enhancements to GOB GDB Access Via WWW Web Server The GOB Web server is available directly at the following URLs: • The WWW GOB Browser Locus Detail provides United States http://gdbwww.gdb.org/ links to mammalian homology data from Jackson Laboratory. The browser is available via the GOB Australia http://morgan.angis.su.oz.aulgdb/docslgdbhome.html Home Page (http://gdbwww.gdb.orgl). France http://www.infobiogen.frlgdbwwwl • The Probe Library Location Query allows search­ Germany http://gdbwww.dkJz-heidelberg.de! ing for probes at specific plate, row, and column locations within a selected library. Links to this query Israel http://inheritl.weivnann.ac.illgdbldocslgdbhome.html are available from the GOB Browser and the Probe Japan http://gdb.gdbnetadjp/gdb/docs/gdbhomehtml Query form. • Monthly lists of all new GOB citations include Netherlands http://www-gdb.caos.kun.nllgdbldocslgdbhome.html those entered through Medline retrievals and litera­ United Kingdom http://www.hgmp.mrc.ac.uklgdb/docs/gdbhome.html ture scanning by GDB staff. The lists, organized by chromosome, link to detailed information for each citation. "Citations Relevant to GDB" is under "GOB Other GOB node with WWW server in English: Data Submission and Related Information," located • Sweden http://www.bmc.uu.selComputing-Dept.html on the GOB Home Page. • The GOB Web server in Baltimore has been modi~ GDB User Support, Registration, Training fied to use a new file structure. As a result, the U RLs for this server have changed, and users are To become a registered user of GOB and OMIM, contact one of the User Support advised to modify their links. The GOB Web mirror offices listed below (a user may register to access both Baltimore and a remote node). sites already use the new file structure and are not Questions, problems, or user-registration requests may be sent by telephone, fax, or affected by this change.O e-mail. The Help Line in Baltimore is staffed from 9 a.m. to 5 p.m. EDT for information on accounts and training courses, technical support, and data questions. Calls Data Submitted to GOB received after hours will be forwarded to the appropriate voice mail and returned as This summer, a significant amount of mapping and re­ soon as possible. agent data was loaded into GOB electronically, either through direct submission by researchers or by down­ "GDS/OMIM and Genomic Data on the Internet" classes will be held in Baltimore on load and processing of public data by GOB staff. December 4-5. Courses related to GOB and OMIM are also offered at some of the nodes. Contact the appropriate User Support office for details. During the 1-month period between July 19 and August 18, submission of 5387 peR probes, 6100 clone User Support Offices probes, and 4983 D-segments boosted GOB totals for UNITED STATES GERMANY NETHERLANDS each object by 17%, 2%, and 7%, respectively. GOB User Support Molecular Biophysics Dept. GOB User Support Below are samples showing sites from which data was Genome Data Base DKFZ CAOS/CAMM Center received and GOB submission numbers. For information Baltimore, Maryland Heidelberg, Germany Nijmegen, Netherlands about submitted data, use the Submission 10 Query 410/955-9705 + 49/6221-42-2349 + 31/80-653391 available from the GOB Browser on any GOB Web Fax: 1614-0434 Fax: -2333 Fax: -652977 server. [Data-submission questions: [email protected]] [email protected] [email protected] [email protected] AUSTRALIA ISRAEL SWEDEN Some Data Sources and GOB 1.0. Numbers Carolyn Bucholtz Jaime Prilusky GOB User Support ANGIS Weizmann Institute of Biomedical Center Genethon GOO-598-851 Sydney, Australia Science Uppsala, Sweden Washington University GOO-600-051 + 61/2-692-2948 Rehovot, Israel + 46/18-174057 Fax: -3847 +97218-343456, Fax: -524869 dbEST GOO-601-421 [email protected] Fax: -344113 [email protected] IMAGE consortium GOO-615-188 lsprilus@weizmann. UNITED KINGDOM European Bioinformatics Institute GOO-618-869 FRANCE weizmann.ac.il Philippe Dessen Administration Whitehead Institute (MIT) GOO-626-152 INFOBIOGEN JAPAN HGMP Resource Centre Villejuif, France Mika Hirakawa Cambridge, UK. +33/14559-5241 JICST + 44/1223-494511 Fax: -5250 Tokyo, Japan Fax: -494512 11 Electronic Journal on Molecular Biology gdb@inJobiogenjr +81/3-5214-8491 [email protected] GENE-COMBIS, part of the journal Gene, is a new Fax: -8470 online electronic journal devoted to computing problems [email protected] that arise in the molecular biology field. Edited by Michael Ashburner (University of Cambridge) and Nathan Good­ man (Whitehead Institute), GENE-COMB1S includes online articles, alerting service, discussion forum, user di­ Next HGNTo Highlight Progress rectory, and recommended software. It links to other bibli~ ographical references and databases for rapid, direct On October 1, the Human Genome Project will celebrate its fifth anniversary. submission and retrieval of sequences and source codes To commemorate this event, the next issue of HGN will highlight progress mentioned in the articles. Anonymous peer reviews are made over the last 5 years in achieving project goals.O included with the papers, which are published on WWW 8 to 10 days after approval by the editors and later in identifier is required for access to all components. This hard copy in Gene. identifier is obtained through a subscription application The service is directly available to scientists at institutes (follow the option "access registration") from the GENE~ that maintain a hard-copy subscription to Gene.lndivid­ COMBIS Home Page (http://www.elsevier.nVlocate/ ual subscription charges for others will be waived for the genecombis and http://www.elsevier.comllocatel first year of operation (ending July 31,1996), but a unique genecombis). <:; 10 Human Genome News July-August 1995

Calendar of Genome Events* 14. Hamilton Smith; TIGRINIST, Rockville, MD October 1995 ...... [see contact: Nov. 9[ U.S. DEPARTMENT OF ENERGY 28-Nov. 1. Symp. on Computer Appl. in Med. OFFICE OF HEALTH AND ENVIRONMENTAL RESEARCH Care: Toward Cost-Effective Clinical Computing; January 1996 ...... Alexander Hollaender New Orleans [AMIA, 301/657·1291, Fax: '1296, 3-6. Pacific Symp. on Biocomputing; Kohala : [email protected], http://amia2.amia,orx] Coast, HI (early reg.: Oct. 2) [L. Hunter, 301/496· DISTINGUISHED November 1995 ...... 9300, Fax: -0673, [email protected] or T. Klein, ~ Postdoctoral Fellowship Program 415/476·0663, Fax: 1502·1755, ~ 5-7. 5th Inti. Workshop on Identification of Tran­ [email protected], http://cgl.ucsfeduipsblpsb.htmn Research Opportunities in Energy-Related Ufe, I scribed Sequences; Marseilles, France (abs. 11. Florence Haseltine; TIGRINIST, Rockville, Biomedical, and Environmental Sciences deadline: Aug. 15) [N. Matthews, 303/333·4515, MD [see contact: Nov. 9] Including Human Genome and Global Change i Fax: -8423, [email protected] I Plant Genome IV; San Diego (PG I, II, Research in OHER-sponsored programs 5-8. 3rd IntI. Conf. on Automation in Mapping 14-18. and lit abs.: http://probe.na!usda.gov:BOOO) • Tenable at various laboratories & DNA Sequencing; Berkeley, CA [M. Field, • Stipends $37,500 [Scherago IntI., 2121643·1750, Fax: ·1758, 510/486·6386, Fax: ·5548, [email protected] • Doctoral degree received after April 30, 1994 [email protected]] 9. Richard Roberts; Rockville, MD [TIGRI • U.S. citizens or PRA eligible B"oEast '96; Washington, DC [BioCont. : NIST Distinguished Speakers Series, D. Hawkins, 15-18. Information and appllcations; : 301/838-3501, Fax: -0209, [email protected], . IntI., 301/652·3072, Fax: ·4951J Hollaender Postdoctoral Fellowships http://www.tigr.orxl 28-Feb. 1. 5th DOE HGP Contractor· Science/Engineering Education Division Grantee Workshop; Santa Fe, NM (abs. dead­ Oak Ridge Institute for Science and Education 9-11. 4th Conf. on Molec. Nanotechnology; line: Oct. 6) IS. Spengler, 510/486-4879, P.O. Box 117, Oak Ridge, TN 37831·0117 Palo Alto, GA [Foresight Institutes, 415/324- (615) 576-9975 Fax: -5717, [email protected]] 2490, Fax: -2497,[email protected], Deadlme January 15, 1996 iftp://ftp·parc.xerox.comlpublnanolnano4.htm~ February 1996 ...... ; 12-16. 9th IntI. Mouse Genome Conf.; 5-6. NIH Nat!. Advisory Council for Human 'Ann Arbor, Mt (abs. deadline: Aug.1) [D. Miller, Genome Res.; Washington, DC [J. Ades, April 1996 ...... 716/845-4390, Fax: -8169, dmiller@mcbio. 301/402·2205, Fax: ·2218,[email protected] 11. Neal Lane; TIGRINIST, Rockville, MD med.buffalo.edu] 5-6. Intellectual Property Issues: Critical Chal­ [see contact: Nov. 9J 13-14. 4th IntI. Workshop on Human lenges for Biomedicine and Genomics; Santa 21-26. Molecular Cytogenetics; Barga, Italy I Chromosome 16; Leiden, Netherlands Fe, NM [CHI, 617/487·7989, Fax: ·7937, [GRC, 4011783-4011, Fax:-7644, ; [M. Breuning, +31-71/276-048 or -293, [email protected], http://www.xensei.coml [email protected]] 'Fax: -075, [email protected]~ conferences] 27-May 1. 37th Annual Drosophila Res. 13-15. IBEX '95; San Francisco [BioExpo, 10-14. **MBWS-96: Advances in Gene Tech­ Conf.; San Diego (abs. deadline: Dec. 1) 713/529-1616, Fax: -0936, [email protected] nol.-Therapeutic Strategies & Molecular Medi­ IS. Bernstein, 619/594·5629, Fax: '5676, .16-17. 3rd IntI. Workshop on Human cine; Ft. Lauderdale, FL (abs. deadline: Nov. 10) [email protected], http://morgan.harvard. i Chromosome 12 Mapping; Leuven, Belgium [MBWS, 800/miagene, Fax: 305/324·5665, eduidros-confhtm~ ·[P. Marynen, +32·16/34·5891, Fax: ·5997, [email protected]} May 1996 ...... pete1: [email protected]] 10-16. Molecular Mechanisms in DNA Repli­ 8-12.1996 Genome Mapping and Sequenc" 18. Chromosome 12 Genes in Human Cancer; cation & Recombination; Taos, NM [Keystone ing Meeting; Cold Spring Harbor, NY [CSHL, Leuven, Belgium [see contact: Nov. 16-17] Symp., 303/262·1230, Fax: ·1525J 5161367-8346, Fax: -8845, [email protected], 30-Dec. 1. Exploiting Transgenic Technology 15. James M. Wilson; TIGRINIST, Rockville, http://www.cshl.org] for Commercial Development; San Diego [lBC, MD [see contact: Nov. 9] 20-21. NIH Nat!. Advisory Council for Human ,508/481·6400, Fax:-7911J March 1996 ...... Genome Res.; Washington, DC [see contact: December 1995 ...... 4-6. 3rd Annual HGP: Commercial Implications; Feb.5-6J 2-6. Molecular Basis of Gene Transcription; CHI, San Francisco [see contact: Feb. 5-6] San Diego [AACR, J. Ruben, 215/440·9300, 11-14. 3rd ACMG and 27th MOD; San Training Calendar* , Fax:-9313J Antonio, TX [So Robinson, 301/571-1825, i 3-6. UHUGO Comparative Genome Organisa­ Fax: -1895, [email protected]] November 1995 ...... tion Workshop; Queensland, Australia [HUGO 14. Bruce Stillman; TIGRINIST, Rockville, MD 15-25. DNA Sequencing: Adv. Approaches, Americas, 301/654·1477, Fax: 1652'3368, [see contact: Nov. 9] Automated Methods, and Analysis; EMBL, Heidel­ [email protected]] 15-17. Chromosome 5 Workshop; Manches­ berg, Germany [W. Ansorge, +49-6221/387-355, 3-7. 3rd UNESCO Human Genome Conf.; ter, UK [M. Dixon, Tel/Fax: +44·161/275·5620, Fax: -306, [email protected]] New Delhi IS. Matsui, +33·1/45·68·3887, [email protected]] December 1995 ...... Fax: 145·67·2639J 18-20. Single Chromosome 4 Mapping Work· 7-8. Applied Molecular Evolution; IBC, shop; Bochum, Germany [0. Riess, +49-2341 4-5. GDB/OMIM and GenomiC Data on the La Jolla, CA (abs. deadline: Nov. 9) [see contact 700-3831, Fax: /709-4196, riessoby@rz. Internet; Baltimore [see p.9] Nov. 3D-Dec. 1J ruhr-uni~bochumde] 6-8. **Computer-Assisted Molecular Design 8-9. DNA Databanks & Repositories; Birming­ 21-23. Genetics Revolution: A Catalyst for Course; San Francisco (early reg.: Sept. 1) iham, AL [AFIP/ARp, 800/577-3749, Fax: 301/427· Education and Public Policy; Dallas [M. Mays, [N. MacKenzie, 415/476·1913, Fax: 1502·4690, 15001, [email protected] 214/659-5328, Fax: -5171, [email protected]] [email protected],http://nuJi.ucsfedu] 9-13. ASCB; Washington, DC [K. King, 22-24. HGM 96; Heidelberg, Germany January 1996 ...... 301/530-7153, Fax: -7139, ascbinfo@ascbjaseb. [HUGO Europe, Secretariat, +44·171/935·8085, 8-12. **Advanced Linkage Course; New York org, gopher:llgopherjaseb.org:70111ISocietiesIASCB] Fax:-8341J [K. Montague, 2121960·2507, Fax: 1568'2750, 10-12. Genome Informatics 1995; Yokohama, 24-27. Electrophoresis '96; Atlanta (abs. [email protected], http://linkage.cpmc.colum­ Japan (abs.deadline: Oct. 13) [N. Tomioka, deadline: Oct. 15) [D. Wiley, 800/627·0629, bia.eduJ Fax: +81-3/5449-5434, [email protected]. Fax: 913/843-1274, [email protected] Extended calendars and a list of organizations ac.jpJ offering training are available at http://www. I, oml.govlTechResourceslHuman_Genomei :, *Dates and meeting status may change; courses may also be offered at other times and places; home.html or from HGMIS (see p. 8 for con" tact information). I check with contact person. **Attendance is either limited or restricted. I July-August 1995 Human Genome News 11

For Your Information .. Software, Database Resources u.s. Genome Research Funding Stanford University Investigators wishing to apply for funding • Informatics: [email protected] CENSOR Software. Jerzy Jurka and Paul Klonowski are urged to discuss projects with agency • Large-scale mapping, sequencing of (Stanford University) have added CENSOR software to staff before submitting proposals. human and mouse genomes: the Pythia program developed by Aleksander Milosav­ [email protected]_ Ijevic (Argonne National Laboratory) and Jurka. This addi­ NIH National Center for Human Peterson@nihgov tion should speed up and facilitate identification, Genome Research (NCHGR) • Physical mapping technology, training, analysis, annotation, and removal (censoring) of repeti­ and special programs: BetticGraham Program announcements listed in NIH tive DNA from sequences. To run online CENSOR, send @nih.gov Guide for Grants and Contracts help message to [email protected]. The original software is • Sequencing technology development, available from the National Center for Biotechnology (gopher.nih.gov and http://www.nih.gov technology transfer, nonmammalian or 301/496-0844). Bracketed numbers Information (NCBI,jtp://ncbi.nlm.nih.govlrepository/ model organisms; CaroCDahl@nih below refer to application due dates. repbaselsojtware). gov or RoberCStrausberg@nihgov [1] February 1, June 1, and October 1; Repbase. The Repbase database for screening human [2] April 5, August 5, and December 5; DOE Office of Health and Envi­ repetitive DNA sequences was published and released [3] May 10; [4] on a continuous basis; and ronmental Research (OHER) electronically in 1992 with DOE support. Reference col~ [5] May 1 and November 15. Human Genome Program lections by Jurka's group now contain 434 prototypic ex~ Program Categories amples and consensus sequences for rodents, other • Contact for funding information or mammals, nonmammalian vertebrates, invertebrates, Research general inquiries: [email protected] and plants. Only the human reference collection is being • Ethical, legal, and social implications or 301/903-6488_ (ELSI) of human genome research, updated regularly. In addition to complex repeats, the • Relevant documents: Fellowships (PA 92-21) [1]- http://www.er.doe.govlproductionl group has compiled the 67 most abundant simple • Genome science and technology oherlhug_top.html repeats and, with NCBI support, 38 collections of known centers (PAR 94-044) [11_ repeats present but not necessarily annotated in • Informatics (PA 92-59) [1]. Alexander Hollaender Distinguished GenBank primate sequences. Repbase is accessed • New and improved technologies for Postdoctoral Fellowships through the NCBI address above. Jurka (jurka@ genomic research and analysis Research opportunities in energy-related gnomic.stanford.edu) would like to receive user com~ (PA 94-045) [1]_ life, biomedical, and environmental sci~ ments on CENSOR and Repbase.O • Pilot projects or feasibility studies for ences, including human genome, global genomic analysis (PAR 94-046) [11_ change, and supporting disciplines. Jackson Laboratory Training Next deadline: January 15, 1996 The following two resources are supported by NCHGR • Courses related to genomiC analysis • Contact: Barbara Dorsey, Oak Ridge through a grant to Janan Eppig. [Information: Mouse (PA 91-88)[11_ Institute for Science and Education Genome Informatics User Support (207/288-6445, • Individual postdoctoral and senior (615/576-9975, Fax: 1241-5219) [email protected])] fellowships in genomiC analysis and technology (PA 92-21) [2]_ Small Business Innovation Encyclopedia of the Mouse Genome. The Encyclope­ • National research service awards: Research (SBIR) Grants dia of the Mouse Genome---a software tool that pro­ - Institutional training grants in genomiC DOE and NIH invite small business firms vides a graphic display of mouse chromosome science for predoctoral and postdoc­ (less than 500 employees) to submit grant maps-runs on a Macintosh, Sun, or DEC Alpha work­ toral trainees (PA 94-085) [3]- applications addressing the human genome station. Data files include the most current Chromosome - Individual predoctoral student fellow­ topic of SBIR programs. The two agencies Committee reports and Massachusetts Institute of Tech­ ships for disabled (PA 95-028) [5] and also support the Small Business Technology nology mouse genetic maps. The encyclopedia can also minorities (PA 95-029) [51_ Transfer (STIR) program to foster transfers interact with the Mouse Genome Database (MGD). • Special emphasis research career between research institutions and small busi­ Current versions of the software (1.0A13 for Macintosh, awards in genomic research nesses. Contacts: 3.0A2 for UNIX) and data files can be downloaded from (PA 91-89)[11_ • Kay Etzler; c/o SBI R Program Man­ ager, ER-16; DOE; Washington, DC WWW using the "Encyclopedia of the Mouse Genome" Special Programs link on the Mouse Genome Informatics Home Page 20585 (301/903-5867, Fax: -5488)_ • Minority institution travel awards DOE SBIR due March 1, 1996; STIR, (http://www.injormatics.jax.org).lnstructionsarealsopro­ (PA 91-17) [4]_ early 1996_ vided to configure Netscape and Mosaic for MGD and • Research supplements for underrepre~ • Bettie Graham (see contact, NCHGR). encyclopedia interaction. sented minorities and disabled [4]. NIH SBIR due April 15, August 15, and December 15. STIR, December 1. MGD. (http://www.informatics.jax.org) and a mirror site NCHGR: 3011496-7531, Fax: 1480-2770 for the European research community (http://mgd.hgmp. • ELSI: [email protected] National SBIRISTTR conferences: Salt mrc.ac.uk) are now available on WWW.lmprovements in 301/402-4997 _ Lake City, UT (October 3D-November 1); Release 2.0 include a PostScript map tool for making • Genetic linkage mapping, annotation, Dallas, TX (April 29-May 1, 1996)_ printouts of mouse genetiC maps; an option to view com­ and single-chromosome workshops: Conference hotline: 4071791-0720; posite data sets for recombinant inbred strains; and Elise_Feingold@nihgov electronic registration: 203/379~9427.0 access to Michael Festing's (University of Leicester, U.K.) "Usting of Inbred Strains;' In addition, changes to MGD query forms include a ban­ Chromosome 19 SCW ner at the top of each form providing "buttons" for easier EUCIB Database on WWW navigation within MGD. The Mammalian Homology The European Collaborative Interspecific Interest Sought query form has been redesigned, and the fields "Modifi­ Backcross (EUCIB) provides resources for a Keith Johnson (University of cation Date" and "Accession number" have been added high-resolution genetiC map that will form the Glasgow) would like to hear from to several query forms. Bibliographic records now include basis for constructing a complete physical abstracts, if available, and the Citations query form map of the mouse genome. The MBx data­ anyone interested in participat­ includes an "Abstract" field to search for citations con­ base, which supports the mapping effort by ing in a Chromosome 19 work­ taining specified text in the abstracts. Finally, the Mouse storing mouse, locus, and probe data, is now shop in spring 1996 (+44-1411 Genetic Marker Information query form enables users to available on WWW (http://www.hgmp.mrc. 330-5101, Fax; -4877, gbga98@ specify a ''Type'' of marker or to search by "Cytogenetic ac.uklMBxlMBxHomepage.html).O udcfgla.ac.uk}.O Band" location. 0 12 Human Genome News July-August 1995

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