LOGY P BIO H YS IC Y S R T S I E T M H E I H C C S E N S G IC IN T E A ER RM ING INFO ISSN: 1050–6101, Issue No. 45 Vol. 10, Nos. 3–4, October 1999 In This Issue HGP Leaders Confirm Accelerated DOE ’99 Oakland Highlights Timetable for Draft Sequence New Sequencing Resources Aid Effort DOE Genome Program Contractors and Grantees Present Progress at the Seventh n September, international leaders be closed and accuracy improved over Meeting, held in January 1999. Iof Human Genome Project (HGP) the following 3 years to achieve a com- Reported by Denise Casey, HGMIS sequencing confirmed a plan to com- plete, high-quality human DNA refer- Introduction ........................1 plete a rough draft of the human ence sequence by 2003 [see HGN Reports on Progress, Challenges .......3 genome by next spring, a year ahead 10(1–2), 1 (www.ornl.gov/hgmis/ Joint Genome Institute .............3 of schedule. This accelerated pace is Sequencing at Other Institutions ......4 publicat/hgn/v10n1/01goals.html)]. So Functional Genomics ..............6 made possible by the commercializa- far, about 13% of human sequence has Informatics.......................8 tion of a new generation of automated been finished, and another 12% is Education and Bioethics ............9 capillary DNA sequencing machines available in draft form (genome.ornl. Microbial Genome Explorations ......9 and by BAC mapping resources gener- gov/GCat; www.ncbi.nlm.nih.gov/ Genome Project ated from DOE-sponsored clone genome/seq). HGP Accelerated Timetable ...........1 projects. HGP Sequencing Progress .........2 Sequencing Allocation Refitting at JGI’s Sequencing Facility . 2 The rough draft will provide a scaffold DOE 2000 Santa Fe Meeting .........10 of sequence across about 90% of the About 60% of the draft sequence will human genome. Remaining gaps will be produced by six major NIH-funded Other Topics (see HGP Timetable, p. 2) In the News Chromosomes 21, 22 Sequence........7 Drosophila Sequence ...............10 Oakland Hosts DOE Genome Program DOE DOE Award Winners ...............11 Human MHC Sequence .............11 Contractor-Grantee Meeting ’99 99 New Mouse Probes .................11 nthusiasm ran high for the DOE sequencing, which remains the major Genetic Testing Advisory Committee ....11 Bioengineering at National Laboratories . .12 EHuman Genome Program (HGP) task facing the HGP today. An over- Public SNP Resource ...............13 in response to impressive gains view of JGI progress begins on p. 3. reported at the Seventh DOE SBIR 1999 Human Genome Awards....13 Investigators representing other HGP- HUGO: London Office, Editors .......15 Contractor-Grantee meeting in Janu- funded projects reported that exciting 1999 Hollaender Winners ............19 ary of this year. Convened every 12 to Protecting Privacy in Research .......19 improvements in mapping and 18 months, this workshop provides an sequencing technologies resulted in Microbial Genomics effective forum for all DOE HGP EcoCyc Database for E. coli ..........14 higher throughput. New approaches to investigators and invited guests to regulating gene expression are helping Microbial Genome News, Resources ...14 discuss their research, initiate col- ELSI News to assess whole-cell effects that are key laborations, and share new material to functional genomics. Attendees Education and Counseling Foundation . 16 resources and software ELSI Resourses ...................16 Meeting ’99 also discussed the applica- capabilities. tion of genome sequencing Informatics Although traditionally Highlights Begin Mouse Genome Informatics 2.2 .......16 information to real-life MRC’s Staden Package .............17 held in Santa Fe, New on p. 3 problems in medicine and Other Resources ..................17 Mexico, the 1999 meeting waste cleanup. DOE is con- was moved to Oakland, California, tinuing activities to educate the gen- Web, Other Resources ...........17,19 so attendees could visit the new Pro- eral public about the HGP and its Calendars .......................18 duction Sequencing Facility of DOE’s societal impact. Researchers in the Funding.........................19 Joint Genome Institute (JGI) in Microbial Genome Program, a spinoff Subscriptions, Acronyms ..........20 nearby Walnut Creek. Two years ago, of HGP, reported impressive gains in JGI began operations under the direc- whole-genome sequencing and analy- HGP Sequencing Progress: p. 2 tion of Elbert Branscomb to address sis, proteomics, and comparative February 2000 Santa Fe Meeting: p. 10 the challenge of high-throughput genomics. Human Genome News issues are placed on the Web soon after going to press. Archived issues are also online. 2 Human Genome News 10(3–4) October 1999 HGP Timetable (from p. 1) sequencing centers, including those Megabase previously established at Washington HGP Sequencing Pairs (Mbp) University, St. Louis; MIT-Whitehead Progress* Institute; and Baylor College of Medi- 3500 cine. In July, laboratories at the Uni- raph at right depicts versity of Washington, Seattle; Gprogress toward generat- 3150 ing a working draft of the Genome Therapeutics Corp.; and 2800 Stanford University joined the NIH human genome by spring 2000 and a complete, high- 2450 production sequencing effort. quality reference human The DOE-funded Joint Genome Insti- DNA sequence by 2003. 2100 tute (JGI) and the Sanger Center Sequences from roughly one- quarter of the human genome 1750 (United Kingdom) will generate about have been deposited into Gen- 10% and 30%, respectively, of the draft Bank (www.ncbi.nlm.nih.gov/ 1400 sequence. (See box, below right, for Genbank), and several indi- details on JGI sequencing.) France, vidual chromosomes are 1050 Germany, and Japan are contributing expected to be completed 700 significant amounts of human before the end of this year. sequence, and China recently joined For updates on HGP sequenc- 350 the worldwide project. To avoid dupli- ing, see Web site (www.ornl. cated work, each laboratory focuses gov/hgmis/project/progress. html). on particular genomic regions (see 379.7 Mbp 426.8 Mbp Human Genome Sequencing Index, *Totals as of September 17, 1999 www.ncbi.nlm.nih.gov/HUGO). Sequencing group members reaffirmed the policy of placing all sequence in JGI Refits Production publicly accessible databases within 24 hours of obtaining a continuous Sequencing Facility 1000- to 2000-base assembly. They ccelerated goals are challeng- also agreed that sequencing should Aing the major Human Genome continue to be based on a proven Project sequencing centers to strategy using BAC clones containing restructure and streamline their DNA from known genomic locations. processes. The Joint Genome Institute (JGI) Production BAC-End Sequences: Sequencing Facility is using 84 Prime Resource new high-throughput MegaBACE DNA sequencing machines acquired from Amersham Pharmacia Biotech. These machines use multiple thin Data from the DOE-funded BAC-end “capillary” tubes instead of large flat gels to separate and “read” the DNA sequencing projects at The Institute sequence. The technology was developed largely with funding from the for Genome Research (TIGR) and the DOE Human Genome Program and licensed to AP Biotech. University of Washington, Seattle (UWS), are critical for achieving the JGI’s current sequencing targets are human chromosomes 5, 16, and 19, new HGP goals. These projects are which together contain about 300 Mb of DNA or about 10% of the entire generating single-sequence reads human genome. Sequencing director Trevor Hawkins reports that as of Sep- from both ends of the human DNA tember 20, JGI had produced 31.2 Mb of finished sequence and about 41 Mb insert in 450,000 BAC clones [HGN of draft sequence (see “HGP Sequencing Progress” box, above). The Genome 10(1–2), 4 (www.ornl.gov/hgmis/ Annotation Consortium is joining with JGI for sequence analysis (see p. 8 publicat/hgn/v10n1/04bacend.html) for details), and Stanford University will be part of the finishing effort.◊ and BAC Web page (www.ornl.gov/ meetings/bacpac)]. valuable tools for eliminating redun- every 3000 to 4000 bases across the In March, DOE increased its support dant sequencing. They can direct entire human genome, a 100-fold of BAC-end sequencing projects to researchers to particular BAC clones improvement over other current accelerate their completion and useful- needed for extending a sequenced human genome maps. Detailed data on ness for guiding production sequenc- region along the chromosome and can BACs are available at TIGR ing. The BAC-end sequences, called identify clones representing genomic (www.tigr.org/tdb/humgen/bac_end_ sequence tag connectors (STCs), are regions still not sequenced. STCs also search/bac_end_intro.html) and UWS can provide quality checks on (www.htsc.washington.edu). The STC sequence assemblies and are useful data resource is complemented by sev- n DOE: $ 89.8M for spanning regions resisting stan- eral other types of mapping informa- FY 1999 HGP n NIH: $ 225.7M dard sequencing biochemistry. tion, including FISH mapping of BAC Budgets clones.◊ n Total: $315.5M STC data will furnish researchers with markers spaced on average October 1999 Human Genome News 10(3–4) 3 DOE DOE Genome Meeting Highlights 99 HGP Grantees Report Progress, Challenges ome 360 researchers, program managers, and invited guests gathered in SCalifornia on January 12–16 for the DOE Human Genome Program work- DOE Sets Next shop. Plenary presentations and posters described a wide spectrum of accom- Genome Meeting plishments and activities, highlights of which are reported below.