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Human Genome News Archive Edition

Human Genome News, November 1990; 2(4)

Chromosome 19 Workshop

The Chromosome 19 Workshop in Charleston, South Carolina, August 3-5, was attended by about 30 scientists from the United States, Canada, and Europe. First drafts of consensus linkage and physical maps were developed. The sessions are described below.

Genetic and Physical Mapping

Myotonic Dystrophy (DM) Research. Robert Korneluk (Children's Hospital of Eastern Ontario) reported that the DM gene is localized to about 1 cM on chromosome 19q. In collaboration with researchers at Lawrence Livermore National Laboratory (LLNL), he successfully used cosmids to "walk" toward the gene. Allen Roses (Duke University Medical Center) briefly described the DM working group, comprising eight institutions in the United States and the United Kingdom. His group is comparing gene expression in the muscles of normal vs DM patients and has located several markers on the distal end of chromosome 19 with a somatic cell hybrid panel. Ann Saunders (Duke University Medical Center) has mapped the comparable DM mouse locus to about an 8 cM region of chromosome 7.

Progress at LLNL. Anthony Carrano described the strategy for long-term physical mapping in which cosmid contigs are created by automated fluorescence-based fingerprinting. Some 60% of chromosome 19 is now covered by cosmid contigs. Gaps are being closed by extension of existing contigs with yeast artificial chromosomes (YACs) or other cosmids. Orientation and between contigs is performed by integration with the genetic map and by fluorescence in situ hybridization. Pieter de Jong discussed the flow-sorted chromosome 19 cosmid library of about 10,000 clones, and Emilio Garcia reviewed the construction of a chromosome 19 YAC library. De Jong described making and extending contigs by using Alu-PCR, in which primer pairs corresponding to Alu repeats are used to help determine the overlap between cosmid clones with similar sequences.

Harvey Mohrenweiser described "seeding contigs," a method of assembling cosmids into contigs using dispersed-middle-repetitive repeat elements, and Anne Olsen explained the assembly of contigs for the carcinoembryonic antigen immunoglobin superfamily locus. Elbert Branscomb detailed the use of relational databases and graphical browsing tools to examine contig data. A mechanism was discussed to allow external users access to these tools.

Progress at Various Laboratories. Keith Johnson (Charing Cross and Westminister Medical School) discussed malignant hyperthermia, which is triggered by inhalation anesthesia. In humans, the gene is probably located near 19q13.2-13.3 and appears to be large. The homologous chromosome in the mouse genome is chromosome 7.

David Saltman (Stanford University School of Medicine) discussed molecular characterization of translocation breakpoints in human leukemia and lymphoma. In acute leukemia patients, genes E2A and lyl-1 are known to exist at translocation breakpoints on 19p. By in situ hybridization, lyl-1 was localized between 19p13.1 and 13.2, and E2A was localized at 19p13.3.

Hubertus Smeets (University Hospital, Nijmegen, the Netherlands) presented a physical map of 19q13 (APOC2-ERCC region) developed using contour-clamped homogeneous electric field gels. Eleven new probes have been mapped in this region of about 2 kb.

Nancy Jenkins (NIH National Cancer Institute) discussed the mouse genetic map, where resolution averages 3 cM. Regions of mouse chromosomes 11, 17, 9, 8, and 7 are homologous to human chromosome 19. Using a rapid new system, this group maps new probes in about 7 days.

Resources and Techniques

Bronya Keats (Louisiana State University Medical Center) described her committee's effort to standardize the presentation of linkage maps, encouraging uniform reporting for each locus mapped. Keats said that there is not enough data yet to develop a framework map of chromosome 19.

James Weber (Marshfield Medical Research Foundation) discussed his polymorphic markers, based on simple sequence repeats (CA or GT), which are very informative, uniformly distributed in the genome, and abundant, occurring about every 10 kb. He has typed 14 markers on the long arm of chromosome 19.

Michael Siciliano (University of Texas M. D. Anderson Cancer Center) described somatic cell hybrids (hamster-human) used for the human chromosome 19 cDNA mapping and DM project. He also reported on work with cDNAs, including a series of four primers used to identify splice donor sites. Using one of them, Siciliano identified the ERCC1 gene sequence in a somatic cell hybrid panel. These polymorphic cDNAs can be used for sequence-tagged sites and can form a database for candidate disease genes. David Brook (Massachusetts Institute of Technology) reported on several radiation-reduction somatic cell hybrid lines and described his "exon trap" to identify genomic DNA.

Need for Future Collaboration

Carrano concluded the meeting by reiterating the need for future collaboration. Workshop participants apportioned responsibility for future projects and agreed to meet once or twice a year, depending on how rapidly new data are generated.

Future Chromosome 19 Projects

  • Finalization of the genetic, physical, and composite maps constructed at the meeting.
  • Construction of a consensus framework contig map from information provided by workshop attendees.
  • Compilation of a list of somatic cell hybrids and mapping panels.
  • Construction of comparative maps of human chromosome 19 and homologous regions in mouse chromosomes.
  • Assembly of data for an STS map.
  • Coordination of the pulsed-field gel mapping data.
  • Development and circulation of guidelines for sharing resources.
  • Publishing of proceedings.

Proceedings will be published in Genomics and on the Human Genome Newsgroup electronic bulletin board. For obtaining access to the newsgroup, see HGN 2(1): 10 (May 1990).

Reported by Bettie J. Graham, Chief
Research Grants Branch
and AnthonyV. Carrano, Director
LLNL Human Genome Center

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Human Genome Project 1990–2003

The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.

Human Genome News

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