Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, July 1991; 3(2)
Thirty-six scientists from the United States, the United Kingdom, and Australia attended a workshop on chromosome 17 in Park City, Utah, on March 15-16. The workshop was sponsored by NIH and the U.K. Medical Research Council to compile chromosome 17 mapping and resource information and to coordinate sequence tagged site (STS) development and yeast artificial chromosome (YAC) screening efforts.
Genetic mapping data were presented for over 200 polymorphic markers. Pamela Fain and David Barker (University of Utah) presented a framework map that included 32 uniquely ordered markers (1000:1 odds). Peter O'Connell, Rose Plaetke, and Ray White (University of Utah and Howard Hughes Medical Institute) reported a framework map of 40 markers, 13 of which were common to the two maps. A total of 17 markers met the heterozygosity criteria for index markers (over 70%).
Fain and Richard Kouri (BIOS Corporation) have constructed crossover maps for all meioses in 40 Centre d'Etude du Polymorphisme Humain (CEPH) reference families in preparation for high-resolution genetic mapping using meiotic mapping panels.
David Ledbetter (Baylor College of Medicine) described two YAC contigs in the Miller-Dieker lissencephaly syndrome region (MDS; 17p13.3). Several researchers agreed on a consensus localization of CMT1 (Charcot-Marie-Tooth disease locus) to a 6- to 10-cM interval in 17p11.2, distal to SMCR (Smith-Magenis syndrome locus) and markers D17S71 and D17S122 and proximal to markers D17S124 and D17S460. They were Philip Chance (University of Utah School of Medicine), Kelian Chen and Kenneth Fischbeck (University of Pennsylvania School of Medicine), Roger Lebo (University of California, San Francisco), Pragna Patel (Baylor College of Medicine), David Ross (University of Sydney, Australia), Charles Schwartz (Greenwood Genetics Center), and Jeff Vance (Duke University Medical Center).
In other reports, Kenneth Kidd (Yale University) described a 140-kb cosmid contig of a homeobox (HOX2) region and an 80-kb contig around the nerve growth factor receptor locus (NGFR). Ellen Solomon [Imperial Cancer Research Fund (ICRF)] related that several groups in the breast cancer consortium have confirmed genetic linkage between early-onset breast cancer and D17S74 in a subset of early-onset families. Jeff Hall (University of California) presented linkage data suggesting that a cancer-predisposing gene is distal to D17S74.
A somatic cell hybrid panel developed by Ledbetter and coworkers has been deposited in the Human Genetic Mutant Cell Repository at the Coriell Institute in Camden, New Jersey. The panel consists of a chromosome 17-only hybrid and ten translocation or deletion breakpoints that divide the chromosome into ten intervals.
Four other somatic cell hybrid panels are available for chromosome 17, including chromosome-mediated gene transfer hybrids and radiation hybrids reported by Solomon and microcell hybrids and radiation hybrids reported by Robin Leach (University of Texas). Participants agreed that testing a common set of markers against all hybrids is essential to constructing a composite breakpoint map.
Sixty-two STSs are available for chromosome 17, including 40 from cloned genes, 7 from C-A repeats or other highly polymorphic loci, and 15 from other anonymous DNA markers. Participants agreed to avoid duplication of effort by sharing their plans to develop STSs and other freely available probes for reference markers.
principles and policies for a joint yac screening effort were discussed. groups at the university of michigan (17q) and baylor college of medicine (17p) will perform initial screening using the washington university yac library, which will be merged with a chromosome 17 set of 36 yacs from leiden university and the university of pennsylvania. an advisory committee was appointed to monitor the screening effort.
Two other YAC libraries currently being developed for screening chromosome 17-specific sequences include the CEPH YAC library by White and Hans Albertsen at the University of Utah and a new YAC library by Tony Monaco and Hans Lehrach at ICRF in London.
A flow-sorted chromosome 17 cosmid library constructed by Dean Nizetic (ICRF) and Lehrach has been arrayed and stamped onto 2 high-density filters, each containing 10,000 cosmid clones. A general policy statement for use of these filters was distributed for comments and amendments. An array of cosmids made from flow-sorted material has also been prepared at Los Alamos National Laboratory.
Participants agreed that all materials and resources presented at past and future workshops would be accessible to group members within 6 months of the workshop. YACs identified through the joint screening effort will be available immediately to all participants who contribute markers. A database and communication system for distributing information relating to the status of STS production and YAC screening will be developed during the coming year.
A more detailed report of resources and mapping information presented at the workshop will be published in Cytogenetics and Cell Genetics.
Chromosome 17 contact:
Reported by Pamela Fain
University of Utah
Salt Lake City, Utah
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Human Genome Program, U.S. Department of Energy, Human Genome News (v3n2).
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