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Human Genome News Archive Edition

Human Genome News, September 1991; 3(3)

Second International Workshop on Chromosome 3

The Second International Workshop on Human Chromosome 3, sponsored by the DOE Human Genome Program, the NIH National Center for Human Genome Research, and the Eleanor Roosevelt Institute, was held April 4-5 in Denver, Colorado. With 43 participants representing 8 nations, the workshop focused on whole-chromosome resources including probes, polymorphic markers, hybrids, yeast artificial chromosomes (YACs), and genes, and on efforts in genetic linkage and region-specific physical mapping. Two major workshop goals were to identify sets of common reference DNA markers and somatic cell hybrids.

Whole-Chromosome Resources

Cloned DNA markers were described by David Smith (Wayne State University), Harry Drabkin (University of Colorado Health Science Center, Denver), Eugene Zabarovsky (Karolinska Institute, Stockholm, and Engelhart Institute of Molecular Biology, Moscow), Lakshmi Atchison (Fox Chase Cancer Center), and Kazuhiro Yamakawa (Cancer Institute, Tokyo). The total number of clones isolated in their respective laboratories exceeds 12,000, of which about 1400 have been regionally localized.

Localization of DNA markers by fluorescence in situ hybridization analysis was reported by Yamakawa, William Modi (PRI/Dyncorp), and Pamela Rabbitts (Medical Research Council, Cambridge, U.K.).

Somatic cell hybrids useful for localizing DNA markers or isolating specific chromosomal regions were reported by Drabkin, Atchison, Susan Naylor (University of Texas Health Science Center, San Antonio), and Tom Glover (University of Michigan, Ann Arbor).

Isolation of YAC clones specific for chromosome 3 was reported by Mike Mendez (Eleanor Roosevelt Institute). Phyllis McAlpine (University of Manitoba, Winnipeg) described a chromosome 3-specific YAC library.

Manfred Zorn (Lawrence Berkeley Laboratory) demonstrated the Chromosome Information System, which is computer software for entering and storing mapping data.

Genetic Linkage Maps

Polymorphic loci including C-A repeat clones and primer sets for polymerase chain reaction-based allele assays were reported by several groups, including those of Drabkin, Rabbitts, and Naylor.

Several genetic linkage maps with various degrees of coverage were described. The linkage map reported by Yamakawa contained 41 continuously linked markers and extended for a sex-averaged distance of 314 cM. Margaret Pericak-Vance (Duke University Medical Center) and Jonathan Haines (Massachusetts General Hospital) described a 43-loci map that extended 156 cM in males and 203 cM in females. Kalman Tory [NCI-Frederick Cancer Research Facility (FCRF)] reported on a map that included 20 3p loci covering a sex-averaged distance of 130 cM. Vince Stanton (Massachusetts Institute of Technology) described the use of denaturing gradient gel electrophoresis to detect large numbers of polymorphisms for markers that are otherwise noninformative.

Von Hippel-Lindau (VHL) disease (3p25-p26)

Several groups described the current status of linkage between VHL and polymorphic markers on 3p. Using 36 VHL families, Eamonn Maher (Cambridge University, U.K.) found linkage to RAF1 at 6 cM and with D3S18 at 0 cM. Multipoint linkage analysis gave the order CEN-THRB-RAF1-(VHL,D3S18)-D3S191. Berton Zbar (NCI-FCRF) presented data on 41 VHL families and placed VHL between RAF and D3S18 with a marker order of D3S571-RAF-VHL-D3S18-D3S191-D3S627. Zbar also tested these markers for risk determination. Bernd Seizinger (Massachusetts General Hospital) and colleagues found marker order to be RAF1-(c233E2,VHL)-c479H4-c64E2. Several new C-A repeat polymorphisms near VHL were developed, and construction of a long-range restriction map of the VHL region has begun.

3p Syndrome (3p25-pter)

Modi reported on the physical mapping of 15 polymorphic loci near the deletion breakpoint at 3p25.

Small-Cell Lung Carcinoma (SCLC) and Renal Cell Carcinoma (RCC) (3p13-p23)

Data focusing on 3p13-p23, a region commonly found deleted in cancer, was presented by many groups, including Ferenc Boldog (University of Nebraska, Omaha), Charles H.C.M. Buys (University of Groningen, the Netherlands), Drabkin, Bob Gemmill (Eleanor Roosevelt Institute), Gyula Kovacs (NCI-FCRF), York Miller (Veterans Administration Hospital, Denver), Smith, and Yamakawa. The data presented included

  • several hybrid cell lines deleted for specific regions within 3p (Boldog);
  • a study on loss of heterozygosity, which suggested that one putative RCC gene was flanked by D3S2 and THRB (Buys);
  • fine structure mapping of 100 markers into 3p14-p21 and identification of 8 deleted probes in the SCLC cell line U2020 (Drabkin);
  • pulsed-field gel linkage and YAC contigs from within 3p14-p21 including linkage of 7 probes within the U2020 deletion (Gemmill);
  • the loss of 3p sequences and duplication of 5q in RCC (Kovacs);
  • lack of ACY1 expression in many SCLC cell lines (Miller);
  • identification of several potential genes within 3p21.1 and isolation of the t(3;6)(p14.3;p11) breakpoint (Smith); and
  • a study of RCC suggesting that two commonly deleted regions exist at 3p12-14 and 3p21.3 (Yamakawa).


McAlpine placed both TF and PCCB out-side the inversion (distal on 3q), reducing the interval for PCCB to 3q21-q22.

Workshop discussions covered designation of a common reference marker set, common somatic cell hybrids, and a joint YAC screening effort. The DNA markers and somatic cell hybrids are to be deposited with the American Type Culture Collection and the Coriell Institute, respectively. The Drabkin and Gemmill laboratories will seek supplemental funding to permit distribution of purified DNA from these hybrids. A joint YAC screening effort was discussed and received favorable response.

Seizinger will host the next chromosome 3 workshop to be held in Boston in 1992.

A more detailed report of resources and mapping information presented at the workshop will be published in Cytogenetics and Cell Genetics.

Reported by Bob Gemmill, Eleanor Roosevelt Institute

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