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Human Genome News Archive Edition

Human Genome News, September 1991; 3(3)

Second International Workshop on Chromosome 21


The Second International Workshop on Chromosome 21 was held April 10-11 at the Eleanor Roosevelt Institute in Denver, Colorado. The workshop was sponsored by the NIH National Center for Human Genome Research and the DOE Human Genome Program.

Fifty-two investigators from eight countries met to produce a current integrated physical, genetic, and cytogenetic map of chromosome 21 and to determine what is needed to complete the map.

Participants in the Joint Yeast Artificial Chromosome (YAC) Screening Effort, established at the First International Workshop on Chromosome 21 in April 1990 in Bethesda, Maryland, reported that 54 YACs have been isolated and distributed to requesting investigators. Others described the isolation of chromosome 21-specific YACs; Eiichi Soeda (Riken Gene Bank) reported that an additional 17 YACs will be made available after publication.

The following have isolated and mapped chromosome 21-specific YACs in various stages of characterization and availability:

  • Mary Kay McCormick [Los Alamos National Laboratory (LANL)];
  • Marie-Claude Potier [Medical Research Council (MRC) Laboratory of Molecular Biology, U.K.];
  • Joe Gray [formerly Lawrence Livermore National Laboratory (LLNL), now University of California, San Francisco (UCSF)]; and
  • Jeffrey Gingrich [Human Genome Center, Lawrence Berkeley Laboratory (LBL)].

About 20% of the long arm of chromosome 21 is estimated to be represented in YACs.

New Technologies for Chromosome 21 Mapping

Discussions focused on

  • new types of DNA polymorphisms and their use in generating a genetic linkage map [Stylianos Antonarakis (Johns Hopkins University School of Medicine)];
  • microdissection and microcloning to create large numbers (10[6]) of usable chromosome 21 DNA markers and methods for rapidly converting them to YACs or cDNAs [Fa-Ten Kao (Eleanor Roosevelt Institute)]; and
  • two-color fluorescence in situ hybridization for ordering and localizing DNA probes, including YACs (Gray).

Creation of a Chromosome 21 Gene Map

David Cox (UCSF) presented an exon trapping approach to cloning genomic DNA fragments containing coding regions. Michael Siciliano (M.D. Anderson Cancer Center) and Miles Brennan (Mount Sinai School of Medicine) described two approaches to cloning transcribed regions of chromosome 21.

Recent Mapping to Chromosome 21 of Genes Related to Specific Human Diseases

Presentations were made on

  • genetic linkage of a gene responsible for some cases of familial amyotrophic lateral sclerosis to the marker D21S58, located in the 21q22.1 region [Teepu Siddique (Duke University Medical Center)];
  • genetic linkage of a gene coding for progressive myoclonus epilepsy (EPM1) of the Unvericht-Lundborg type to 21q22.3 [Anna-Elina Lehesjoki (University of Helsinki)]; and
  • specific mutation in exon 17 of the amyloid precursor gene in some familial Alzheimer's disease (AD) pedigrees [Mike Mullen (St. Mary's Hospital Medical School, London)]. Because this mutation is not found in all families with linkage of AD to chromosome 21, Jonathan Haines (Massachusetts General Hospital) discussed the possibility of two AD loci on chromosome 21.

Harry Drabkin (University of Colorado and Eleanor Roosevelt Institute) and Misao Ohki (Saitama Cancer Center Research Institute, Japan) each presented the cloning of an 8;21 translocation breakpoint associated with acute myelogenous leukemia. This represents the third chromosome 21 translocation breakpoint detected by physical methods and used as a landmark to relate the physical and cytogenetic maps.

Julie Korenberg (Cedars-Sinai Medical Center) and Jean Delabar (Necker Hospital, Paris) reported on the use of chromosomes from individuals with partial trisomy or partial monosomy; they are also beginning to create a phenotype map in which chromosomal regions defined by the physical map can be associated with specific clinical phenotypes.

Roger Reeves (Johns Hopkins University), Chair of the Committee on Mouse Chromosome 16, and Muriel Davisson (Jackson Laboratory) described progress in mouse genome physical mapping emphasizing mouse chromosome 16; significant homology appears not only between mouse chromosome 16 and human 21 but also between human 21 and mouse chromosomes 10, 17, and perhaps 3.

Manfred Zorn (LBL) presented an update and demonstrations of the LBL Chromosome Information System, including the latest data from the Genome Data Base (GDB) at Johns Hopkins University, made available by Peter Pearson (GDB). Ray Hagstrom (Argonne National Laboratory) demonstrated a Prolog-based alternative for development of a genome database.

A consensus genetic linkage map (1000:1 odds) was constructed at the workshop, using 29 markers from the standard Centre d'Etude du Polymorphisme Humain reference panel and the Venezuelan reference panel. Several new markers included in this map are highly polymorphic polymerase chain reaction markers; most new markers to be added are expected to be this type. Both sources agree on locus order for the common markers; however, in some areas, differences in distance may indicate heterogeneity between the mapping resources. A highly provisional corrected map length of 75 cM (50 cM male and 100 cM female) for the D21S13-CD18 interval was suggested. A current, but highly provisional, combined genetic linkage and physical map of chromosome 21 was also produced at the workshop.

Workshop participants decided to expand FAX on the YACs into a more inclusive chromosome 21 newsletter to disseminate information as rapidly as possible. David Patterson (Eleanor Roosevelt Institute) will serve as editor and be responsible for ordering markers on the physical map. Sue Rider (UCSF) and Rudolph Tanzi (Massachusetts General Hospital) will be responsible for YAC data. Dean Nizetic and Gunther Zehetner (both at Imperial Cancer Research Fund, London) will report on cosmid screening, and Aravinda Chakravarti (University of Pennsylvania) and Antonarakis will assume editorial responsibility for the genetic linkage map aspects of the newsletter. Antonarakis was chosen to organize the next chromosome 21 workshop.


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


Reported by David Patterson, Eleanor Roosevelt Institute

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