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Human Genome News Archive Edition

Human Genome News, May 1991; 3(1)

Nonprofit Resource Centers Facilitate Mapping

Investigators in the international Human Genome Project and others often rely on centralized sources of cell lines and DNA to facilitate mapping. For nominal fees, these nonprofit sources offer reliable, well-characterized cell cultures and DNA samples that enable comparison of results from different laboratories. In addition, individual laboratories are spared costly and timeconsuming storage and distribution and are given access to the latest resources.

Repository services include collection, authentication, amplification, storage, and distribution of cells and DNA, including management of updated information on all holdings. Several repositories also maintain databases on results obtained using their resources. Access to some of the resources may be limited.

U.S. Centers

Two major U.S. resource centers are the American Type Culture Collection (ATCC) in Rockville, Maryland, and the Coriell Institute for Medical Research in Camden, New Jersey. ATCC, a private, nonprofit organization, maintains the most diverse existing collection of microorganisms and cell lines, including bacteria, fungi, protozoa, viruses, metazoan cell lines, and DNA recombinants. Coriell houses the world's largest collection of human cells and offers somatic cell hybrid resources.

Other important resource facilities include the National Cell Culture Center and the Jackson Laboratory. The newly established National Cell Culture Center in Minneapolis, Minnesota, provides large-scale mammalian cell culture services. Jackson Laboratory, located in Bar Harbor, Maine, offers mouse strains, mutations, and mouse DNA resources.

These centers are under contract to various federal agencies to provide resources to or serve as repositories for the research community.

ATCC

Since 1925 ATCC has maintained and distributed biological resource material to the international research community. It offers the following traditional material:

  • 13,630 bacterial strains,
  • 24,780 strains of filamentous fungi and yeasts,
  • 1005 protozoan type cultures,
  • 1485 animal and plant viruses, and
  • over 3000 human and other animal cell cultures.

ATCC recently added a collection of recombinant DNA probes, clones, and libraries; approximately 400 new probes and 5 to 10 new libraries will be added annually. A description of several useful ATCC mapping resources follows.

DNA Probes and Libraries Repository

In 1985 the NIH National Institute of Child Health and Human Development (NICHD) established an international Repository of Human and Mouse DNA Probes and Libraries within ATCC. Repository functions include the following activities:

1. DNA Probes; Clone and Genomic Collections. Repository staff obtain, amplify, and distribute over 100 probes detecting restriction fragment length polymorphisms (RFLPs). They also maintain clone and genomic repositories from known genes independent of RFLP detection.

  • The clone repository-over 1640 human and 155 mouse clones-contains discrete sequences distributed throughout the human and mouse genomes. Clones specific to each human chromosome and most mouse chromosomes are available. Restriction analysis is used to verify the structure of all clones received. A photograph of the ATCC restriction digest gel and a sample of the ATCC clone preparation are returned to the depositor for confirmation before the clone is distributed as transformed bacteria or bacteriophage. Clones with human inserts may also be available as purified DNA. The NICHD contract mandates that 300 human and 100 mouse clones be added annually.
  • The genomic repository was established in 1988 to maintain a collection of clones constituting a complete genome. Its primary function is to develop and evaluate methods and instrumentation needed to maintain a human genome repository. These methods include automated DNA preparation; clone verification; data maintenance and analysis; and sample storage, recovery, and distribution. Currently available are 850 clones from the Saccharomyces cerevisiae genome (provided by Maynard Olson's Washington University Laboratory), organized in about 180 different contigs.

2. National Laboratory Gene Library Project (NLGLP) Resources. Sixty chromosome-specific gene libraries constructed at Lawrence Livermore National Laboratory (LLNL) and Los Alamos National Laboratory (LANL) are preserved and distributed by ATCC. [HGN 2(1), 12-13 (May 1990)].

3. Information Management/Database. Catalogues, information sheets, and a menu-driven online database describe the repository's holdings. For information on database access, see ATCC Repository Database Access.

4. DNA Primers. ATCC offers predesigned oligonucleotide primers for in vitro amplification of human DNA, including oligonucleotide pairs for 50 polymorphic loci. Product sheets give information on primers, including allele sizes, gene name, cytogenetic location, and sequence.

Other ATCC Mapping Resources

ATCC offers over 3000 well-characterized cell lines and hybridomas through five different government-sponsored collections, thus providing a valuable resource for studying gene expression. About 80 species are represented, with the majority of cultures being human, lower primate, or laboratory animal in origin. [Contact: Technical Collection Specialist, 301/231-5553.]

Coriell Institute for Medical Research

Located on the campus of the University of Medicine and Dentistry of New Jersey, the Coriell Institute is a nonprofit biomedical research institute that establishes, characterizes, stores, and distributes over 7000 cell lines worldwide. Coriell has provided cells to scientists around the world for 18 years and in 1990 began offering DNA samples.

Three major NIH cell repositories housed at Coriell compose the world's largest collection of human cells:

  • Human Genetic Mutant Cell Repository of the National Institute of General Medical Sciences, founded in 1972;
  • Aging Cell Repository of the National Institute on Aging, created in 1974; and
  • National Cell Repository (NCR) of the National Institute of Mental Health. Established in 1990, NCR facilitates research on the genetic components of manic depression, Alzheimer's disease, and schizophrenia. This repository is expected to add 6000 cell lines by 1993 and to achieve a total of 7500 additional lines by 1995.

The three repositories above, in addition to smaller collections on cancer, diabetes, and other diseases, are collectively known as the John T. Dorrance, Jr., International Cell Science Center. Richard Mulivor is the director.

Cell Lines. All cell lines, which are derived from samples collected worldwide, are screened to confirm species of origin and for mycoplasmas and other contaminants, are well characterized, and are clinically documented. An extensive bibliographic database and abstracts of literature citations documenting culture characterizations are also maintained.

Human Cultures. Coriell maintains cell cultures (derived from human fibroblasts, lymphoblasts, and amniotic fluid) that represent over 400 genetic diseases and 800 chromosomal aberrations. Virus-transformed fibroblast cultures and cultures from apparently normal individuals are also available.

To aid linkage analysis studies, Coriell offers cultures from multigenerational family groups; databases are being maintained by several contributors of samples. Within the collections are samples from affected individuals and families (including nonaffected members) with cystic fibrosis, fragile X-linked mental retardation, Huntington's disease (from the Venezuelan pedigree), retinitis pigmentosa, and major affective disorder (from the Amish pedigree). Utah pedigrees were contributed by Ray White and collaborators at the Howard Hughes Medical Institute (HHMI) in Utah.

Somatic Cell Hybrids: Cultures and DNA. Human/rodent somatic cell hybrids are available as cultures nd purified DNA. For details on their mapping panel, see box. Coriell also offers DNA from monochromosomal hybrids for human chromosomes 2-9, 11-14, 16-19, 21, 22, X, and Y, as well as DNA from hybrids retaining 3 or fewer human chromosomes in a variety of combinations.

[Contact for Coriell collections: Richard Mulivor, 609/757-9697. Catalogue: 800/752-3805 or 609/757-4848, Fax: 609/964-0254.]

National Cell Culture Center

The National Cell Culture Center offers customized services for large-quantity production of animal cells and secreted proteins. By providing access to state-of-the-art cell culture instrumentation and techniques, this new program addresses the needs of the small research laboratory as well as those of larger collaborative groups. The center provides cells in suspension and monolayer cultures in quantities ranging from 25 to 150 L. In addition, cell-secreted products such as monoclonal antibodies are available in quantities of 1 to 100 g.

Sponsored by NIH National Center for Research Resources, this service is available to researchers throughout the United States and Canada. The Scientific Advisory Committee selects and prioritizes requests; preference is given to NIH-supported projects. Researchers are charged only for consumable materials and a portion of labor costs for each project. [Application form or additional information: Mark Hirschel, director, 800/325-1112, Fax: 612/786-0915.]

Jackson Laboratory

Located in Bar Harbor, Maine, Jackson Laboratory maintains a widely diverse collection of genetically defined mice for basic research and for studies of genetic and developmental factors underlying a variety of disorders. Over 700 different mutations and 1000 different strains and sets of recombinant inbred strains and congenic strains are regularly used for mapping studies by scientists worldwide. These are available through the laboratory's Foundation and Special Mouse Stocks, Mouse Mutant Resource, and Robertsonian Chromosome Resource.

The Mouse DNA Resource offers genomic DNA (from splenic extracts) from inbred, congenic, and mutant-bearing mouse strains. [Contact: Marie Ivey, 207/288-3371, ext. 1395.]

The Genetic Information Resource compiles and distributes information on the laboratory's numerous mouse strains and mutants (e.g., genetic linkage data that can be visualized directly or on chromosome maps), specific gene typing for given strains, literature references, and phenotypic characteristics of strains. In addition, the GBASE database maintains information about mouse loci, allelic characterization of inbred strains, and genetic maps.

International Centers

U.K. DNA Probe Bank

Funded by the Medical Research Council as part of the U.K. Human Genome Mapping Project Resource Centre, the probe bank offers some 650 DNA probes free to the U.K. research community. Foreign investigators may be subject to fees and restricted access (HGN 2(6), 1-3 (March 1991)]. [Contact: Christine Bates, (Int.) 44/81-869-3446, Fax: (Int.) 44/81-869-3807.]

European Cell Bank

The European Cell Bank consists of two components serving gene mappers in the United Kingdom and Europe:

  • European Collection of Animal Cell Cultures Human Cell Bank, housed at the Public Health Laboratory Service (PHLS) at Porton (United Kingdom), prepares and distributes lymphoblastoid and other cell lines. Many lines have constitutional chromosomal rearrangements with breakpoints useful for human gene mapping. Foreign investigators may have restricted access to some materials. [Contact: B. Bolton, PHLS Centre for Applied Microbiology and Research, (Int.) 44/0980-610391, Fax: (Int.) 44/0980-611315.]
  • Department of Cell Biology and Genetics at Erasmus University (Rotterdam) banks fibroblast lines, with particular emphasis on inborn errors of metabolism. [Contact: V. Cleijer, (Int.) 31/10-408-7223, Fax: (Int.) 31/10-408-7200.]

Centre d'Etude du Polymorphisme Humain (CEPH)

The mission of CEPH, established in Paris in 1983 as a nonprofit institution, is to facilitate construction of human genetic linkage maps of each chromosome by using DNA polymorphisms. CEPH coordinates international gene-mapping efforts for collaborating researchers in laboratories in North America, Europe, South Africa, Japan, and Australia.

Reference Panel. The main premise of CEPH is that collaborative research on DNA from the same families will result in earlier completion of the human genetic linkage map. CEPH provides its collaborators with free, high-quality cellular DNA samples from a panel consisting of DNA from 40 large families (each with at least 6 children) with no known genetic diseases. Collaborators use their own probe and restriction enzyme combinations to determine the genotypes of various DNA polymorphisms for the entire panel. All data are sent to the CEPH database.

Database. The CEPH database, containing genotypes for all tested genetic markers (mostly DNA polymorphisms), consists of a collaborative portion and a public portion. The collaborative database, available only to CEPH investigators, includes unpublished and published data. Published data are later moved to the CEPH public database (available to the general scientific community). Unpublished data can be released to the public database after 2 years. [To receive the database, available on a 5.25-in. disk, and a book of LOD scores and recombination-frequency estimates for syntenic markers in the database, write to CEPH; 27 rue Juliette Dodu; 75010 Paris, France.]

Consortium Linkage Maps. CEPH investigators construct consortium maps of each chromosome, using published data from the database. The first such map, of chromosome 10, was recently published [Genomics 6, 393-412 (1990)] with a mean distance of 11 cM between genetic markers. The second consortium map, of chromosome 1, was published in April [Genomics 9, 686-700 (1991)] with a mean genetic distance of 6.7 cM. To provide resources for constructing higher-resolution maps (perhaps 1 to 2 cM), CEPH is enlarging its reference panel to include 61 families.

Probe Collections. A project being developed in collaboration with ATCC is the construction of probe kits for the mapped genetic markers on CEPH consortium maps. Sponsored by NIH National Center for Research Resources, this project aims to enhance the use of the CEPH consortium genetic linkage map by enabling researchers to localize disease-determining and other interesting genes.

[Contact for CEPH: Howard Cann, Fax: (Int.) 33/1-40-18-01-55 (Paris).]

Japanese Cancer Research Resources Bank

The Japanese Cancer Research Resources Bank, established to facilitate cancer research, includes cell and gene repositories. Resources are available to qualified investigators associated with certain medical, research, or educational organizations. [Contact: Katsuyuki Hashimoto; Gene Repository Section; National Institute of Health; 10-35, Kamiosaki 2-Chome; Shinagawa-ku, Tokyo 141; (Int.) 81/03-444-2181, ext. 304, Fax: (Int.) 81/03-446-6286.]


ATCC Catalogue

The fourth edition of the ATCC/NIH Repository Catalogue of Human and Mouse DNA Probes and Libraries (1990) lists materials deposited at ATCC as part of the DNA repository. Also enumerated are related materials from the ATCC molecular biology collection and Patent Culture Depository.

Contact for catalogue:

  • 800/638-6597 or 301/881-2600
    Fax: 301/321-5826

Repository information:

  • Donna Maglott, 301/231-5586
    Fax: 301/770-1541

Reported by Denise Casey
HGMIS, ORNL

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Human Genome Program, U.S. Department of Energy, Human Genome News (v3n1).

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

Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.