Maps Of Mice - And Men
A UK-US-Canada consortium coordinated at the Wellcome Trust Sanger Institute publishes in Nature online (Sunday, August 4, 2002, 19.00 GMT) the most comprehensive map of the mouse genome, containing an estimated 98% of the DNA sequence. The map has already proven a valuable resource in the hunt for mouse and – even more importantly – human genes.
The genome of the mouse is widely regarded as one of the keys to understanding the human genome sequence. For example, comparing the two sequences can highlight regions that act to control genes. Such control regions, which are very difficult to find using current methods, are crucial in understanding the role of genes in health and disease. An accurately ‘drawn’ mouse genome map is vital in helping to turn human DNA sequence into a research tool for biomedicine.
The mouse map resembles an atlas of a country: it provides an overview of the genome landscape and, because all locations are indexed, it allows the user to focus rapidly on the region of interest. Any ‘page’ of the mouse genome can be selected and any piece of information – or any remaining uncertainty or problem in the sequence – can be examined by concentrating the effort exclusively on the relevant place, while excluding all the other parts.
“By investing in a large-scale collaborative effort, we have been able to generate an exceptional resource that covers almost 100% of the mouse genome. The map allows us to pick out the regions that are lacking in the whole genome assembly, to focus on genes and to highlight regions of similarity between mouse and human.”
Simon Gregory Leader of the project at the Wellcome Trust Sanger Institute
Without a map, it is not possible with current technology to sequence a large genome finished to the standards demanded by the international research community. All large genomes are finished using mapped DNA clones.
“As we move forward to interpreting the code of life, the Wellcome Trust Sanger Institute will provide a suite of resources that will accelerate discovery by biomedical researchers around the world. The map of the mouse genome is one example of the collaborative work we and our partners do to put enabling research tools as swiftly as possible into the hands of those who need them – scientists working to understand and defeat disease.”
Professor Allan Bradley Director of the Wellcome Trust Sanger Institute
In the two-year project more than 300,000 randomly selected individual genomic fragments were overlapped to establish unlocalized coverage of the mouse genome – fewer than 8000 genome segments. In a final mapping step, unique mouse chromosome data were incorporated to reduce that number still further: the published map contains fewer than 300 gaps.
“The publication of the mouse physical map represents a major milestone in our study of the function of genes in both human and mouse. Together with the mouse draft sequence, it is transforming the science of mouse genetics and will enormously enhance our ability to understand the role of genes in human disease.”
Professor Steve Brown Director of the MRC Mammalian Genetics Unit, Harwell, one of the largest mouse genetics research centres in Europe
The map will continue to be improved and developed. The value of the publication also lies in the way in which the methods developed for this project can be exploited in the future. The laboratories involved have been at the forefront of exploring technologies to provide genomic information as rapidly as possible and the mouse map is a benchmark for future work.
Very rapidly and with little DNA sequencing a biological repository can be produced for a species that allows researchers to home in on the regions of the genome that interest them and provides the materials to take biomedical research forward.
“The mouse is one of the most important animal models for studying cancer and many other human diseases. Rapid and accurate mapping of the mouse genome and linking the map to the human genome sequence will accelerate world-wide efforts to understand the molecular basis of cancer, and will provide an important genomic resource for the international research community.”
Dr Marco A. Marra Director of the Genome Sciences Centre in Vancouver
In comparative genomics, new sets of information for each species are being used to improve analysis and accuracy of existing sequence sets. A major role of genomics and bioinformatics is to manage and exploit these large datasets through collaborative work and exchange.
More information
Publication
The mouse map report is published first as an Advance Online Publication (AOP) on http://www.nature.com/nature/ at 19.00 London time/14.00 US Eastern time on Sunday, August 4, 2002.
The paper version of the paper is Nature 418, 743 – 750 (2002); doi:10.1038/nature00957
Additional Quotes
John McPherson, Associate Professor of Genetics at Washington University, added: “We have been able to build upon the experience of constructing a clone-based map of the human genome. This accelerated the construction of the mouse map providing a tremendous resource for the mouse scientific community. The physical map will continue to be curated and be made publicly available.”
Dr David Bentley, Head of Human Genetics at the Wellcome Trust Sanger Institute, added: “One of the key features of this project was using the human genome sequence to accelerate the process of mapping out the mouse genome. The enormous success of this approach points the way for tackling many other mammalian genomes.”
Pieter de Jong, Director of BACPAC Resources at the Children’s Hospital & Research Center at Oakland expressed his excitement: “It is very gratifying that this new mapping approach will open the floodgates towards similar studies for many additional species relevant for human health and the human food supply. Species such as rat, cat, dog, cattle, pig and chicken are already available to the international community through the unique cloned genomic fragment resources created in Oakland”
Participating Centres
The Centres that contributed to the project are:
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The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
The Wellcome Trust Sanger Institute was founded in 1992 as the focus for the UK sequencing effort of the human genome: the Institute is responsible for the completion of the sequence of approximately one-third of the human genome, The Institute is also a major contributor to the mapping and sequencing of the mouse genome, the zebrafish genome and genomes of a range of pathogens.
The Wellcome Trust is an independent research funding charity, established under the will of Sir Henry Wellcome in 1936. It is funded from a private endowment which is managed with long-term stability and growth in mind. The Trust’s mission is to foster and promote research with the aim of improving human and animal health.
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Genome Sequencing Center, Washington University School of Medicine, St Louis, MO, USA
The Genome Sequencing Center (GSC) at Washington University School of Medicine in St. Louis focuses on the large scale generation and analysis of DNA sequence. Founded in 1993, the GSC is one of the top sequencing centers in the United States. The GSC played a leadership role in the International Human Genome Project and was a major contributor to mapping and sequencing the mouse genome.
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Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada
The British Columbia Cancer Agency Genome Sciences Centre (Vancouver, Canada), with support from the BC Cancer Foundation, is focused on the application of genomic technologies to cancer research. The Genome Sciences Centre, a leader in the generation of BAC fingerprint maps, has placed special emphasis on bioinformatics, genome mapping, gene expression profiling and DNA sequencing, applying these tools to unravel the molecular basis of cancer and other diseases.
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The Institute for Genomic Research, Rockville, MD, USA
The Institute for Genomic Research (TIGR) in Rockville, Maryland, is a not-for-profit research institute which conducts structural, functional and comparative analysis of genomes and gene products from a wide variety of organisms, including viruses, eubacteria, archaea, and eukaryotes.
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Children’s Hospital & Research Center at Oakland, Oakland, CA, USA
Children’s Hospital & Research Center at Oakland is a nonprofit, independent hospital founded in 1912, and is the largest and busiest pediatric facility between Los Angeles and Seattle. Children’s Hospital Oakland Research Institute (CHORI) is the research arm of the hospital and is one of the nation’s top ten pediatric research facilities. CHORI’s 200-plus basic and clinical researchers strive for fundamental advances in both the basic and applied biomedical sciences, and work to promote the hospital’s mission to deliver extraordinary care for all children.
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EMBL-European Bioinformatics Institute, Hinxton, Cambridge, UK
EMBL-EBI The European Bioinformatics Institute is a non-profit academic organisation that forms part of the European Molecular Biology Laboratory (EMBL). EMBL’s main Laboratory is in Heidelberg, Germany, and serves as headquarters for an international network of research institutes funded by contributions from sixteen countries. The roots of the EBI lie in the EMBL Nucleotide Sequence Data Library, which was established in 1980 at the EMBL laboratories in Heidelberg, Germany and was the world’s first nucleotide sequence database. In September 1995 the EBI moved to its current location on the Wellcome Trust Genome Campus. The mission of the EBI is to ensure that the growing body of information from molecular biology and genome research is placed in the public domain and is accessible freely to all facets of the scientific community in ways that promote scientific progress.
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Department of Electrical Engineering, Washington University, St Louis, MO, USA
Internet resources
The mouse map has been released, as it has been developed, through the following websites:
