The Jackson Laboratory partnering in international mouse sequencing project
| Date: December 17, 2008 |
The U.K.-based Medical Research Council and Juvenile Diabetes Research Foundation have launched a $4.4 million project, involving The Jackson Laboratory and research institutions in the U.K. and Europe, to sequence the genomes of the 17 most widely used strains of laboratory mouse.
The three-year project will use next-generation sequencing technologies to produce detailed sequences for each of the strains. The DNA sequences will help to identify and characterize many human disease-related genes, and will be made openly available to the research community.
Dr. David Adams, investigator at the Wellcome Trust Sanger Institute, who will lead the project, says: "This award is a great boost for researchers around the world working to understand the genetic components of disease. We have already carried out pilot studies to guide our approach and can now move forward swiftly to deliver these new resources."
More than 400 genetically defined strains are available to the worldwide scientific community from The Jackson Laboratory and other sources, but the vast majority of researchers study a much smaller subset of 17 strains.
Jackson Laboratory Professor Gary Churchill advised the team on the selection of mouse strains for the project, and in particular recommended the inclusion of eight highly diverse genetic strains that are the founders of the collaborative cross (CC). "The CC is an ongoing breeding effort to develop several hundred new strains of mice for genetics research," Dr. Churchill explains. "With complete genomic sequence of the CC founder strains and high-density array genotyping, it will be possible to impute the complete genomes of the CC strains and tens of thousands of genomes that can be generated from them. Leveraging the sequence data from the Sanger project in this way will provide a test bed for predictive genetics in humans based on whole-genome sequence data."
Within the next 18 months, the team will use next-generation sequencing technologies to produce draft sequences of each of the 17 strains. In order to maximize the benefits of this work, the draft sequences will be freely released to the research community through the Ensembl genome browser. Once these draft sequences are complete the team will then move towards a final draft of each strain.
Research groups around the world that use these strains will be able to move quickly from knowledge of the often large genomic regions that contribute to variation to precise analysis of specific variants. The genome sequences will help them to home in on the gene or genes of interest, spending less time on finding the variant and more time and resources understanding the biological mechanisms.
"Mouse strains differ from each other in a wide range of medically important characteristics, and these differences are a result of complex genetic variations between them," says Professor Ian Jackson, senior scientist at the MRC Human Genetics Unit in Edinburgh. "By obtaining the complete genome sequences of each strain, we can identify all these genetic differences and these will allow us to discover the fundamental biological processes that result in these models of common human disease. The new sequencing technologies now allow us to deliver this sequence quickly and at a reasonable cost."
The team has already carried out a pilot to guide this major effort, producing sequences from a region of mouse chromosome 17 that contains many of the genes involved in the immune system. These results reveal the amount of sequence data they must generate in order to provide high-quality genomes to the community.
Capitalizing on complementary skills, the new program is a collaboration between the Wellcome Trust Sanger Institute, MRC Mammalian Genetics Unit (Harwell), MRC Human Genetics Unit (Edinburgh), the Wellcome Trust Centre for Human Genetics (Oxford), the European Bioinformatics Institute and The Jackson Laboratory in Bar Harbor, Maine. An international scientific advisory board of leading mouse researchers will also support this project.
Once the first draft of the human genome sequence was completed In 2000, the scientific world agreed that the next sequencing project should be the laboratory mouse, as the premier research model to study human disease and normal development. Two years later, a public-private research consortium published a draft sequence for the world's most widely used laboratory mouse strain; the mouse in question was a female C57/BL6J mouse from The Jackson Laboratory.
The Jackson Laboratory is an independent, nonprofit biomedical research institution and National Cancer Institute-designated Cancer Center based in Bar Harbor, Maine, U.S.A., with a facility in Sacramento, California. Its mission is to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the global biomedical community. The Laboratory is the world's source for more than 4,000 strains of genetically defined mice, is home of the mouse genome database and is an international hub for scientific courses, conferences, training and education.
Juvenile Diabetes Research Foundation is the largest charitable funder and advocate of type 1 diabetes research. The mission of JDRF is to find a cure for diabetes and its complications through the support of research. Since its founding in 1970 by parents of children with type 1 diabetes, JDRF has awarded more than $1.3 billion to diabetes research, including more than $156 million in FY2008, when the Foundation funded more than 1,000 centers, grants and fellowships in 22 countries.
The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992 as the focus for UK sequencing efforts. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms such as mouse and zebrafish, and more than 90 pathogen genomes. In October 2005, new funding was awarded by the Wellcome Trust to enable the Institute to build on its world-class scientific achievements and exploit the wealth of genome data now available to answer important questions about health and disease. These programmes are built around a Faculty of more than 30 senior researchers. The Wellcome Trust Sanger Institute is based in Hinxton, Cambridge, UK.
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