"The mouse plays a vital role in research on human biology and disease," says John D. McPherson, Ph.D., associate professor of genetics and the lead investigator on the St. Louis team. "This physical map gives us the big picture of the mouse genome. It will be tremendously helpful to medical investigators and to those studying the human genome."
Comparison of the mouse and human maps, for example, can highlight regions of DNA that control genes. These regions are crucial to understanding the role of genes in health and disease, but they are difficult to find using current methods.
The physical mouse-genome map is a complementary effort to the draft sequence of the mouse genome, which was released last May. The important difference is one of detail and organization, says McPherson.
The draft sequence is a description of the chemical bases--represented by A, C, G, and T--that make up the genome. The physical map organizes and delineates this information on the mouse's 20 chromosomes. McPherson compared the draft sequence to loose pages from an encyclopedia. The pages may provide a lot of information, but they lack context.
"Each page may provide many details," he says, "like the population and climate of a country. But until all the pages are assembled correctly, you may not know that you are reading about Zaire." A physical map places all the "pages" of DNA sequence in their correct order within each volume, with each volume being a chromosome.
Furthermore, the DNA-sequence information used to compile the physical map was gathered differently from the information used to compile the draft sequence. Because the physical map comes from a separate source of genetic information, the researchers are using it to confirm the accuracy of the draft sequence.
"We are comparing the two independent data sets to be certain they are giving us the same answer," says McPherson.
The physical map benefits medical researchers in another way, as well. It was assembled using longer segments of DNA than those used to assemble the draft sequence. The long segments were grown, or cloned, in bacteria. Now that the mapping is complete, the bacteria containing these bits of mouse genome continue to be grown, stored in freezers, and carefully cataloged. Investigators studying mouse genes or regions of DNA now can locate the location of that particular segment on the map and obtain the actual clone of that region to study, rather than isolating the region themselves.
The following centers contributed to the project:
The Wellcome Trust Sanger Institute, Hinxton, Cambridge, England (http://www.sanger.ac.uk)
Genome Sequencing Center, Washington University School of Medicine, St Louis (http://genome.wustl.edu/)
Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada (http://www.bcgsc.bc.ca/)
The Institute for Genome Research, Rockville, MD (http://www.tigr.org/)
Children's Hospital Oakland Research Institute, Oakland, CA (http://www.childrenshospitaloakland.org/)
EMBL--European Bioinformatics Institute, Hinxton, Cambridge, UK (http://www.ebi.ac.uk)
Department of Electrical Engineering, Washington University, St Louis (http://www.ee.washington.edu/)
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.
A physical map of the mouse genome. http://www.nature.com or http://dx.doi.org/10.1038/nature00957 (Nature subscribers can view the full text; all others can view the abstract).
Funding from the Wellcome Trust and the National Institutes of Health supported this research.
Journal
Nature