May 18, 2001
In only six months, the Mouse Sequencing Consortium (MSC), an international public-private effort to accelerate the sequencing of the mouse genome, has generated enough DNA data to cover the mouse genome three times.
The consortium estimates that the sequence data represents at least 95 percent of the total complement of mouse DNA, and they are making the data freely available to researchers around the world.
"Through academia-industry cooperation, we have been able to create a resource in just a few months that will speed discovery in both mouse and human research. The data is out there for all to use," said Robert H. Waterston, M.D., Ph.D, the James S. McDonnell Professor and head of the Department of Genetics, professor of anatomy and neurobiology, and director of the Genome Sequencing Center at the School of Medicine.
The center is one of three DNA sequencing laboratories involved in the MSC project.
All mammals, including humans and mice, are believed to share a common ancestor that lived millions of years ago. As a result, the genomes of mammals have many similarities. The most important functional regions of the genome --the genes that contain the information to make proteins --have undergone relatively small changes. Any changes that interfere with essential functioning probably would not be passed on to the next generation. Some genes shared by mice and humans have changed so little that they remain 90 percent similar.
Meanwhile, the regions of the genome that don't make proteins --the so-called non-coding regions of DNA --are much less similar from mouse to human. By comparing the mouse genome sequence to the human sequence, the similar regions can be recognized, and using computers to do comparisons, scientists are able to find these regions of similarity. Many of these regions contain previously unrecognized genes.
In addition, by comparing mouse DNA with human DNA, scientists should be able to find other functionally important features of the human genome that have been conserved, such as regulatory regions of DNA that turn genes on and off.
"The mouse DNA sequence is an important tool for finding genes in the human," said Francis S. Collins, M.D., Ph.D., director of the National Human Genome Research Institute. "Comparing mouse sequence to human sequence will help identify previously unknown human genes, in essence using evolution's 'lab notebook' to understand how the genome works. We need to finish the work so the mouse sequence is as accurate and complete as the human sequence."
The MSC used a whole genome shotgun approach to quickly generate initial coverage of the genome. The next step will be to provide greater depth of coverage. The MSC scientists will use larger stretches of DNA of known map position and will assemble the fragmentary pieces of DNA into the finished, highly accurate sequence of the mouse genome.
In addition to the University's Genome Sequencing Center, other sequencing centers involved are the Whitehead Institute for Biomedical Research in Cambridge, Mass., and the Sanger Centre in the United Kingdom.
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