The genetic makeup (or genome) of the mouse, one of the most frequently used mammals in medical and behavioral research, will be deciphered in a major new research program launched this month by the National Institutes of Health (NIH).
Ten laboratories, called the Mouse Genome Sequencing Network, collectively will receive $21 million for the first seven months of funding. Mapping, which is determining the physical organization of the mouse's 21 chromosomes, and sequencing or identifying the order of the estimated three billion chemical bases, or letters, of the DNA in the mouse genome, are expected to be completed in working draft form in three years.
"Because mice and humans share many of the same fundamental biological and behavioral processes, this animal is one of the most significant laboratory models for human disease," said NIH Director Dr. Harold Varmus. "Knowing the genetic make-up of the mouse, and being able to compare it to the DNA of humans and other animal species, will greatly expedite many avenues of research including assessing predisposition to disease, predicting responses to environmental agents and drugs, and designing new medicines."
The value of the mouse genome to a wide spectrum of biomedical scientists is illustrated by the funding of the Mouse Genome Sequencing Network by NIH. "Every institute at NIH, with support of the NIH Office of the Director, has made a contribution to the first year of funding for the Mouse Genome Sequencing Network, demonstrating the importance of this work to research progress in virtually every area of biomedical research from hereditary hearing impairments to Alzheimer's," said Dr. James F. Battey, director of the National Institute on Deafness and Other Communication Disorders of NIH and co-chair of the Trans-NIH Mouse Genomics and Genetics Resources Coordinating Group.
Research on the mouse genome will occur in two stages, following the strategy now being used by the international Human Genome Project to sequence the genetic blueprint of the human. Scientists working on the mouse genome first will focus their efforts on completing an intermediate working draft version of the animal's genetic instructions. This first stage will be completed no later than 2003. They then will turn their attention to filling any gaps in the draft and finishing the sequence in high quality, final form by 2005.
"Many scientists have told us that sequence data, even in working draft form, is very useful to their research. For that reason, the Human Genome Project and now the mouse sequencing effort will complete their work in these two stages," said Dr. Francis Collins, director of the National Human Genome Research Institute (NHGRI) of NIH. NHGRI is leading the NIH's participation in the Human Genome Project.
By spring 2000, the Human Genome Project will produce a working draft of the genetic blueprint of the human. By 2003, or possibly sooner, the finished, high quality version of the human genome will be completed.
One quarter of the human genome already has been sequenced by an international consortium of research centers including three laboratories supported by NHGRI. All of the sequence data is made freely available to the public within 24 hours via GenBank (http://www.ncbi.nlm.nih.gov/Genbank/ index.html), the public database operated by NIH. GenBank collaborates with public genome databases in other countries to insure that new data that is deposited into one is included in the other public databases.
"The success of the Human Genome Project, the recent advances in technology, and the broad support from the scientific community have allowed the NIH to take on sequencing the mouse genome," said Dr. Collins. "Prior to last year, this task was not officially one of our goals because several years ago it seemed too daunting to try to sequence both genomes."
This international sequencing effort has already deciphered the genomes of the bacterium E. coli, which has five million base pairs in its genetic blueprint; Baker's yeast, with 12 million base pairs; and the roundworm, C. elegans, with 97 million base pairs. The genome of the fruitfly, with 140 million base pairs, will be completed soon.
"By identifying and studying the genes in progressively more complex organisms, from bacteria and yeast to mouse and human, scientists will have the opportunity for the first time in history to identify and ultimately to understand the genes that are crucial to life," said Dr. Collins.
All applicants for participation in the Mouse Genome Sequencing Network underwent the rigorous evaluation that characterizes the NIH grants awards system. A key consideration in the selection of these grants was the applicant's ability to sequence DNA accurately and efficiently.
"Another important factor in selecting some of the participants is their potential to initiate new sequencing centers," said Dr. Collins. "Increasing the number of labs capable of large scale genomic DNA sequencing will promote the dissemination of genome sequencing technology and related resources at more universities and research institutions in the U.S."
The Mouse Genome Sequencing Network participants are universities and research institutions from across the U.S. "We look forward to future cooperation with other research labs, particularly outside the U.S., who join the mouse genome sequencing effort, just as academic centers in other countries joined the consortium to sequence the human genome," said Dr. Collins.
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