Help Decode Genome
Associated Press Writer
12:02 PM EDT; July 16, 2000; Nairobi, KENYA (AP) -- Nibbling away in boxes filled with wood chips in a building overlooking the Ngong Hills, thousands of Kenyan mice are ready for the most important job of their lives. Now that scientists and researchers have mapped about 97 percent of the human genome, they will need a guide to help them navigate the secrets of the genes. The Nairobi rodents, they hope, will be their Virgils.
The genomes of mice and humans are 80 percent identical [homologous]; they have virtually identical sets of genes, but the sequences differ slightly. A comparative study of mouse genes will help explain the significance of the string of 3 billion genetic letters uncovered in the milestone sequencing of human DNA announced in June in Washington. "The human genome sequence stops here. To find the function of the (human) genes, here actually comes the mouse," said Fuad Iraqi, molecular geneticist and gene mapper extraordinaire. In order to determine the function of human genes researchers can remove parallel genes from so-called "knock-out mice," that often reveal by their subsequent defects the natural functions of the genes they lack.
Iraqi, a 39-year-old Arab-Israeli, runs the mouse project at the International Livestock Research Institute (ILRI) on the outskirts of the Kenyan capital. He is one of group of [400 - 500] mouse specialists around the world who meet every so often to compare notes. This year at their meeting in Philadelphia the project to map the mouse genome was officially launched. With about 97 percent of the human genome sequenced, the equipment and resources involved in that endeavor are now being dedicated to the mouse, only the fourth living organism to be genetically mapped. The other two are the roundworm [ C. Elegans] and the fruit fly [ Drosophila melanogaster].
The mouse community will meet again in November in Narita, Japan, to assess progress. Scientists have been using mice in research since 1664 when English physicist Robert Hooke first observed the reaction of the rodents in his experiments on the properties of air. In its April 14 issue, Science magazine devoted 10 pages to what it called "biomedicine's model mammal," detailing the rise of the international mouse trade and citing forecasters who say mouse use could grow by [10 - 20] percent annually over the next decade. What makes the ILRI mice so interesting to researchers is that they represent 13 generations of crossbred strains that can be used for studying genes underlying traits like lung cancer, malaria, and obesity -- all of interest to human beings and pharmaceutical companies.
The average research mouse population is inbred and does not offer such a broad genetic spectrum to choose from. "This is the only mouse population that exists today to find genes in the mouse related to human genes," Iraqi said, holding a wriggling brown mouse by its tail. Prof. Stephen Kemp, Professor of Molecular Genetics at the University of Liverpool in England, said the crosses of the ILRI mice were originally established using lines which differed in their resistance to sleeping sickness, "and they have already provided very fine localization of the genes involved in this important disease."
Because the same lines of mice differ in other ways and have different susceptibilities to many diseases and parasites as well as some important behavioral differences (including a predilection for alcohol), Kemp said the ILRI advanced lines "represent an important resource for scientists wishing to isolate the genes involved in all of these traits."
ILRI's original interest in mice arose from its mission to use biotechnology to improve livestock productivity in developing countries, particularly within the small-holder sector. A part of an international consortium of agriculture and livestock research institutes in developing countries, ILRI is funded through the Consultative Group on International Agricultural Research. Iraqi and Tanzanian colleague Onesmo ole-MoiYoi, a molecular biologist, have both used the mice in their research to map and clone mouse genes associated with parasitic diseases that affect cattle in Africa.
Iraqi's department is currently conducting mouse-based gene research for several U.S. institutions on lung cancer, obesity, and the genetic origins of certain human behavioral traits. He said scientists had been aware of the value of the mouse in genetic research since the early 1980s, but they lacked the tools and resources to exploit them.
Since 1995, the introduction of automated gene-sequencing machines (ILRI has four) [Celera Genomics Group, the private firm involved in the mapping of the human and the mouse genomes, has 300] as well as the creation of the specialized mouse population at ILRI have sped up the process and changed everything. Most of the basic mouse research at ILRI is carried out by a laboratory staff of several hundred Kenyans, something that pleases Iraqi enormously. "When I travel and tell people I work in Kenya, they think we're doing science in the bush. They can't imagine that we have highly trained staff and state-of-the-art laboratories. It doesn't fit in with their Discovery Channel vision of Africa," he said. "Actually, with these mice and these people, the South is showing that it has the potential to assist the North."