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MICROSCOPIC MAP-MAKING A MAJOR PART OF ORNL'S GENOME PROGRAM

 OAK RIDGE, Tenn., Feb. 11 /PRNewswire/ -- Lisa Stubbs is not your average cartographer. Her map-making expertise has nothing to do with ranges, rivers, grids or boundaries, though she is helping construct perhaps the most intricate and comprehensive map ever attempted -- a map of all the genes contained in human DNA.
 DNA (deoxyribonucleic acid) is in the nucleus of most of the 10 trillion cells in a human body. It contains all of an organism's genetic instructions, providing the complete blueprint for physical development. Will a person be tall or short, fat or thin, have blue eyes or brown? More significantly is he a candidate for one of the many inherited diseases, such as cystic fibrosis, muscular dystrophy or some type of cancer?
 The answers to these questions and others related to heredity are strongly influenced by genes, which lie along strands of DNA. It is the work of Stubbs and her research group to plot their positions.
 "The real purpose of all our work, ultimately, is biomedical research," Stubbs, a group leader in the Biology Division at the Department of Energy's (DOE) Oak Ridge National Laboratory (ORNL), said. "If we can find the genes, we'll go far beyond just knowing disease symptoms; we'll actually know what's wrong," she stressed. "Then we'll be able to treat the disease in a very specific way, working on a particular gene or its protein product."
 Charting gene intervals in a map form and discovering more efficient methods for doing so are primary goals of an international effort called the Human Genome Project. The maps will be a guide to a more thorough understanding of the 5,000-plus known inherited diseases and "will provide a key to their diagnosis and treatment from the earliest stages of fetal development," Stubbs said. "And there are many problems in humans that aren't yet recognized as being strictly genetic or as having genetic components," she added.
 The word "map" may evoke the representation of a landscape hundreds or even thousand of miles wide. But a physical genome map is derived from the microscope world of a chromosome, which is actually a very long, tightly-packed strand of DNA.
 If a set of chromosomes could be stretched end-to-end across a table, it would be about six feet long. In reality, chromosomes are so compact that 46 (23 each from the mother and father) fit in a cell's nucleus just one micron in diameter. That's about 50 times smaller than the diameter of a human hair.
 In order to construct their map, Stubbs and her assistants cut the chromosomes into even smaller pieces of DNA.
 They use enzymes to slash a chromosome into tiny fragments so that the order of its fundamental building blocks, called bases, can be closely examined in chunks of about a million. The sequence of the bases determines the synthesis of life's essential proteins. Specific sequences of many bases -- generally thousands -- make up genes. The chromosome fragments are subsequently pieced back together and an intact map is created.
 Just as a map of an interstate highway might show the location of cities and their relative proximity to one another, a physical map of a chromosome shows where genes lie along the molecule's length and indicates the distance between them. "We want to find out exactly where those points are, and the distance from one to the next," Stubbs said. That's crucial knowledge, because the closer genes lie to one another the more likely they will be inherited together, along with their associated traits.
 Stubbs is working to pinpoint trait-encoding genes in humans by studying DNA in mice chromosomes. "Very often, relatives of genes that have a specific role in humans do the same thing in mice," she said. For instance, mouse chromosome number 7, the focus of Stubbs' work, has similarities to human chromosomes 19, 11, and 15.
 Through selective breeding strategies during the past four decades, ORNL's Biology Division has engineered groups of genetically identical mice, as well as lines of mice that have small, consistent and known genetic differences. Using genetically identical mice, researchers can take duplicate pieces of DNA from different mice, treat them in slightly different ways, and observe the outcome. The slightest mutations can impart a wealth of knowledge about the development of different body functions and diseases that may affect them.
 When this knowledge is transferred to treating humans, much suffering caused by now mysterious diseases may be avoided.
 To date, the approximate positions of about 2,300 human genes have been charted by scientists around the world. The human genome is estimated to comprise at least 100,000 genes. "The sheer numbers create the complexity of the project," Stubbs said. "It's an enormous undertaking."
 It is an undertaking that may, in fact, involve 20 more years of dedicated research, Stubbs said. But it is one that will forever enrich the human condition as the map she and her colleagues are now creating unfolds to reveal the passage to an abundance of biomedical advances.
 This research effort is supported by the DOE's Office of Health and Environmental Research.
 ORNL is one of five energy-related facilities managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy.
 -0- 2/11/93
 /EDITOR'S NOTE: If you are interested in a photograph relating to this release please contact the ORNL Public Affairs Office at 615-574-4160/
 /CONTACT: L. Darryl Armstrong, Public Affairs Department, Oak Ridge National Laboratory, 615-574-4160/


CO: Department of Energy's Oak Ridge National Laboratory ST: Tennessee IN: MTC SU:

MM-SB -- CHFNS1 -- 5484 02/11/93 07:35 EST
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