LOS ANGELES (Nov. 29, 1999) ‘V Imagine a drab satellite photo of the United States, clipped into tiny pieces and strewn across a tabletop. If someone handed you one scrap and asked you to guess the location, where would you begin?
The dilemma is not unlike the one that has been faced by scientists trying to elicit practical information from our evolving knowledge of the human genome.
Using rough guides, guesswork, and months of arduous trial and error, they have struggled to identify certain breaks on chromosomes that indicate an aggressive form of cancer, or clues to a sick child's genetic diagnosis. But the landmarks are few and the necessary information elusive, hidden among millions of basepairs on each chromosome.
Dr. Julie R. Korenberg, who holds the Geri and Richard Brawerman Chair in Molecular Genetics at Cedars-Sinai Medical Center, has now devised the first comprehensive color-coded guide to the human genome. The culmination of eight years of work by her research team at Cedars-Sinai and associates at the Massachusetts Institute of Technology, her study appeared in the October issue of the scientific journal, Genome Research.
The effort integrates three ways of looking at the human genome by marking critical points with lantern-like signposts that can be seen under a fluorescent light. Therefore, if a scientist wants directions to a site known (or suspected) to exist on a genetic, physical, or transcript outline of the genome, he or she needs only follow the illuminated colors to its neighborhood.
On the proverbial satellite photo described above, Korenberg's map would point you to the correct zip code, if not the precise street address. ‘§This has tremendous practical application," said Dr. Korenberg. "It makes the invisible visible by providing a means of translating clinical problems rapidly into the genome." For example, an oncologist could examine a patient's DNA to see whether she had an aggressive or slow-growing form of a particular cancer and use the information to design an appropriate chemotherapy schedule.
A pediatric specialist could quickly diagnose a newborn's precise genetic disorder by zeroing in on suspect regions of the baby's DNA. "Instead of this taking months and months, it could be done in a single experiment," said Dr. Korenberg. The map can be used as well to help unravel genetic and evolutionary mysteries, she explained. Unlike some proprietary guides to the genome, Dr. Korenberg's complete map is available to anyone doing genetic research or using DNA to solve practical medical problems.
Relevant sites on the genome are marked by signposts called bacterial artificial chromosomes (BAC) These are bacteria stripped of their essence and used as containers for actual stretches of human DNA that are illuminated and can be seen through a microscope. The BACs on Dr. Korenberg's map are linked to existing genetic and physical maps of genome sections tagged with polymerase chain reaction-based sequence tagged sites (STS). For example 1,021 links were made between STS and BAC-identified points on the genome. Previously mapped genes are clearly identified as well. To devise the map, the double helix of DNA was separated. Each sequence was broken into tiny pieces and tagged with a BAC-illuminated with fluorescent material. When a marked chromosome found its ‘§mate‘¨ on the other side of the double helix, its proper location in the sequence could be discerned. The information unveiled during the process not only fills in the blanks on innumerable sites within the genome, but provides the best bridge yet between basic bench science and applicable clinical needs. Dr. Korenberg's study is entitled, ‘§Human Genome Anatomy „o BACs (Bacterial Artificial Chromosomes) Integrating the Genetic and Cytogenetic Maps for Bridging Genome and Biomedicine.‘¨
Co-authors included Xiao-Ning Chen, a member of Dr. Korenberg's research team in the Medical Genetics Birth Defects Center at Cedars-Sinai; Jean S. Weissenbach of Genoscope, Evry Cedex, France; Melvin I. Simon of the California Institute of Technology; Bruce Birren and Thomas J. Hudson of the Massachusetts Institute of Technology and Montreal General Hospital Research Institute at McGill University.
Significant funding for the study was provided by the U.S. Department of Energy and the National Institutes of Health.
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The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.
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