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ФФФФФФФФФ>ФФФФФФФФФ>ФФФФФФФФФ>Chop Here>ФФФФФФФФФ>ФФФФФФФФФ>ФФФФФФФФФ>ФФФФФФФФФ ======================================================= Chromosome Probes at the University of Toronto ------------------------------------------------------- Uploaded: November 29, 1986. Sensitive chromosome probes recently discovered by a University of Toronto geneticist will make it easier to detect certain types of genetic and prenatal diseases, as well as being used to determine paternity and provide forensic evidence in criminal cases. Probes are short pieces of DNA which bind to, and actually pinpoint, particular sites on a chromosome. Because these new probes are actually repeated hundreds or thousands of time at a particular site, they are much more sensitive than previously available ones. Of the 23 pairs of human chromosomes, Dr. F.H. Willard has discovered repeated probes or markers for six plus the gender determining X and Y chromosomes. "What we're trying to decide now is whether to isolate probes for the other chromosomes, or whether we should utilize the eight we have," he says. Dr. Willard is currently negotiating with an American company to develop prenatal diagnostic tests, which, because the current tests are time consuming and technically difficult to do, are restricted to women over 35 and those who have a family history of chromosomal abnormalities. Prenatal tests using Willard's probes would be much simpler and faster to perform and could be available to all pregnant women who wish to take advantage of the technology. Current prenatal testing involves growing fetal cells in vitro and examining them, over one or two months, to see if there are two copies of a particular chromosome, which is normal, or one or three, which is abnormal. A test using Willard's probes would require only a few cells and a few days to detect abnormalities. "I don't think it's beyond the realm of possibility that these kinds of tests could eventually be done by an obstetrician in the office during the early stages of pregnancy," he adds. The determination of gender is another possible use for the probes. Many diseases, such as Duschene's muscular dystrophy, show up on the X chromosome, manifesting only in boys. Willard thinks it is possible to develop a test which would quickly indicate the fetus' sex. This would benefit parents whose only option is to have no children or to have only girls. Confirming gender in children with ambiguous genitalia is another medical reason for using the test. A quick examination of the X and Y chromosomes of the child would indicate whether genetically the child is male or female. As yet, Willard has been unable to develop a probe for chromosome 21. Down's Syndrome results from three copies of chromosome 21 (trisomy 21). "I think we'll know within a year whether a test to detect trisomy 21 is feasible, " he says hopefully. The other six chromosome probes which Willard has developed do not immediately lend themselves to diagnostic tests, except for certain cancers, he says. "We have a probe for chromosome 7 and we know that trisomy 7 is a signal for certain types of cancer. Chromosome abnormalities of all kinds are a signpost of tumors." Theoretically, an oncologist could use a chromosome probe test to examine tissue and obtain a reading for a specific cancer. " It wouldn't suggest a mode of therapy," he points out, "but would be a speedy test and would have prognostic implications for the kind of tumor discovered." As a basic research tool, Willard's probes could be used to develop a genetic linkage map for human chromosomes. "It's important to know the location of genes in the human genome, particularly disease genes. The leading approach to try to sort out disease genes is to use genetic linkage. Because our sequences are at the centromere it would allow us to develop a map." The third application for the probes is in forensic biology. Willard believes his markers are as unique to each each individual as are fingerprints. According to the geneticist, it will be possible to make a DNA 'fingerprint' from blood or sperm, which could be used as evidence in rape or murder cases. "We haven't yet done the analysis which confirms that our probes are DNA fingerprints, but once we do, we will make them available for development into tests." As research progresses in all these areas, Willard hopes to collaborate with other departments at the U of T to conduct clinical trials. His work is funded by the March of Dimes, the Hospital for Sick Children Foundation and the Medical Research Council.