Essay, Research Paper: Chromo(A)

Chromosome Probes at the University of Toronto Sensitive chromosome probes recently discovered by aUniversity of Toronto geneticist will make it easierto detect certain types of genetic and prenataldiseases, as well as being used to determine paternityand provide forensic evidence in criminal cases. Probes are short pieces of DNA which bind to, andactually pinpoint, particular sites on a chromosome. Because these new probes are actually repeated hundredsor thousands of time at a particular site, they aremuch more sensitive than previously available ones. Of the 23 pairs of human chromosomes, Dr. F.H. Willardhas discovered repeated probes or markers for six plusthe gender determining X and Y chromosomes. "Whatwe're trying to decide now is whether to isolate probesfor the other chromosomes, or whether we shouldutilize the eight we have," he says. Dr. Willard is currently negotiating with an Americancompany to develop prenatal diagnostic tests, which,because the current tests are time consuming andtechnically difficult to do, are restricted to womenover 35 and those who have a family history ofchromosomal abnormalities. Prenatal tests usingWillard's probes would be much simpler and faster toperform and could be available to all pregnant womenwho wish to take advantage of the technology. Current prenatal testing involves growing fetal cellsin vitro and examining them, over one or two months, tosee if there are two copies of a particular chromosome,which is normal, or one or three, which is abnormal. Atest using Willard's probes would require only a fewcells and a few days to detect abnormalities. "I don'tthink it's beyond the realm of possibility that thesekinds of tests could eventually be done by anobstetrician in the office during the early stages ofpregnancy," he adds. The determination of gender is another possible use forthe probes. Many diseases, such as Duschene's musculardystrophy, show up on the X chromosome, manifestingonly in boys. Willard thinks it is possible to developa 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 genitaliais another medical reason for using the test. A quickexamination of the X and Y chromosomes of the childwould indicate whether genetically the child is male orfemale. As yet, Willard has been unable to develop a probe forchromosome 21. Down's Syndrome results from threecopies of chromosome 21 (trisomy 21). "I think we'llknow within a year whether a test to detect trisomy 21is feasible, " he says hopefully. The other six chromosome probes which Willard hasdeveloped do not immediately lend themselves todiagnostic tests, except for certain cancers, he says. "We have a probe for chromosome 7 and we know thattrisomy 7 is a signal for certain types of cancer. Chromosome abnormalities of all kinds are a signpostof tumors." Theoretically, an oncologist could use a chromosome probe test to examine tissue and obtain areading for a specific cancer. " It wouldn't suggest amode of therapy," he points out, "but would be a speedytest and would have prognostic implications for thekind of tumor discovered."As a basic research tool, Willard's probes could be usedto develop a genetic linkage map for humanchromosomes. "It's important to know the location ofgenes in the human genome, particularly disease genes. The leading approach to try to sort out disease genes isto use genetic linkage. Because our sequences are at thecentromere it would allow us to develop a map."The third application for the probes is in forensicbiology. Willard believes his markers are as unique toeach each individual as are fingerprints. According tothe geneticist, it will be possible to make a DNA 'fingerprint' from blood or sperm, which could be usedas evidence in rape or murder cases. "We haven't yetdone the analysis which confirms that our probes areDNA fingerprints, but once we do, we will make themavailable for development into tests."As research progresses in all these areas, Willardhopes to collaborate with other departments at the U ofT to conduct clinical trials. His work is funded by theMarch of Dimes, the Hospital for Sick ChildrenFoundation and the Medical Research Council.