Chromosome Probes

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.

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