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
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
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
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
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
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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