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.