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          ARRoGANT                CoURiERS      WiTH     ESSaYS

Grade Level:       Type of Work           Subject/Topic is on:
 [ ]6-8                 [ ]Class Notes    [General Information     ]
 [ ]9-10                [ ]Cliff Notes    [About Chromosone Probes ]
 [ ]11-12               [ ]Essay/Report   [                        ]
 [x]College             [x]Misc           [                        ]

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Chromosome Probes at the University of Toronto   
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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.
