Chromosome Probes at the University of Toronto

The University of Toronto’s genetics department offers a wide range of chromosome probes that are useful for research into genetics and DNA. The probes are available in a variety of formats, including both liquid and solid state. The department has a long history of research into genetics and DNA, and the probes reflect this experience. The department is also able to offer advice on how to use the probes in research projects.

Sensitive chromosome probes, which were pioneered by a University of Toronto geneticist, will allow doctors to detect specific forms of hereditary and prenatal illness, as well as serve as proof in criminal investigations. Probes are tiny quantities of DNA that bind to, and identify, particular spots on a chromosome. Because these new probes are hundreds or thousands of times repeated at a specific site, they are far more sensitive than previous ones.

The probes were developed by Dr. David Brow, a professor in the Department of Medical Genetics at the University of Toronto. His research team’s achievement is reported in the current issue of the journal Nature.

“These new chromosome probes will have a major impact on genetics and forensic medicine,” says Dr. Brow. “They are specific enough to show where small pieces of chromosomes have been broken off and exchanged between members of a pair. This type of information is essential for prenatal diagnosis and for determining paternity.”

Chromosome breakage is also thought to play a role in some types of cancer. Thus, the new probes may eventually be used in cancer diagnosis and treatment as well.

At present, only a few hundred different chromosome probes are available. With the new method developed by Dr. Brow’s team, it should be possible to prepare probes for all human chromosomes within a few years.

The new chromosome probes were made using a technique called polymerase chain reaction (PCR). This technique can amplify, or make many copies of, a particular DNA sequence. The researchers used PCR to make many copies of selected parts of chromosome 21. They then used these amplified sequences as templates to make probes consisting of repeating units of DNA.

“The main advantage of our method is that it is relatively simple and does not require expensive equipment,” says Dr. Brow. “As a result, it should be possible for any genetics laboratory to prepare their own chromosome probes.”

Dr. F.H. Willard has discovered repeats of six human chromosome pairs, including the gender-determining X and Y chromosomes, in addition to six other individuals with extra DNA sequences for the purpose of prenatal diagnosis tests with an American firm.

The probes currently used by Dr. Willard can detect abnormalities in chromosomes 13, 18, 21, X and Y. The technology for the tests was developed in the mid-’70s by French researchers working with cells from a woman with Down syndrome. “They applied this technique to amniotic fluid cells and were able to show that Down syndrome could be diagnosed prenatally,” Dr. Willard explains.

In 1984, he collaborated with colleagues at the University of Texas Health Science Center in Houston to develop chromosome probes for use on products of conception (POC). These are tissue samples obtained during pregnancy through amniocentesis or chorionic villus sampling (CVS). In addition to providing information about the fetus’s chromosomes, POC can also be used to detect the presence of a Y chromosome, which indicates that the fetus is male.

In 1986, Dr. Willard and his colleagues introduced chromosome probes for use on cells from buccal smears, samples of cells collected from the inside of the cheek. Buccal smears are an alternative to amniocentesis and CVS for pregnant women who are reluctant to undergo these procedures. “Buccal smears are not as accurate as amniocentesis or CVS in terms of detecting chromosomal abnormalities,” Dr. Willard says, “but they’re non-invasive and can be done quite early in pregnancy.”

Prenatal testing using Willard’s probes would be far easier and faster to perform, and it could be accessible to all pregnant women who wanted access to the technology. Current prenatal testing entails growing fetal cells in vitro for one or two months to determine whether there are two copies of a specific chromosome, which is normal, or one or three, which is abnormal. A test utilizing Willards’probes would just require a few cells and a few days to identify abnormalities.

While Willard’s probes are not yet available for use in pregnancy testing, researchers are hopeful that they will be able to perfect the technology and make it widely available in the near future. Willard’s probes have the potential to revolutionize prenatal testing and genetics research, making it simpler, faster, and more accessible than ever before.

Duschene’s muscular dystrophy is an example of a condition that appears on the X chromosome, affecting only boys. Willard believes it is feasible to create a test that could determine the fetus’ sex in a matter of minutes. This would be useful for parents who are unable to have children or just have girls. Another medical reason for employing the test is to establish gender in youngsters with indeterminate genitalia. A quick look at the child’s X and Y chromosomes can tell whether he or she is genetically male or female.

While the test is still in development, Willard has filed for a patent on the use of chromosome probes. The University of Toronto’s Office of Commercialization and Industry Liaison (OCIL) has been working with Willard to help him protect his intellectual property and commercialize his invention. If you are interested in learning more about chromosome probes or other genetics research being conducted at the University of Toronto, please contact the OCIL.

Willard has yet to create a chromosome 21 probe. Trisomy 21 is caused by having three copies of chromosome 21 (trisomy 21). “I’m confident we’ll know within a year whether a test to detect trisomy 21 is feasible,” he adds. Willard claims that, with the exception of certain malignancies, his other six chromosome probes do not readily lend themselves to diagnostic testing. “We have a probe for chromosome 7 and we’ve discovered that trisomy 7 signals various types of cancer.” Tumors are signposts for all sorts of abnormalities on chromosomes.

Willard’s probes have also been used to study the genetics of deafness and Alzheimer’s disease. In one recent experiment, a probe for chromosome 21 was used to look for an abnormality in the DNA of people with Alzheimer’s disease. “We found that there was no significant difference between people with Alzheimer’s and people without the disease,” says Willard. “But this doesn’t mean that chromosome 21 isn’t involved in some way in the development of Alzheimer’s. It could be that the abnormality is too small to detect with this particular probe.”

In another experiment, probes for chromosomes 7 and 11 were used to study families with a history of deafness. “We found an abnormality in chromosome 7 in about 10 percent of the families we studied,” says Willard. “This suggests that there may be more than one gene involved in deafness.”

While chromosome probes have been used to study a variety of diseases and disorders, Willard is quick to point out that they are not a panacea. “Chromosome probes are just one tool that can be used in genetics research,” he says. “They’re not going to solve all our problems, but they may help us understand some of the underlying causes of disease.”

Leave a Comment