Pinpointing the gene

Pinpointing the gene

Montreal researchers have identified the genes responsible for four rare and sometimes fatal diseases
October 1, 2003

In the Saguenay-Lac St-Jean region of Quebec, one in every 23 residents carries a defective gene that is a potential killer.

And if two people carrying a defective gene have a child, that child develops Leigh Syndrome, French Canadian Type — a deadly disease that generally leads to death before the child is six years old.

The disease is common in the region, affecting one out of every 2,000 live births. Until this year, parents had no way of knowing if they were carriers, or if their children would suffer from Leigh Syndrome. All that has changed. In January 2003, researchers at the McGill University and Genome Quebec Innovation Centre (formerly called the Montreal Genome Centre) announced they had helped to identify the gene associated with the disease. And just as importantly, they had developed a genetic test to identify potential carriers.

"This test is already available to high-risk families — brothers, sisters, aunts, uncles of people with the disease," says Dr. Thomas Hudson, Director of the McGill University and Genome Quebec Innovation Centre. Hudson was particularly pleased that his laboratory played an essential role in identifying the gene (known as LRPPRC) responsible for Leigh Syndrome. The reason? He's from the Saguenay-Lac St-Jean region himself.

"A diagnostic test that can detect carriers and provide improved prenatal diagnostic options will be a boon to the members of our community," Pierre Lavoie said when the gene for Leigh Syndrome was discovered. Lavoie is the president of an association for parents of children who have died of the disease. "Without such a test, parents didn't know if they carried the defective gene until it was too late."

Hudson is proud of other discoveries that researchers at the Centre have made this year alone — including the identification of key genes involved with three other rare diseases. In February 2003, an international research team led by colleague Erwin Schurr and his student Marcello Mira, from the McGill University Health Centre, identified the location of a gene on human chromosome 6 that makes people susceptible to leprosy. Mira is one of four visiting students who joined the Centre in 2002 to access the genome core facility teams in sequencing and genotyping. The other students — from Ste-Justine Hospital, McGill University, and Calgary—were also remarkably successful in their projects. The work eventually led to major scientific publications announcing the discovery of a gene that causes childhood cirrhosis, as well as two different defects in vitamin B12 metabolism that can lead to mental retardation.

At the new $31-million research facility that houses the Centre, which officially opened in September 2003, the team of about 125 researchers is also searching for the genes involved in ovarian cancer, breast cancer, Type II diabetes, heart disease, and schizophrenia. Hudson, a world-renowned leader in the field, is concentrating on the genes involved in asthma. By comparing the DNA of children with asthma with the DNA of kids who don't have the disease, Hudson and his team are hoping to spot mutations at the DNA level. They hope their investigation will lead to new therapies and fewer side effects in drugs used to treat asthma.


Identifying the genes that cause particular diseases, or which contribute to disease development, is the crucial first step in a worldwide scientific quest.

At the McGill University and Genome Quebec Innovation Centre, researchers have had major success in locating the genes associated with several diseases. The next step is coming up with new drugs or other effective therapies to combat the diseases. That's something researchers are struggling with all over the world, says Thomas Hudson, Director of the Centre. "The major reason we find these genes is to try to understand the biology and come up with a treatment for the people who are affected by the disease. These are big projects, but we have basically opened the door to new research avenues and possible treatment strategies," he says.

Hudson's particular field of interest involves asthma, which is the largest cause of emergency room visits in Canada. In the last 20 years, the percentage of children with asthma in North America has doubled—from 5 percent to 10 percent. Hudson believes his research will eventually lead to the identification of different kinds of asthma, some with a genetic and some with an environmental component, which will lead to more effective drug regimens and fewer side effects for patients.


The McGill University and Genome Quebec Innovation Centre is a multi-university centre in Montreal that was built with funds from the Canada Foundation for Innovation, McGill University, Genome Québec, Genome Canada, the Ministère de la technologies, de la science et de la recherche du Quebec, the Donner Canadian Foundation, Mrs. Pierrette Wong, Valorisation-Recherche Quebec, and the McGill University Health Centre.

The Centre works with hundreds of collaborating labs across Canada and around the world to perform high throughput genetic sequencing and genetic analysis. The goal is to identify the genes involved in various diseases and to develop new research avenues for treatment strategies. The Centre is becoming a magnet for the best minds in genomics, incorporating a multi-disciplinary collaboration among mathematicians, engineers, chemists, medical doctors, biologists, and bioinformaticians. It has already generated economic spin-offs of over $4 million. "We're especially happy with the results to date," said Paul L'Archevêque, CEO of Genome Quebec. "The group of science and technology platforms provided by the Centre has so far helped support 120 large-scale genomics and proteomics research projects across Canada, as well as in the U.S. and many other countries."

One of the Centre's frequent partners is the Whitehead/MIT Center for Genome Research in Cambridge, Massachusetts, where Hudson was working before coming to McGill. The Whitehead group was a member of the team that identified the gene causing Leigh Syndrome. "Genomic information is changing the way we tackle disease," says Eric Lander, Director of the Whitehead/MIT Center for Genome Research. "Over the next decade, scientists will increasingly be able to use powerful global tools and integrative strategies to accelerate disease-gene discovery, even for complex, common diseases like diabetes and heart disease."