Powerful Population

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BY AMBER LEPAGE-MONETTE

Walking down the street on any given day, most of us meet or walk past dozens of nameless faces — strangers, who seem as unconnected to us as possible. But what if every third person you passed was really a distant relative, someone who shared part of your genetic makeup? It may seem hard to believe, but chances are, some people out there have a much bigger family than they ever imagined. Such close-knit genetic pools not only exist, but are providing scientists with vaults of much-needed information that may hold the keys to discovering the origins of disease.

This is where the work of Galileo Genomics Inc. (St-Laurent, QC) and vice-president and CSO Majid Belouchi, PhD starts. Combing through the DNA of a genetically homogenic population, Belouchi hopes to discover what causes our ills.

Pop Goes Quebec

To understand Belouchi’s and Galileo Genomics’ work, one must first look at the origins of part of Quebec’s population.

Founder populations — communities of people with common ancestors, descended from an originally limited group — can be found throughout the world. These groups tend to remain genetically tight-knit, not experiencing high intermarriage with outsiders, usually due to various factors such as religion, culture, language or geography. Because of the small number of originators, and the low level of intermarriage with other genetic groups, founder populations contain individuals who share many common genetic traits. Consequently, such populations experience high levels of genetic homogeneity.

Founder populations are seen in communities in Costa Rica, Finland and Newfoundland, among others. One group, the Ashkenazi Jews, shows higher prevalence for several genetic diseases, including Tay-Sachs disease and certain forms of breast cancer. Toronto, Ont.’s Mount Sinai Hospital reports that while mutations in the brca1 and brca2 breast cancer genes occur in 0.1 per cent of the general population, the rate is greater than two per cent in Ashkenazi Jews.

But lucky for Belouchi, one of the world’s most valuable founder populations is right in his own backyard. Of all the founder populations, the Quebec founder population is considered one of the best for genetic mapping, Belouchi explains, because current members are now within 12 to 16 generations of the founders, who were few in number. Though tens of thousands of people emigrated from France to Canada between the early 1600s and the mid-1700s, many returned to France, died or moved to other parts of Canada, leaving the founder population of approximately 2,600. Currently, there are about six million people in Quebec with ancestry that traces back to that original 2,600.

A common misconception people have about the Quebec founder population upon learning about Galileo Genomics’ work with genetic mapping, is that this group has a higher incidence of disease.

“Every time I do presentations to French Canadians, they panic,” Belouchi says. “They think that they have more diseases than others. This is not true . . . It’s just the history of the population that makes it very homogenic and very practical for pinpointing genes in common disease.”

With the assistance of approximately 600 physician and nurse recruiters, and 200 nurses across Quebec who help with taking samples, Galileo Genomics recruits trios — one patient and their two parents. The patients are phenotyped, which is made easier by genotyping the parents. This information is then sorted and searched using linkage disequilibrium (LD) mapping.

LD mapping, or population-based mapping, works by tracking regions found near disease genes that, along with disease genes, are passed on from one generation to the next. These regions contain specific patterns of marker alleles, or haplotypes, which make them easily identifiable, and disease genes are found by detecting the haplotypes. LD mapping is considered statistically more powerful than family linkage mapping, and allows researchers to more easily identify regions that contain one or multiple disease genes.

Galileo Genomics is currently working to target genes implicated in 21 common diseases, including asthma and cardiovascular, psychiatric and bone diseases.

From the Beginning

So how does one start working with a genetically homogenous population, searching through hundreds of thousands of genes in order to find the genes of disease?

After completing his master’s degree and PhD at Notre-Dame Hospital’s Cancer Institute of Montreal — affiliated with the University of Montreal (Montreal, QC) — Belouchi conducted his post-doctoral work at McGill University’s (Montreal, QC) department of Biochemistry, working for three years on drug resistance to pain and the genomics of infectious disease.

Belouchi was then recruited by Algene Biotechnologies Corp. — which eventually became Signalgene Inc. (Montreal, QC), and recently signed a subscription agreement with Network Capital Inc. (Calgary, AB) — to set up a molecular biology lab.

It was at Algene Biotechnologies that Belouchi and his team started working with LD mapping and the Quebec founder population, thanks to Algene Biotechnologies’ founder and former president, Denis Gauvreau, PhD.

“This was his baby,” Belouchi says. “He was ahead of his time. He was trying to use the linkage disequilibrium on the founder population and we were at that time working on Alzheimer’s disease.”

Gauvreau’s Alzheimer’s project was quite extensive, Belouchi explains. “It was like a 17-year project. He assembled a collection of about 700 Alzheimer’s brains — it’s really something impressive.”

But the work at Algene Biotechnologies hit several snags, Belouchi says. At the time, he explains, there wasn’t enough knowledge of the human genome sequence, there weren’t enough genetic markers identified and existing technologies could not perform the required mapping cost-effectively. Algene Biotechnologies researchers worked to discover the regions of two disease genes, schizophrenia and Alzheimer’s. Due to financial and technological constraints, the work on both regions was ended, and the schizophrenia gene work was sold to Janssen Pharmaceutica N.V. (Berchem, Belgium), which eventually identified the gene.

After working at Algene Biotechnologies for three or four years, and having been promoted to the position of the company’s scientific director, Belouchi, along with several other Algene Biotechnologies researchers, left the company over administrative problems.

“I felt very frustrated by the people when I was trying to tell them that we can be successful at Algene,” Belouchi says. “I spoke to tons of politicians there, including the Board of Directors, scientists, former ministers that were on the Board, etc. . . . to tell them that we have really a gold mine in Quebec.”

Despite his best efforts, Belouchi says people at Algene Biotechnologies could not be convinced of the work’s potential. He says he felt that some of his colleagues did not trust him when he asserted what he felt would be the company’s certain success with LD mapping. Galileo Genomics was founded, in part, Belouchi says, to show those doubters that the work would be successful and that his convictions had been right — something he says he is still working to prove.

Galileo Genomics got its true start when it signed its first contract with Myriad Genetics Inc. (Salt Lake City, UT) in September 1999, conducting genetic analysis and assisting with recruitment for Myriad Genetics, which works with the Mormon founder population in Utah. Belouchi and his colleagues had worked with Myriad Genetics while they were with Algene Biotechnologies, and when Algene Biotechnologies publicly announced it would not be pursuing business with Myriad Genetics, Belouchi says he got the go-ahead from lawyers to contact Myriad Genetics. A $2.2-million contract with Myriad Genetics to work on obesity, major depression and coronary heart disease followed.

Once the new company was underway, Belouchi recognized that strong management would be important to Galileo Genomics’ success.

“I learned that 80 per cent of the success of a scientific company is related directly to the management. If you have bad management, you can have the best scientists in the world and it will go nowhere,” he says. “If you have a very good management, your chances of success are very high.”

Though Belouchi founded Galileo Genomics, running the company seems to be something that is far from his mind, and businessman is not a job position in which he readily sees himself.

“Many of my friends are businessmen, my father was a businessman. So I understand very, very much the business,” Belouchi says. “But I hate money. I hate speaking to business people. I understand all the aspects of business, but at the same time, I hate it. This is why I was not the president of this company.”

Renaissance Man

Though he doesn’t see himself as a businessman, Belouchi also seems reluctant to categorize himself as a scientist, noting that he is equally an artist, practising woodworking, painting and architectural maquettes, which a friend in Morocco uses to build houses, he says.

Belouchi was also, years ago, a semi-professional soccer player. “In Montreal they called me The Hammer because I was a striker. I scored two, three goals every game,” he says. Playing for several teams in his early twenties, Belouchi says his soccer-playing days are still something to be remembered. “There are places where people tell me that there is still my photograph there (in the Portuguese neighbourhood),” he says. “This is like 15 years ago. I was like, (a) superstar.”

Despite his varied interests, science is obviously very much part of his life, and Belouchi feels it’s his scientific goals that set him apart. “I am very specialized, very different from people . . . I have a very strong vision, very real,” he says.

“I am very strong in development. For example, I can see any technology or any problem in science and I have more than, like, 85 per cent chance to develop something better,” Belouchi explains.

The View Ahead

With all this vision and determination, Belouchi seems quite certain where Galileo Genomics will find itself down the road.

Not only does Belouchi see the company going far in its scientific endeavours regarding LD mapping, but he personally sees this success translated into the company’s inevitable end.

“I think that . . . we are going to be eaten by a big pharma, because our discoveries are going to be in the first, or short-term, used to develop diagnostics, which is the obvious thing to, and easy thing to do,” Belouchi says. “The medium long-term, is to take this information about the gene to develop drugs.”

His confidence lies in his long-standing belief in his work and in the hidden gem he feels he has found in the Quebec founder population. All that needs to be done now is to follow through on what he knows can be done.

“If we find one gene, people will say it is chance. If we find two genes, we are very lucky,” Belouchi says. “If we find three or four genes, then it’s not luck, it’s the method.”