The original settler population expanded rapidly, but, for linguistic and religious reasons, remained isolated. In the 1800s, a million people headed south seeking work in the mills of New England. For those who stayed, "if you married into Protestant community, then you were usually absorbed by it," says Nathalie Laplante, director of ethics and clinical recruitment at Genizon, "but it's much more open today" since the "quiet revolution" of the 1950s. "The Quebec founder population is changing — our society is very open to other cultures. But for purposes of our approach, we insist patients have four French-Canadian grandparents. Studies using this approach would probably be difficult to do in a future generation."

A phenomenon called "demographic genetic drift" means that there is a major over-contribution of some highly prolific families who provided increased genetic homogeneity. There are, for example, an estimated 280,000 living descendants of the union between Pierre and Anne Tremblay in 1657. The couple had 12 children, 10 of whom had children.

The French-Canadian population represents the largest genetically homogeneous localized founder population in the world. That homogeneity is especially intense in some regions. "Fifteen years ago, Canada was a leader in genomics," says Genizon chief scientific officer Majid Belouchi. "They found more than 20 percent of single genetic disease genes in Saguenay-Lac-St-Jean. People are happy to volunteer blood for research."

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