Alberta mad cow case not the result of a genetic mutation

Toronto, ON November 28, 2003 Genetic analysis of Canada’s "mad cow" case indicates that the illness probably did not occur spontaneously, leaving feed containing the infectious agent as the leading theory on the cause of the disease.

A new study, carried out jointly by Health Canada and the Canadian Food Inspection Agency (CFIA) and published in the journal Genome, presents evidence to exclude spontaneous mutation from the list of possible causes of the disease found last May in an Alberta cow. Bovine spongiform encephalopathy (BSE), often referred to as “mad cow disease”, is caused by an abnormal host protein, called a prion, that results in fatal neurological damage.

"All of the actual empirical evidence in past cases has been in favour of an infectious origin such as through exposure to feed containing the infectious protein," says lead author Michael Coulthart, of Health Canada.

But because of the current isolated nature of the case, "there was a second school of thoughtthat it was more likely to be spontaneous in some form," such as an isolated new genetic mutation. New mutations sometimes cause CreutzfeldtJakob disease (CJD), a human disease similar to BSE, in people not previously exposed to the infection.

"Discussions were becoming somewhat polarized on the issue, and we needed a factual basis from which to move forward," Coulthart stresses. To settle the debate, his group collected and analyzed genetic evidence from the Canadian cow.

The researchers determined the sequence of the genetic building blocks that make up the prion gene in the Canadian cow. They then looked for disease-causing mutations in this sequence by comparing it with existing sequences for the same gene from healthy cows and humans affected by genetic CJD.

"We got a very clear negative result," says Coulthart. "We found no mutations."

The study’s results leave the most likely source of infection as exposure to tainted feed, which supports the conclusions reached through the CFIA’s comprehensive BSE investigation and policy implementation. These results will help strengthen the CFIA’s already well-supported efforts in providing science-based, defensible conclusions to the satisfaction of the international scientific and regulatory community.

While not addressed in this study, the question of whether some animals might be genetically predisposed to BSE infection will be the focus of future work. Difficult to test, such susceptibility is known to occur in human CJD and in scrapie, an analogous disease in sheep. Nothing is yet known about this possibility in cattle, but "in terms of ongoing studies, that’s one of the most important things that needs to be done," said Coulthart.

The authors of the paper were Michael B. Coulthart, Rhonda Mogk, Jason M. Rancourt, and Deborah L. Godal, from Health Canada; and Stefanie Czub, from the Canadian Food Inspection Agency.

The full article can be accessed online at: http://pubs.nrc.gc.ca/cgi-bin/rp/rp2_tocs_e?gen_gen6-03_46