What Kind of Mutant Are You?

We all have gene mutations. Some could be trouble, but many are harmless. How do we know which is which? That's the big riddle.

 |  Transcript [PDF]

Unless you’re into X-Men, a gene mutation is usually seen as something negative, something that causes disease. Even in the X-Men franchise, which popularized the term mutant as someone with odd or amazing abilities, there was controversy over whether mutants are dangerous and should be allowed in society.

But actually, many mutations are completely invisible or silent. In fact, each of us has about 100 mutations or genetic variants and most of them have no visible effect on our lives.

“The real challenge is to figure out which of these mutations don’t matter… and which of them we should worry about,” says Professor Fritz Roth, a molecular biologist at the University of Toronto.

Roth’s team spends their days trying to solve this puzzle and they use several approaches to do it.

The first is statistical: how many people with a certain variant end up with a certain disease? This is the type of information that at-home genetics tests like 23andMe use to provide disease risk – given a certain genetic variant, what are your chances of developing a certain disease? This approach has been successful for diseases like Parkinson’s and late onset Alzheimer’s.

But this approach is also inherently delayed. We need lots of information about many people before we can make conclusions. What Roth is really excited about is an approach that is more predictive. It’s called deep mutational scanning.

“Could we… test all possible mutations in a gene ahead of time?” asks Roth.

This way, even if we have never seen a certain mutation in a human before, we would already know what it did and whether we need to worry about it or not, if it ever appeared in the clinic.

For this approach we need collaboration between molecular biologists like Roth, with geneticists, engineers, and computer scientists. This is the future.

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Frederick (Fritz) Roth trained in physics and biology at UC Berkeley, in biophysics at Harvard, and in industry at Millennium Pharmaceuticals. His research team (ten years at Harvard Medical School and six years at the University of Toronto and Sinai Heath Systems) develops technologies to identify how DNA changes lead to observable effects, and to specifically identify those DNA changes that cause disease. Current interests include improved technologies to map protein-protein interactions under different conditions, and to measure the functional impact of all possible mutations for proteins associated with human disease.