Finding the genes for diseases (and behaviors) in dogs, part 2

PUBLISHED ON April 12, 2018 by jessica hekman

So you’re trying to figure out which genes influence a particular trait, like aggression in dogs. Where do you start? One logical approach is to think about which genes are good candidates, based on what we already know, and investigate those. Studies using this approach to genetics are called “candidate gene studies.”

Do not take his bone by David Shankbone, from Wikimedia

For example, you might read the scientific literature and discover that there’s some evidence that the MAOA gene is associated with aggression in humans. You’d hypothesize that the MAOA gene might affect aggressive tendencies in dogs, as well. You’d collect a bunch of dogs, some aggressive, some not, and sequence their MAOA genes. You’d find all the places in those genes where the sequence varies between dogs – those are called variants. And you’d do some statistics to see if any of the variants are associated with aggression. Then you would sit back and let the fame and fortune roll in.

It’s not a bad approach, but it has some pitfalls. First, how do you know that the variant you found that is associated with aggression is actually affecting the dog’s personality to make him more aggressive? In other words, how do you know if it is what we call the causal variant? It may just be close on the genome to another variant which is the actual causal variant. (And when we say “close” on the genome — well, the genome is a big thing and “close” can mean a lot of different distances.)

Second, if you do your study and you find nothing, you’ve spent a lot of time on collecting data samples – getting dog owners to fill out questionnaires and give you saliva or blood samples, and by the way, thanks to all you guys for doing that for us! You could have used those samples to spread a wider net and tried to find other genes which might affect aggression. The Darwin’s Dogs approach is to spread that wider net, using genome wide approaches. This means that we look at the entire genome for associations instead of guessing at genes that might affect the traits we’re interested in. This approach often returns a region which is associated with the trait of interest – the gene or regulatory region that’s affecting that trait is in the region somewhere, but it will take more work to find exactly where. This approach is a great way to make new discoveries. You might be surprised how often these sorts of approaches find new genes that we’d never have guessed affected a particular trait! There is still so much in the unknown depths of the genome that we don’t understand. It’s the frontier of the 21st century.

Both the candidate gene approach and the genome-wide approach have their place. Candidate gene studies are a great way to follow up on the associations that are found in genome-wide studies, for example. As we explore deeper into this frontier of the genome, it’s a good idea to have as many tools as possible at our disposal, and to know the pros and cons of using each. Behavioral genetics works better with lots of subjects, so if you haven’t enrolled your dog yet, now is the time! And tell your friends!

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