Sunday, September 29, 2013

2013 Canine and Feline Genetics Conference

I was privileged to attend the 7th International Conference on Advances in Canine and Feline Genomics and Inherited Diseases this past week at the Broad Institute in Cambridge, Massachusetts. It wasn’t a large conference: about 150 dog and cat genetics researchers who get together every year and a half or so to catch each other up on what they’ve discovered recently, give each other suggestions about how to proceed or where to get good samples, and give their graduate students a chance to give some talks. I took notes on Twitter (#canfelgen) on my favorite talks (er, those of them that were not too technical; there were quite a few talks that I enjoyed hugely but that did not lend themselves to 140 character summaries). My apologies in advance if I got anything wrong; I was typing with my thumbs as fast as I could and may have made some mistakes.

Robert Wayne, Analysis of recent and ancient canine genomes suggest a new hypothesis for dog origins
Robert Wayne of UCLA talked about ancient canid genomes and “a new hypothesis for dog origins.” We are still not sure which gray wolf population was directly ancestral to modern dogs, and his work has shown that in fact no single population appears to fit the bill. Wayne believes that in addition to all the gene mixing between dog and wolves since domestication (which obviously muddies the picture), there was an ancient population of canids that gave rise to both dogs and wolves which we have not yet found samples from.

Wayne explained that ancient populations of wolves were much more diverse genetically than modern day populations, and we will really need to look to those ancient populations to solve the mystery of dog origins. About 10,000 years ago, populations of both wolves and dogs shrank dramatically in size, which explains why wolf populations are less diverse today than before that bottleneck. This was right around the time that domestication may have been happening, but we don’t know if the events are related.

So, based on this information, Wayne Lab embarked on a study of ancient canid DNA, comparing samples from dogs and wolves both from about 15,000-30,000 years ago. They found that the oldest dog populations were in Europe, not Asia. One interesting finding was in the black coat gene, which was relatively recently introduced from dogs into wolves and has swept through wolves. Apparently, being homozygous for black coat reduces fitness in wolves, but being heterozygous increases fitness. They don’t know why yet.

Wesley Warren, Genetic signatures of selection in the domestic cat lineage
Wesley Warren of the Washington University School of Medicine talked about using cats as models to study domestication. Comparing what we know about the behavior of cats to work in other species (dogs, horses, and chickens), he hypothesizes that cats aren’t actually undergoing significant domestication at all, because they are still very competent at living independently from humans and hunting their own prey. He talked about his work developing a SNP chip for cats, to aid in future genomic research in that species. A SNP chip is basically a library of known polymorphisms in the cat genome — single nucleotides that are known to differ between different individuals. Having all of these SNPs cataloged and available for use on a chip makes looking for correlations between these differences and things like behaviors or diseases much easier. At one point, his chip was used to discover the gene for curly coats in cats.

Warren talked about his recent work comparing the genomes of domesticated cats with their nearest wild relative. He found differences in RALY, a coat color gene. He found that cats have fewer receptors for smell than dogs do, but more for pheromones, and he wants to compare both olfactory and pheromone receptor genes in domesticated cats to big cats. He also talked about the 99Lives project, a project to get more cats sequenced (a theme which was returned to later in the conference).

Anna Kukekova, Simple behavioral pattern: is it simple?
Anna Kukekova of the University of Illinois talked about her work with tame foxes (if you don’t know about the Russian farm fox project, check out the excellent summary at the Thoughtful Animal). Kukekova opened by demonstrating the difference between the lines of foxes selected for tameness and the foxes selected for aggression with video in which a researcher performed a behavioral test on one fox from each line: first standing by a fox’s cage, then opening the door and reaching for the fox, then trying to pet the fox. The videos, shown side by side, were dramatically different: on the left, a clearly wild animal, both cowering from and menacing the human who stood near it. On the right, an animal reacting to human presence just as a dog in a shelter might, almost in a spasm of enthusiasm, wagging its tail, soliciting affection, rolling over to let the human pet its belly. Kukekova talked about analyzing the differences in behavior statistically, and how some of the most important behaviors they found for consistent differentiation between the populations were pricking ears forward, wagging tails, and approaching humans.

Kukekova investigated foxes which were second-generation crosses between tame and aggressive lines. The tame behavior was highly heritable, which was already known. Animals with heritage from both lines usually showed intermediate behavior, on the spectrum between tameness and aggression. What was interesting was that some of the crossed animals showed what she called “switching” behavior: the animals showed tame behavior at some points in the test, and aggressive behavior at others. For example, some of these animals were aggressive to humans who stood at their cage doors, but friendly when the door was opened. Others were friendly when the door was closed, but aggressive once it was opened.

Tara Baxter, Genomic approaches to identify putative canine behavior-associated genes
Tara Baxter of Cornell talked about her method of trying to track down some genes that are associated with different behaviors in dogs. This is a tough problem, as behaviors are usually influenced by multiple genes as well as by the environment, so tracking down a gene that influences aggression (for example) is a lot harder than tracking down a gene that is all by itself responsible for a disease. Baxter reviewed test results from owners who filled out a CBARQ (behavioral survey) about their dogs; she had access to a database of 19,000 surveys, so an impressive sample size. Using these tests, she averaged behaviors for each breed, getting a score of how likely animals of a particular breed were to display a particular behavior (for example, “begging”). Then she did an association study, using a canine SNP chip similar to the feline one discussed above. She used the chip to compare the SNPs found in individual dogs from various breeds, and looked for correlations between the average breed behaviors and the SNPs that she found in individuals of those breeds.

She had some interesting results which will benefit from more study. For example, for the behavior of urinating while left alone, she found an association in an area which is related to behavioral disorders in humans. Finding this association in an area which seems to affect behavior suggested to her that she might be on the right track, though of course a lot more work will need to be done. She mentioned some other interesting associations that she found as well. She also, of course, found associations that appear spurious, such as the association between a gene for long hair and chasing behavior. One amusing association she found was a relationship between the gene for short legs, such as you might see in a corgi, and a fear of stairs! She commented that sometimes physical traits explain behavior.

...And that is my smattering of summaries from the conference. Here’s hoping that I will manage to attend the next one, in eighteen months, in the other Cambridge — the one in the UK!

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