Canine research is a promising field, aiming to address basic biological and medical questions about dogs and humans alike. Central to these efforts are modern genomic tools, which enable extensive comparisons between individual genomes to identify the sources of traits and conditions and suggest possible avenues for treatment. Dr. Elinor K. Karlsson has asked and answered important questions about dogs with her canine research program, including questions that involved getting the public to share their pet information.
Humans have selectively bred dogs for coexistence with humans for thousands of years, since long before the invention of cities or the wheel. Dogs are thus uniquely responsive to human social cues, and many of their behaviors are familiar and recognizable to humans where related behaviors in other mammals are not. Relatedly, the selective breeding of dogs has included encouraging different behavior patterns in different breeds, creating ready-made research populations for studying those behaviors and identifying their genetic roots. The genetic bases of canine behavior have much in common with those of human behavior, therefore, canine research has the potential to improve the lot of both humans and dogs as it advances. Dogs are also abundant and widespread in human society, making them ideal subjects for citizen science, wherein non-scientists collect data and pass it on to scientists to examine and process.
Dr. Karlsson has successfully identified genes related to canine obsessive-compulsive disorder (OCD) in doberman pinschers.1 Canine OCD is highly heritable, making it an ideal candidate for genomic research. Dr. Karlsson and her colleagues used gene arrays to compare dobermans with and without OCD symptoms, and identified a gene also implicated in human OCD whose protein product stabilizes connections between glutaminergic neurons. However, this study was limited both by the available gene arrays and by the study animals. Dog breeds are highly inbred populations, which is often advantageous for studies about very specific differences, but in this case also obscured part of the OCD story. Many genes already identified in humans and in other dog breeds as being related to OCD were not accessible to this study, because the doberman population exhibited no variation at these loci.
Getting a clearer picture of canine genetics would require data on a much more diverse set of dogs, including mixed-breed dogs. Such a diverse study population would have to be much larger, to make sure that any variation detected was not a false positive. To be sure to detect important signals, the information on each dog would have to be at least as thorough as it was for the studies on smaller numbers of purebred animals. Getting access to information on that many dogs was itself a challenge, so Dr. Karlsson established the citizen-science initiative Darwin’s Dogs, inviting the public to submit canine cheek swabs and behavioral questionnaires about their pets of any and no pedigree. Darwin’s Dogs collected information on nearly 15,000 dogs, an enormous sample size that has enabled exceptionally detailed research. Sequencing each of those genomes would have been prohibitively expensive, even with the cost of whole-genome sequencing declining every year, but most canine gene arrays did not offer the level of detail required to take proper advantage of this enormous data set. Dr. Karlsson addressed this conundrum with Applied Biosystems Axiom Canine Genotyping Arrays.
The Axiom Canine HD Array enables analysis of over 710,000 markers, including breed-specific markers, disease markers, and genetic signatures from older gene panels, as well as the latest identified insights from the CanFam3 reference genome. Developed by screening over 2,000 samples covering 50 breeds using the Axiom Canine Genotyping Arrays Sets A and B, carefully selected with appropriate pedigree to maximize polymorphic content, the Axiom Canine HD array reduces the expertise and time needed to succeed at canine genetics research. Dr. Karlsson emphasizes that “The array gives us much more information about the genetics of each individual dog,” and, “For each individual dog, it doesn’t cost us as much as getting a whole genome sequence.” As she further explains, “This array combines the power of large sample size and dense information. We’re now going to be able to find things that we couldn’t find if we didn’t have that combination of factors.”
Additionally, the Axiom platform features a variety of analysis tools that enable research into heterozygosity loss, copy number detection, and other advanced genetics information. Such information is increasingly important in disease biology, for both human and canine subjects, particularly in the context of cancer, and of extreme traits driven by additional copies of otherwise ordinary genes. The possibilities enabled by the Axiom Canine Arrays have opened up new research areas for Dr. Karlsson’s lab. With such ready access to dense data sets about individual dogs’ genetics, she and her colleagues can undertake studies of additional conditions and even create detailed ancestry reports for individual mixed-breed dogs.
Dr. Karlsson discusses her research and the role of the Axiom Canine Genotyping Array in her work in her PAG workshop.
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1. Dodman, N. H., et al. (2010) “A canine chromosome 7 locus confers compulsive disorder susceptibility,” Molecular Psychiatry 15(1) (pp. 8-10)
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