For thousands of years the dog has been humanity’s best friend. Long before we tamed the horse or invented agriculture, we domesticated the dog. As we spread throughout the world, the dog paced at our heels. And yet for all the centuries of adventure and perils we shared, much about dogs remains a mystery. How did the wolf, with its fairly uniform phenotype and behavior, become the dog with its diverse shapes, sizes, colors, and abilities? What genes control those changes, and what can we learn about evolution and about ourselves through looking at the dog genome?
Adam R. Boyko, Biomedical Sciences, is searching for the answers through a series of research projects on the canine genome. Lately, a big chunk of his work has focused on canines that live around human settlements but are not pets. Known as village dogs, they are essentially left to their own devices to survive. “There are a billion dogs in the world, and the vast majority are these natural populations of village dogs,” says Boyko. “From a research standpoint, hardly anyone had even looked at them before.” Boyko and his lab took saliva and blood samples from 550 village dogs around the world, along with many purebred samples, and ran genome sequencing. Then they compared the results to make inferences about canine heredity and origins.
Studying Dogs’ Barcodes
The canine genome is comprised of roughly three billion base pairs made up of four nucleotides, the units typically scrutinized in genetic studies. Rather than looking at the entire genome for every dog in the study, Boyko’s lab has designed a research-grade genotyping microarray, or chip, that targets 215,000 base-pair sites on the genome that are particularly important. “When you’re doing DNA sequencing, 99.9 percent of the genome is the same between two individuals, so you’re wasting a lot of time looking at everything,” Boyko says. “It’s much more cost effective to concentrate on parts of the genome where there is variation.”
The researchers zeroed in on specific stretches of chromosomes called haplotypes—a series of alleles (variant forms of given genes) that were inherited together from the same parent and are present on the same chromosome copy across the species. A haplotype can be characterized by its sequence of nucleotides and by other factors that essentially create a barcode for that stretch of the chromosome in that individual. “We can take that barcode and see if it shows up in that same region in other dog populations,” says Boyko. “If it does, we know those populations inherited that barcode from a common ancestor, and then we can start to understand how different populations are related.”
Dogs and Humans
Using this technique Boyko found there was more genetic diversity in village dogs than in purebreds and that, among all village dogs, the highest genetic diversity was in Central Asia, which implies that is where dogs were first domesticated about 15,000 to 20,000 years ago. “The earliest archeological remains of dogs aren’t in Central Asia,” Boyko explains, “but the genomic diversity signature is homing in on Asia. It’s a matter of getting more samples to figure out where exactly in Asia the origin of the domestic dog lies.”
“That data is useful not just to tell owners things about their dogs that we already know, but also to help build the database that researchers need to make new discoveries tomorrow.”
Boyko’s genomic research also brings ever-increasing understanding of the mechanisms of dogs’ inheritance, including shedding light on the role genes play in disease and longevity. Many of these findings can be extrapolated to humans as well. “Dogs are a great model species for humans,” Boyko says. “They live in human environments and they’re getting diagnosed with the same disorders that people are. So a lot of dog diseases have analogous human disorders, and it turns out when you identify the mutation causing the disease in dogs, it’s the same genes or the same pathways in humans that are mutated and causing the disease. When you look at purebred dogs, the breeds are small populations with closed genetics. That simplifies the associations between genes and disease, and we can identify them much more rapidly than in humans.”
Embark’s Dog DNA Home Test Kit and the Cornell Canine Biobank
As an offshoot of Boyko’s research on canine genomic testing, he has cofounded a company called Embark with his brother, Ryan Boyko. The company is part of Cornell’s life science incubator, the Kevin M. McGovern Family Center for Venture Development in the Life Sciences. Embark’s product is a test for dogs based on the Boyko Lab’s invention of the research-grade genotyping chip. The test comes in a simple kit that dog owners can purchase for home use. “There are other dog DNA tests, but they’re are not using research-grade chips,” says Boyko, who is the company’s chief science officer. “At most, they are typing dogs at 1,800 markers. Our test is over one hundred times bigger.”
Customers get detailed results about their dogs that pinpoint things like genealogy by breed (going back for four generations, which is especially useful if the test dog is a mixed breed), size and weight at adulthood, percentage of wolf DNA (most dogs have about one percent wolf, although some can have as much as five percent), and genetic predisposition for certain diseases. “We’ve just rolled out a research feature,” Boyko explains. “Customers can opt to take part in the research and fill out questionnaires. We want to know about nutrition and exercise and whether their dog is allergic. We plan to compare allergy profiles to genetic profiles to determine the genetics of allergies.”
As customers send in the samples of their dogs’ DNA to Embark, Boyko will add them to the Cornell canine biobank. “In order to understand things like dog cancer or behavior or those sorts of complicated things, you really do need thousands and thousands of dogs in your study,” Boyko says. “If owners and veterinarians can be convinced of the value of testing dogs on research-grade chips instead of smaller testing panels, then we will have created this research resource that’s never existed before. That data is useful not just to tell owners things about their dogs that we already know, but also to help build the database that researchers need to make new discoveries tomorrow.”