Cause of Rare and Fatal Dog Disease Pinpointed

A healthy Brazilian Terrier puppy (right) and a puppy affected by a severe skeletal disorder that makes standing and walking impossible. CREDIT: Professor Hannes Lohi View full size image

A rare but fatal skeletal disease in dogs has been traced to a single gene mutation, offering hope that the condition could be treated or eliminated by smart breeding.

A similar condition affects humans, researchers reported July 5 in the journal PLoS ONE. That means developing a cure in dogs could help people with the condition.

The bone disorder, called mucopolysaccharidoses, affects a rare breed of dog called the Brazilian terrier. These dogs, also called Fox Paulistinhas, were first bred from native Brazilian dogs and terriers from Europe. The breed is almost unknown outside of Brazil and Finland.

A tragic disorder

In rare cases, Brazilian terriers are born with a mysterious bone disease that deforms their skeleton, leaving them unable to stand or walk. These puppies fail to thrive, and either die or have to be euthanized. Researchers at the University of Helsinki wanted to find out why. [What Your Dog's Breed Says About You]

Led by researcher Hannes Lohi of the University of Helsinki and the Folkhalsan Research Center, the scientists delved into the Brazilian terrier genome in search of mutations that could be to blame for the disease. They compared seven affected and 11 unaffected terriers, eventually narrowing the search down to a stretch of genes on the sixth chromosome.

Chromosomes are coils of DNA passed down to offspring from parents. Humans have 46 total chromosomes. Dogs have 78.

The section of chromosome 6 that Lohi and his colleagues targeted had more than 220 genes, a huge number to analyze by traditional methods. Instead, the researchers turned to a new approach.

"Instead of analyzing the region gene by gene, we were able to capture and read the entire region simultaneously in the selected samples," Lohi said in a statement. "The mutation was quickly discovered and subsequently confirmed in over 200 dogs."

Identifying a mutation

The mutation, the researchers discovered, occurred in a gene called GUSB. This mutation causes a change in one of the amino acid molecules that makes up an important enzyme for proper bone growth and formation. Without the enzyme, the body is unable to effectively "clean up" the connective tissue in the bones, meaning it can't sweep away damaged cellular detritus or foreign bacteria.

Mucopolysaccharidoses is not confined to dogs. Mice, cats and even humans have similar disorders. In humans, symptoms typically include skeletal deformities, mental retardation and abnormal enlargement of the spleen and liver.

Almost every third Brazilian terrier carries the mutation, the researchers found. To be affected by the disease, however, puppies have to inherit two copies of the bad gene, one from their father and one from their mother. Lohi and his colleagues developed a genetic test for breeders to test their sires and dams for the mutation in order to ensure that two carriers aren't allowed to mate and have puppies.

Studies on dog genetics are also useful for studying rare diseases in humans, the researchers wrote. Thanks to genetic similarities between dogs and humans, our canine companions are already used as guinea pigs in cancer research, getting experimental treatments before they're approved for humans. 

Follow Stephanie Pappas on Twitter @sipappas or LiveScience @livescience. We're also on Facebook & Google+.