The Wisdom Panel™ team recently completed research on a condition called cryptorchidism. Known in layman’s terms as “undescended testicles,” cryptorchidism is the failure of one or both testicles to drop into the scrotal sac during development.
The retained testicle(s) may stay trapped in the inner groin area—known technically as the inguinal canal—or the abdomen. Right-sided inguinal cryptorchidism is the most common, followed by right-sided abdominal. It’s rare to see both testicles retained.
A few facts about cryptorchidism
Before we get into our research, it’s helpful to understand why this condition is of interest and how it can impact a dog’s health. So let’s shed a little more light on cryptorchidism in general.
- Cryptorchid testicles cannot produce sperm.
- The rate of testicular tumors is 13 times higher in cryptorchid testicles.
- The most common type of tumor in the cryptorchid testicle is called a Sertoli cell tumor. This type of tumor can cause bone marrow suppression, which can be life-threatening.
- Testicular torsion (twisting) is more common in cryptorchid dogs and is a painful medical emergency.
- Neutering a cryptorchid dog is a more complicated surgery than a “normal” neuter. It costs more, the pup is under anesthesia for longer, and there is an increased risk of complications.
- Cryptorchidism is also common in boys. Dogs can help us study the condition so we can make advancements in human medicine as well.
Overview of the research
Wisdom Panel scientists partnered with Banfield Pet Hospital® to study the genetic component behind cryptorchidism.
To start, we gathered data from 3,736 dogs with inguinal cryptorchidism and an equal number of healthy, unaffected controls. We then ran a genome-wide association study, or GWAS, to see if we could find regions of the genome that are specifically linked to an increased propensity for cryptorchidism.
What is a GWAS? The National Human Genome Research Group defines a GWAS as “a research approach used to identify genomic variants that are statistically associated with a risk for a disease or a particular trait. The method involves surveying the DNA code of many people (or dogs!) and looking for variants that occur more frequently in those with a specific disease or trait compared to those without the disease or trait. Once such genomic variants are identified, they are typically used to search for nearby variants that contribute directly to the disease or trait.”
A quick look at our findings
Our team discovered a so-called peak (signal of association) on canine chromosome 10, with its top marker located in a gene called HMGA2, showing a significant association with the cryptorchid cases in the study. As we dug deeper, we found that genetic variation in the identified gene likely increases a dog’s risk of cryptorchidism.
Interestingly, the HMGA2 gene is also associated with smaller size in the dog. This finding aligns with the fact that smaller versions of breeds (for example, the toy, miniature, and standard Poodle) are more likely to be cryptorchid than their larger counterparts.
In addition to the discovery of a genetic risk variant for canine cryptorchidism, this study demonstrates the power of using big data for genetic discovery, particularly in complex disorders with onset influenced by both genetic and environmental factors. Hopefully, this approach will lead to further understanding of the underpinnings of complex disease in dogs and people.