Gencove Team - Apr 22, 2024

Leading the pack: Low-pass plus capture as the next great tool for canine genomics

Dog research is at a crossroads. Like in humans, genetic tools could revolutionize veterinary care and improve the health and welfare of all dogs, but widely used genetic testing services don’t provide the information needed by researchers to achieve this vision. A collaboration between Gencove, genomic scientists, and dog breeders has developed a new solution that combines high-accuracy genetic testing with comprehensive whole genome genotyping. This dual-purpose product supports breed ancestry analysis, Mendelian disease testing, and large-scale genomics.

Dog owners, veterinarians, and researchers today are increasingly curious about breed characteristics and how variants in their DNA may affect their health. Recognizing the prevalence of Mendelian diseases among canines, there is a growing demand for sophisticated genotyping solutions that go beyond basic breed identification, that address known health risks, and that allow for improving our understanding of how specific variants have differential effects in different breeds, mixed ancestry, or non-breed dogs.

Current Genotyping Approaches in Canines
Traditional dog genotyping methods primarily use fixed arrays that lack the flexibility to incorporate new traits and to better refine our genetic understanding of existing traits. This method constrains both researchers and the dog genetics industry, preventing them from accessing the most up-to-date information about potential genetic health issues.

Low-pass whole genome sequencing has become a crucial tool in canine research, providing a cost-effective method for obtaining broad genetic insights across entire genomes. This approach allows for the identification of genetic variants and their associations with various traits and diseases at a fraction of the cost of high-depth sequencing. Low-pass sequencing has provided the foundation of quantitative trait genetics for citizen science, enabling the scale and resolution needed to identify QTLs (Figure 1).

An Optimized Approach: Low-Pass WGS Plus Target Capture
For several years and for several species, Gencove has been extending the use of low-pass with the addition of target capture. We are delighted to launch our first implementation of this tool in canines. This dual method not only allows for broad genotyping but also focuses on high-coverage regions of particular interest. It's a simple, cost-effective strategy that yields highly accurate genome-wide information from a single technology.

Collaborative Development and Validation
To advance this technology, Gencove has partnered with the Karlsson Lab at the Broad Institute to develop a public capture panel specifically designed for canine genotyping in clinical and research settings. This panel targets 185 SNPs & small indels curated by the Karlsson Lab for a wide variety of publicly researched diseases and conditions. The effectiveness of this method was validated through the sequencing of 190 single-breed and mixed ancestry dogs, achieving over 200x coverage at targeted sites. We still are able to deliver low-pass that produces over 35 million SNPs and 15 million indels.

Our validation process included genotype accuracy assessments for specific visual traits, such as the FGF4L2 gene on CFA12, which is associated with short limbs and intervertebral disc disease (IVDD) risk (Brown et al., 2017). Results confirmed the high prevalence of FGF4L2 carriers in breeds like corgis, dachshunds, beagles, and spaniels, demonstrating the method's precision (Figure 2). Capture can be used for characterization of an allele associated with complex traits like chondrodystrophy caused by retrogenes. With appropriate training data, these tools can be deployed in diverse population backgrounds.

Beyond Simple Screening: Comprehensive Health Insights
Adopting low-pass WGS coupled with targeted capture allows dog owners to capture a detailed picture of their animal's health that transcends mere breed analysis. It opens up possibilities for proactive health management, including diet and lifestyle adjustments and preemptive medical measures. Owners can become aware of their dogs' potential for drug sensitivities, degenerative diseases, and bleeding tendencies, among other conditions. Capture can be adapted to a wide variety of diseases that affect dog breeds today.

Research and Clinical Applications
This technology is not just for pet owners, breeders and clinicians but is also a powerful tool for researchers. It facilitates the discovery of novel alleles and better resolution of complex regions. This adaptability makes it an invaluable addition to clinical genotyping programs, especially those tailored to specific traits or diseases.

This target capture panel, particularly when coupled with low-pass WGS, offers a significant leap forward in cost-effective and high-throughput canine genotyping. It combines comprehensive genomic insights with a flexible, accurate, and straightforward process that can easily integrate into existing workflows. This advancement not only enhances our understanding of canine genetics but also improves the quality of life for our dogs by enabling informed decisions about their health care. Get in touch to learn more about how we can customize the approach to the specific needs of your dog population, to drive both health and scientific breakthroughs in canines.