Another Step Toward Genomics Medicine for Cats

Crowned the French people’s favorite pet in 2017, the cat both fascinates and inspires. With some 14 million cats, France has the second-largest feline population in Europe. And that means just as many mouths to feed as there are furballs to care for. A new form of precision veterinary medicine is emerging: genomics. Its integration into clinical practice will have a substantial impact on the health of pets.   Genomics has fundamentally transformed the conduct of biomedical research and the care of human patients. By identifying individuals’ genetic predispositions, it enables better diagnosis and more effective treatment—with fewer side effects—of diseases at an early stage, as well as the prevention of more severe symptoms. Its applications in the animal world could significantly improve veterinary medicine. However, for technical and financial reasons, genomics has been slow to be integrated into veterinary medicine. Indeed, genomics medicine relies on advanced knowledge of intraspecies genetic variations and the ability to sequence individual genomes within a limited timeframe and at a moderate cost before genomic information can be interpreted in a medical context. Before this practice becomes routine in cats, we must therefore first expand our knowledge of feline genomics variants, such as single nucleotide variants (SNVs) and structural variants (SVs). This represents a huge challenge, but progress in this field has recently accelerated, particularly with the development of high-throughput sequencing technologies. To date, at least 70 genes have been identified in cats that harbor single and multiple DNA variants associated with diseases such as cardiomyopathy, retinal degeneration, and polycystic kidney disease. The genetic and clinical manifestations of most known variants are described in the Online Mendelian Inheritance in Animals database. However, discoveries of genetic variation in cats are limited by fragmentation in the genomics assembly. There is a lack of a complete, high-quality reference genome with sufficient sequencing depth to identify rare alleles and interpret complex structural variants associated with feline diseases. The current reference contains more than 300,000 gaps, whereas new genomics mapping technologies have been able to create much more complete genomics representations for many other species. Researchers therefore set out to assemble Felis_catus_9.0, a new domestic cat genomics reference, using long PacBio read sequences that significantly improve sequence coverage and the contiguity of the assembly. The genomics sequences of 54 domestic cats were aligned to the reference to identify SNVs and SVs. Numerous causative mutations responsible for diseases, particularly cancers, were identified in this way. Among these is an SV in the UGDH gene linked to feline dwarfism but not human dwarfism, which could therefore shed light on undiagnosed cases of dwarfism in humans. This new feline genomics assembly is a powerful resource not only for the discovery of new feline and human traits, but also for the future practice of feline genomics medicine, which is expected to emerge soon.