P6046 Precision medicine and the 99 Lives Cat Genome Sequencing Initiative

Abstract

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Precision medicine gives clinicians tools to better understand the complex mechanisms underlying a patient’s health, disease, or condition, and to better predict which treatments will be most effective. Overall, an individual’s specific genetic makeup will become an intricate part of their standard health care. The 99 Lives Cat Genome Sequencing Initiative is developing the cat genome DNA variant database to apply precision medicine to cats. To date, the 20 to 30× whole genome sequences (WGS) of 73 domestic cats from different breeds and populations and nine wild felids including, three black-footed cats (Felis nigripes) and one Pallas cat (Otocolobus manul) are included. Maverix Biomics (San Mateo, CA) provides the variant calling and a web-based interface for filtering for specific cats and variants types in a given analysis. Over two dozen researchers and veterinarians have participated worldwide. Several successes have been demonstrated for the project in the past 2 yr. The causal genes and variants for three inherited retinal degenerations have been identified in Persian, Bengal, and black-footed cats. A new variant in PKD1 has been identified in the Pallas cat with renal disease, further demonstrating the power of cross-species analyses. Sequencing of an affected sibpair led to the discovery of the variant causing an immuno-lymphoproliferative disease in British Shorthair cats. A single cat with GWAS localization of disease was sequenced, identifying the variant in COLQ for congenital Myasthenic syndrome in Devon rex. Recently, a patient was presented to the University of Missouri, Veterinary Health Center. The cat was diagnosed with an undefined but potential lysosomal storage disease. WGS of this individual patient identified a homozygous and unique variant in the gene for Niemann-Pick Type 1 (NPC1). NPC1 has been previously identified in cats; however, the variant in this singleton cat is novel. Although NPC1 has no effective treatment, if additional cats are identified, they could further develop gene therapies and treatments for the disease. The variants identified for disease in the wild felids suggest DNA testing is required for proper management in their captive breeding, species survival plans. The 99 Lives project has proven successful within and across felid species, including analyses of diseases with and without a priori genetic localization.