Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats

In the largest DNA-based study of domestic cats to date, 11,036 individuals (10,419 pedigreed cats and 617 non-pedigreed cats) were genotyped via commercial panel testing elucidating the distribution and frequency of known disease, blood type, and physical trait associated genetic variants across cat breeds. This study provides allele frequencies for many disease-associated variants for the first time and provides updates on previously reported information with evidence suggesting that DNA testing has been effectively used to reduce disease associated variants within certain pedigreed cat populations over time. We identified 13 disease-associated variants in 47 breeds or breed types in which the variant had not previously been documented, highlighting the relevance of comprehensive genetic screening across breeds. Three disease-associated variants were discovered in non-pedigreed cats only. To investigate the causality of nine disease-associated variants in cats of different breed backgrounds our veterinarians conducted owner interviews, reviewed clinical records, and invited cats to have follow-up clinical examinations. Additionally, genetic variants determining blood types A, B and AB, which are relevant clinically and in cat breeding, were genotyped. Appearance-associated genetic variation in all cats is also discussed. Lastly, genome-wide SNP heterozygosity levels were calculated to obtain a comparable measure of the genetic diversity in different cat breeds. This study represents the first comprehensive exploration of informative Mendelian variants in felines by screening over 10,000 pedigreed cats. The results qualitatively contribute to the understanding of feline variant heritage and genetic diversity and demonstrate the clinical utility and importance of such information in supporting breeding programs and the research community. The work also highlights the crucial commitment of pedigreed cat breeders and registries in supporting the establishment of large genomic databases, that when combined with phenotype information can advance scientific understanding and provide insights that can be applied to improve the health and welfare of cats. Author summaryDomestic cats are one of the world's most popular companion animals, of which pedigreed cats represent small unique subpopulations. Genetic research on pedigreed cats has facilitated discoveries of heritable conditions resulting in the availability of DNA testing for studying and managing inherited disorders and traits in specific cat breeds. We have explored an extensive study cohort of 11,036 domestic cat samples representing pedigreed cats of 90 breeds and breed types. This work provided insight into the heritage of feline disease and trait alleles. We gained knowledge on the most common and relevant genetic markers for inherited disorders and physical traits, and the genetic determinants of the clinically relevant AB blood group system. We also used a measure of genetic diversity to compare inbreeding levels within and between breeds. This information can help support sustainable breeding goals within the cat fancy. Direct-to-consumer genetic tests help to raise awareness of various inherited single gene conditions in cats and provide information that owners can share with their veterinarians. In due course, ventures of this type will enable the genetics of common complex feline disease to be deciphered, paving the way for precision healthcare with the potential to ultimately improve welfare for all cats.Peer reviewe