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

Abstract

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.

Dystrophin (DMD) Missense Variant in Cats with Becker-Type Muscular Dystrophy

“…Compared to the healthy appearing littermates, the two affected males appeared to have longer hair coats, bushy tails, and ear tufts suggesting Maine Coon breed ancestry. The results of a commercial feline DNA panel of cat #1 revealed a 26% Maine Coon contribution, a blood type A by CMAH genotyping, and no known disease-causing variants tested for (Mars Veterinary, Portland, OR, USA) [ 39 , 40 ]. The conditions of both affected males only marginally progressed clinically, and the two healthy appearing littermates as well as the litter’s queen also remained unchanged over the eight-month observation period.…”

“…The tom of the litter and mother of the queen were not available for genotyping. The queen as well as affected males had features of the Maine Coon breed, and indeed cat #1 had 26% SNV alleles seen in Maine Coon cats [ 39 ]. The other littermates appeared more like regular domestic shorthair cats.…”

“…The molecular genetic studies with DNA samples were part of an approved research study (the Cantonal Committee for Animal Experiments Bern; permit BE 71/19). Routine physical and cardiac examinations, hematology and serum chemistry tests, as well genetic testing for breed, hereditary disease, and other genetic traits (e.g, ABC blood typing) (Mars Veterinary, Portland, OR, USA) [ 39 ], were performed.…”

“…In addition, archived genomic DNA samples from 597 domestic cats without evidence of muscular dystrophy of different breeds from the Vetsuisse Biobank were screened for the herein discovered DMD missense variant. Cheek swabs were used for commercial feline genetic marker screening (Mars Veterinary, Portland, OR, USA) [ 39 ].…”

Dystrophin (DMD) missense variant in cats with Becker type muscular dystrophy

“…Compared to the healthy appearing littermates, the two affected males appeared to have longer hair coats, bushy tails, and ear tufts suggesting Maine Coon breed ancestry. The results of a commercial feline DNA panel of cat #1 revealed a 26% Maine Coon contribution, a blood type A by CMAH genotyping, and no known disease-causing variants tested for (Mars Veterinary, Portland, OR, USA) [39,40]. The conditions of both affected males only marginally progressed clinically, and the two healthy appearing littermates as well as the litter's queen also remained unchanged over the eight-month observation period.…”