Demographics of hip dysplasia in the Maine Coon cat

Objectives The aim of this study was to report the demographics of feline hip dysplasia (FHD) in the Maine Coon cat. Methods The complete hip dysplasia registry (public and private) collected by the Orthopedic Foundation for Animals through April 2015 was accessed. There were 2732 unique cats; 2708 (99.1%) were Maine Coons, and only these were studied. Variables analyzed were sex, month/season of birth and hip dysplasia score. Two groups were created: those with and without FHD. P <0.05 was considered statistically significant. Results The youngest cat with FHD was 4 months of age. The majority of the radiographs (2604/2708 [96.2%]) were performed between 4 and 60 months of age. Non-borderline scores for these 2604 cats were available in 2548, and were the data used for this study. The overall prevalence of FHD was 24.9% (635/2548), and was slightly higher in males (279/1023 [27.3%]) than females (356/1525 [23.3%]) (P = 0.025). Those with more severe dysplasia were older. The percentage of bilateral FHD was 56%, and bilateral cases had more severe dysplasia than unilateral cases but with no age difference. Month/season of birth or geographic region of origin did not influence the prevalence of FHD. Conclusions and relevance This is the largest demographic study of FHD in the Maine Coon cat. The overall prevalence in the Orthopedic Foundation for Animals registry was 24.9%, and slightly higher in males (27.3%) than females (23.3%). Dysplasia was more severe in bilateral than unilateral cases and with increasing age. Caution should be used when extrapolating these findings to other feline breeds or other groups of Maine Coon cats. Further studies need to be performed among other breeds and geographic locations to better understand the demographics of feline hip dysplasia

Acute synovitis and intra-articular methylprednisolone acetate in ponies

AbstractObjective: To determine how acute synovitis, with and without intra-articular methylprednisolone acetate (MPA), affect synthesis of proteoglycan, total protein, and collagen in articular cartilage and total protein synthesis in synovial membrane.Design: Synovitis was induced in 10 ponies by the injection of 0.5 ng lipopolysaccharide (LPS) into the left radiocarpal and midcarpal joints every 2 days for a total of four treatments. Synovitis was documented by clinical examination and synovial fluid analyses. Two days before euthanasia, MPA (0.1 mg/kg) was injected with the last dose of LPS into both the left and right radiocarpal and midcarpal joints of five of these ponies. Proteoglycan synthesis in articular cartilage explants from these joints was measured by incorporation of sodium [35S]sulfate. The size of the proteoglycan monomers and their aggregation with hyaluronan was assessed by size-exclusion chromatography. Protein synthesis in articular cartilage was measured by incorporation of [3H]proline and collagen synthesis by conversion of [3H]proline into [3H]hydroxyproline. Protein synthesis was measured in synovial membrane explants by incorporation of [35S]methionine.Results: Ponies developed carpal effusion and mild lameness accompanied by increased total nucleated cell count and total solids in synovial fluid in response to the LPS injections. Moderate to severe synovial membrane proliferation and inflammation were observed histopathologically in joints injected with LPS but no consistent light-microscopical changes were observed in the articular cartilage from these joints. Intra-articular MPA alone was associated with decreased proteoglycan synthesis and increased protein and collagen synthesis in the cartilage explants. Total protein synthesis by synovial membrane was also increased by MPA alone. In contrast, no differences in protein or proteoglycan synthesis were observed in explants from the joints with synovitis, with or without intra-articular MPA. Treatment with MPA, LPS, and LPS/MPA did not alter proteoglycan aggregate size, but LPS-induced synovitis resulted in an increase in the second largest population of monomers. MPA increased the synthesis of small proteoglycan monomers.Conclusion: Based on the methods used, acute synovitis prevented changes induced by intra-articular MPA alone. Results suggested that the effect of intra-articular MPA on joint metabolism was different between inflamed and normal joints. Experimental studies must consider the effect of inflammation, as well as the potential to introducein vitroculture artifacts when investigating the effect of intra-articular corticosteroids on chondrocyte function

Joint genomic prediction of canine hip dysplasia in UK and US Labrador Retrievers

Canine hip dysplasia, a debilitating orthopedic disorder that leads to osteoarthritis and cartilage degeneration, is common in several large-sized dog breeds and shows moderate heritability suggesting that selection can reduce prevalence. Estimating genomic breeding values require large reference populations, which are expensive to genotype for development of genomic prediction tools. Combining datasets from different countries could be an option to help build larger reference datasets without incurring extra genotyping costs. Our objective was to evaluate genomic prediction based on a combination of UK and US datasets of genotyped dogs with records of Norberg angle scores, related to canine hip dysplasia. Prediction accuracies using a single population were 0.179 and 0.290 for 1,179 and 242 UK and US Labrador Retrievers, respectively. Prediction accuracies changed to 0.189 and 0.260, with an increased bias of genomic breeding values when using a joint training set (biased upwards for the US population and downwards for the UK population). Our results show that in this study of canine hip dysplasia, little or no benefit was gained from using a joint training set as compared to using a single population as training set. We attribute this to differences in the genetic background of the two populations as well as the small sample size of the US dataset

Mixed linear model approach adapted for genome-wide association studies.

5 5 t e c h n i c a l r e p o r t s Mixed linear model (MLM) methods have proven useful in controlling for population structure and relatedness within genome-wide association studies. However, MLM-based methods can be computationally challenging for large datasets. We report a compression approach, called &apos;compressed MLM&apos;, that decreases the effective sample size of such datasets by clustering individuals into groups. We also present a complementary approach, &apos;population parameters previously determined&apos; (P3D), that eliminates the need to re-compute variance components. We applied these two methods both independently and combined in selected genetic association datasets from human, dog and maize. The joint implementation of these two methods markedly reduced computing time and either maintained or improved statistical power. We used simulations to demonstrate the usefulness in controlling for substructure in genetic association datasets for a range of species and genetic architectures. We have made these methods available within an implementation of the software program TASSEL. Although genome-wide association studies (GWAS) have the potential to pinpoint genetic polymorphisms underlying human diseases and agriculturally important traits, false discoveries are a major concern 1 and can be partially attributed to spurious associations caused by population structure and unequal relatedness among individuals in a given cohort. Population stratification was initially addressed using general linear model (GLM)-based methods such as structured association 2 , genomic control 3 and family-based tests of association 4 . The introduction of MLM approaches has more recently been demonstrated as an improved method to simultaneously account for population structure and unequal relatedness among individuals 5 . In the MLM-based methods, population structure 2,6 is fit as a fixed effect, whereas kinship among individuals is incorporated as the variance-covariance structure of the random effect for the individuals. Regardless of the applied statistical method, GWAS require large sample sizes to achieve sufficient statistical power 7 , especially in order to detect the small effect polymorphisms that underlie most complex traits 8 . For the MLM approach, datasets with these large sample sizes create a heavy computational burden because the computing time for solving a MLM increases with the cube of the number of individuals fit as a random effect. The earliest effort to reduce the size of the random effect in an MLM can be traced back to the sire model approach used in animal breeding 9-12 , which replaces an individual&apos;s genetic effect with that of its sire. Consequently, the sire-model approach requires pedigrees, which are not always available, and which in particular are often not available in plant studies. Even with available pedigrees, the use of a marker-based kinship is preferred because of its higher accurac

Early-onset progressive retinal atrophy associated with an IQCB1 variant in African black-footed cats (Felis nigripes)

African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management

Precision medicine in cats:novel niemann-pick type C1 diagnosed by whole-genome sequencing

State-of-the-art health care includes genome sequencing of the patient to identify genetic variants that contribute to either the cause of their malady or variants that can be targeted to improve treatment. The goal was to introduce state-of-the-art health care to cats using genomics and a precision medicine approach. To test the feasibility of a precision medicine approach in domestic cats, a single cat that presented to the University of Missouri, Veterinary Health Center with an undiagnosed neurologic disease was whole-genome sequenced. The DNA variants from the cat were compared to the DNA variant database produced by the 99 Lives Cat Genome Sequencing Consortium. Approximately 25× genomic coverage was produced for the cat. A predicted p.H441P missense mutation was identified in NPC1, the gene causing Niemann-Pick type C1 on cat chromosome D3.47456793 caused by an adenine-to-cytosine transversion, c.1322A>C. The cat was homozygous for the variant. The variant was not identified in any other 73 domestic and 9 wild felids in the sequence database or 190 additionally genotyped cats of various breeds. The successful effort suggested precision medicine is feasible for cats and other undiagnosed cats may benefit from a genomic analysis approach. The 99 Lives DNA variant database was sufficient but would benefit from additional cat sequences. Other cats with the mutation may be identified and could be introduced as a new biomedical model for NPC1. A genetic test could eliminate the disease variant from the population

A deletion in GDF7 is associated with a heritable forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts in cats

Publisher Copyright: © 2020 by the authors.An inherited neurologic syndrome in a family of mixed-breed Oriental cats has been characterized as forebrain commissural malformation, concurrent with ventriculomegaly and interhemispheric cysts. However, the genetic basis for this autosomal recessive syndrome in cats is unknown. Forty-three cats were genotyped on the Illumina Infinium Feline 63K iSelect DNA Array and used for analyses. Genome-wide association studies, including a sib-transmission disequilibrium test and a case-control association analysis, and homozygosity mapping, identified a critical region on cat chromosome A3. Short-read whole genome sequencing was completed for a cat trio segregating with the syndrome. A homozygous 7 bp deletion in growth differentiation factor 7 (GDF7) (c.221_227delGCCGCGC [p.Arg74Profs]) was identified in affected cats, by comparison to the 99 Lives Cat variant dataset, validated using Sanger sequencing and genotyped by fragment analyses. This variant was not identified in 192 unaffected cats in the 99 Lives dataset. The variant segregated concordantly in an extended pedigree. In mice, GDF7 mRNA is expressed within the roof plate when commissural axons initiate ventrally-directed growth. This finding emphasized the importance of GDF7 in the neurodevelopmental process in the mammalian brain. A genetic test can be developed for use by cat breeders to eradicate this variant.Peer reviewe

Werewolf, there wolf : Variants in hairless associated with hypotrichia and roaning in the lykoi cat breed

Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.A variety of cat breeds have been developed via novelty selection on aesthetic, dermatological traits, such as coat colors and fur types. A recently developed breed, the lykoi (a.k.a. werewolf cat), was bred from cats with a sparse hair coat with roaning, implying full color and all white hairs. The lykoi phenotype is a form of hypotrichia, presenting as a significant reduction in the average numbers of follicles per hair follicle group as compared to domestic shorthair cats, a mild to severe perifollicular to mural lymphocytic infiltration in 77% of observed hair follicle groups, and the follicles are often miniaturized, dilated, and dysplastic. Whole genome sequencing was conducted on a single lykoi cat that was a cross between two independently ascertained lineages. Comparison to the 99 Lives dataset of 194 non‐lykoi cats suggested two variants in the cat homolog for Hairless (HR) (HR lysine demethylase and nuclear receptor corepressor) as candidate causal gene variants. The lykoi cat was a compound heterozygote for two loss of function variants in HR, an exon 3 c.1255_1256dupGT (chrB1:36040783), which should produce a stop codon at amino acid 420 (p.Gln420Serfs*100) and, an exon 18 c.3389insGACA (chrB1:36051555), which should produce a stop codon at amino acid position 1130 (p.Ser1130Argfs*29). Ascertainment of 14 additional cats from founder lineages from Canada, France and different areas of the USA identified four additional loss of function HR variants likely causing the highly similar phenotypic hair coat across the diverse cats. The novel variants in HR for cat hypotrichia can now be established between minor differences in the phenotypic presentations.Peer reviewe

The Demographics of Canine Hip Dysplasia in the United States and Canada

Canine hip dysplasia (CHD) is a common problem in veterinary medicine. We report the demographics of CHD using the entire hip dysplasia registry from the Orthopedic Foundation for Animals, analyzing differences by breed, sex, laterality, seasonal variation in birth, and latitude. There were 921,046 unique records. Each dog was classified using the American Kennel Club (AKC) and Fédération Cynologique Internationale (FCI) systems. Statistical analysis was performed with bivariate and logistic regression procedures. The overall CHD prevalence was 15.56%. The OR for CHD was higher in females (1.05), those born in spring (1.14) and winter (1.13), and those in more southern latitudes (OR 2.12). Within AKC groups, working dogs had the highest risk of CHD (OR 1.882) with hounds being the reference group. Within FCI groups, the pinscher/molossoid group had the highest risk of CHD (OR 4.168) with sighthounds being the reference group. The similarities between CHD and DDH are striking. Within DDH there are two different types, the typical infantile DDH and the late onset adolescent/adult acetabular dysplasia, with different demographics; the demographics of CHD are more similar to the later onset DDH group. Comparative studies of both disorders should lead to a better understanding of both CHD and DDH