Publications by authors named "Leslie A Lyons"

100 Publications

Patterns of allele frequency differences among domestic cat breeds assessed by a 63K SNP array.

PLoS One 2021 25;16(2):e0247092. Epub 2021 Feb 25.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.

Cats are ubiquitous companion animals that have been keenly associated with humans for thousands of years and only recently have been intentionally bred for aesthetically appealing coat looks and body forms. The intense selection on single gene phenotypes and the various breeding histories of cat breeds have left different marks on the genomes. Using a previously published 63K Feline SNP array dataset of twenty-six cat breeds, this study utilized a genetic differentiation-based method (di) to empirically identify candidate regions under selection. Defined as three or more overlapping (500Kb) windows of high levels of population differentiation, we identified a total of 205 candidate regions under selection across cat breeds with an average of 6 candidate regions per breed and an average size of 1.5 Mb per candidate region. Using the combined size of candidate regions of each breed, we conservatively estimate that a minimum of ~ 0.1-0.7% of the autosomal genome is potentially under selection in cats. As positive controls and tests of our methodology, we explored the candidate regions of known breed-defining genes (e.g., FGF5 for longhaired breeds) and we were able to detect the genes within candidate regions, each in its corresponding breed. For breed specific exploration of candidate regions under selection, eleven representative candidate regions were found to encompass potential candidate genes for several phenotypes such as brachycephaly of Persian (DLX6, DLX5, DLX2), curled ears of American Curl (MCRIP2, PBX1), and body-form of Siamese and Oriental (ADGRD1), which encourages further molecular investigations. The current assessment of the candidate regions under selection is empiric and detailed analyses are needed to rigorously disentangle effects of demography and population structure from artificial selection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247092PLOS
February 2021

Author Correction: Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus).

Sci Rep 2021 Feb 17;11(1):4375. Epub 2021 Feb 17.

Faculty of Science, Sydney School of Veterinary Science, University of Sydney, Sydney, NSW, Australia.

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http://dx.doi.org/10.1038/s41598-021-83769-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889845PMC
February 2021

Ultracontinuous single haplotype genome assemblies for the domestic cat (Felis catus) and Asian leopard cat (Prionailurus bengalensis).

J Hered 2020 Dec 11. Epub 2020 Dec 11.

Veterinary Integrative Biosciences, Texas A&M University, College Station, TX.

In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase >99.9% of the reads into the two species' haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in one or two large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation and speciation.
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http://dx.doi.org/10.1093/jhered/esaa057DOI Listing
December 2020

Exploratory study of cat adoption in families of children with autism: Impact on children's social skills and anxiety.

J Pediatr Nurs 2020 Dec 5;58:28-35. Epub 2020 Dec 5.

Department of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri, 1600 E. Rollins St., Columbia, MO 65211, USA.

Purpose: The diagnosis of Autism Spectrum Disorder (ASD) occurs in one in 54 children and companion animals (CA) are common in families of children with ASD. Despite evidence of CA ownership benefits for children with ASD, little is known about cats. The purpose was to explore the impact of shelter cat adoption by families of children with ASD.

Design And Methods: This was the first randomized controlled trial of adoption of a temperament screened cat by families of children with ASD. Families assigned to the treatment group adopted a cat and were followed for 18 weeks. Families assigned to the control group were followed for 18 weeks without intervention, then converted to treatment, by adopting a cat and were followed another 18 weeks. Adopted cats were screened using the Feline Temperament Profile to identify a calm temperament. Surveys measured children's social skills and anxiety and parent/child cat bonding.

Results: Our study (N = 11) found cat adoption was associated with greater Empathy and less Separation Anxiety for children with ASD, along with fewer problem behaviors including Externalizing, Bullying and Hyperactivity/Inattention. Parents and children reported strong bonds to the cats.

Conclusion: This exploratory study found introduction of a cat into the home may have a positive impact on children with ASD and their parents. Based on this intial finding, future studies with larger sample sizes are recommended.

Practice Implications: If parents of children with ASD are considering cat adoption, health care providers might consider recommending adoption of a cat screened for calm temperament.
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http://dx.doi.org/10.1016/j.pedn.2020.11.011DOI Listing
December 2020

Precision medicine in cats-The right biomedical model may not be the mouse!

Authors:
Leslie A Lyons

PLoS Genet 2020 12 8;16(12):e1009177. Epub 2020 Dec 8.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States of America.

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http://dx.doi.org/10.1371/journal.pgen.1009177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723241PMC
December 2020

Genetic relationships and inbreeding levels among geographically distant populations of Felis catus from Japan and the United States.

Genomics 2021 Jan 25;113(1 Pt 1):104-110. Epub 2020 Nov 25.

Research and Development Section, Anicom Specialty Medical Institute Inc., Kanagawa, Japan.

Pedigreed cats have traditionally been mated with close relatives, which increases the risks for inbreeding depression and genetic disorders. We evaluated the genome-wide population structure and the degree of inbreeding of 1022 cats, including 13 pedigreed and two random bred populations from Japan and the USA, using single nucleotide polymorphism array-based data. Ancestry structure analysis revealed Japan's American Curl, Norwegian Forest, and Siamese cat populations were genetically distinct from their American counterparts. Furthermore, we found an ancestral genetic component shared between five pedigreed and random bred Japanese cats, suggesting the breeds were admixed with Japanese cats or cats of east Asian origin. Between-country differences in inbreeding estimates based on runs of homozygosity were found for Maine Coon, Siamese, and random bred cats. To reduce the risks of inbreeding depression and genetic disorders, particularly for highly inbred breeds, such as Abyssinian cats, as well as Russian Blue and Siamese cats in the USA, appropriate breeding practices must be observed, including mating practices that increase the genetic diversity.
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http://dx.doi.org/10.1016/j.ygeno.2020.11.018DOI Listing
January 2021

Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus).

Sci Rep 2020 11 5;10(1):19194. Epub 2020 Nov 5.

Faculty of Science, Sydney School of Veterinary Science, University of Sydney, Sydney, NSW, Australia.

Diabetes mellitus, a common endocrinopathy affecting domestic cats, shares many clinical and pathologic features with type 2 diabetes in humans. In Australia and Europe, diabetes mellitus is almost four times more common among Burmese cats than in other breeds. As a genetically isolated population, the diabetic Australian Burmese cat provides a spontaneous genetic model for studying diabetes mellitus in humans. Studying complex diseases in pedigreed breeds facilitates tighter control of confounding factors including population stratification, allelic frequencies and environmental heterogeneity. We used the feline SNV array and whole genome sequence data to undertake a genome wide-association study and runs of homozygosity analysis, of a case-control cohort of Australian and European Burmese cats. Our results identified diabetes-associated haplotypes across chromosomes A3, B1 and E1 and selective sweeps across the Burmese breed on chromosomes B1, B3, D1 and D4. The locus on chromosome B1, common to both analyses, revealed coding and splice region variants in candidate genes, ANK1, EPHX2 and LOX2, implicated in diabetes mellitus and lipid dysregulation. Mapping this condition in Burmese cats has revealed a polygenic spectrum, implicating loci linked to pancreatic beta cell dysfunction, lipid dysregulation and insulin resistance in the pathogenesis of diabetes mellitus in the Burmese cat.
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http://dx.doi.org/10.1038/s41598-020-76166-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644637PMC
November 2020

A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism.

PLoS Genet 2020 10 22;16(10):e1008926. Epub 2020 Oct 22.

Division of Animal Sciences, School of Medicine, University of Missouri, Columbia, Missouri, United States of America.

The domestic cat (Felis catus) numbers over 94 million in the USA alone, occupies households as a companion animal, and, like humans, suffers from cancer and common and rare diseases. However, genome-wide sequence variant information is limited for this species. To empower trait analyses, a new cat genome reference assembly was developed from PacBio long sequence reads that significantly improve sequence representation and assembly contiguity. The whole genome sequences of 54 domestic cats were aligned to the reference to identify single nucleotide variants (SNVs) and structural variants (SVs). Across all cats, 16 SNVs predicted to have deleterious impacts and in a singleton state were identified as high priority candidates for causative mutations. One candidate was a stop gain in the tumor suppressor FBXW7. The SNV is found in cats segregating for feline mediastinal lymphoma and is a candidate for inherited cancer susceptibility. SV analysis revealed a complex deletion coupled with a nearby potential duplication event that was shared privately across three unrelated cats with dwarfism and is found within a known dwarfism associated region on cat chromosome B1. This SV interrupted UDP-glucose 6-dehydrogenase (UGDH), a gene involved in the biosynthesis of glycosaminoglycans. Importantly, UGDH has not yet been associated with human dwarfism and should be screened in undiagnosed patients. The new high-quality cat genome reference and the compilation of sequence variation demonstrate the importance of these resources when searching for disease causative alleles in the domestic cat and for identification of feline biomedical models.
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http://dx.doi.org/10.1371/journal.pgen.1008926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581003PMC
October 2020

Direct-to-Consumer Genetic Testing for Domestic Cats.

Vet Clin North Am Small Anim Pract 2020 Sep 11;50(5):991-1000. Epub 2020 Jul 11.

Department of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri - Columbia, E109 Vet Med Building, 825 East Campus Loop, Columbia, MO 65211, USA.

The era of precision/genomic medicine has arrived, including its application within veterinary medicine for the health care of companion animals. The plummeting costs of assaying large groups of genetic tests into one panel has led many laboratories offering direct-to-consumer (DTC) genetic testing for animals, including cats. However, proper education of the consumer and the veterinarian is lacking, causing a significant lack of genetic counseling pertaining to the results of the genetic tests. This article addresses the current state of DTC testing in domestic cats and the implications for veterinary care.
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http://dx.doi.org/10.1016/j.cvsm.2020.05.004DOI Listing
September 2020

Precision/Genomic Medicine for Domestic Cats.

Vet Clin North Am Small Anim Pract 2020 Sep 8;50(5):983-990. Epub 2020 Jul 8.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, E109 Vet Med Building, 825 East Campus Loop, Columbia, MO 65211, USA. Electronic address:

The era of Precision / Genomic Medicine has arrived and can improve the veterinary healthcare of companion animals. The goal of Precision / Genomic Medicine is to use an individual's DNA signature / profile to tailor their treatments of their specific health problems. Whole genome sequencing is now a cost-effective diagnostic tool, leading to the discovery of DNA variants associated with health outcomes. These DNA variants become genetic tests and can readily be applied to future cases of individuals with similar symptoms. This article addresses the current state of Precision Medicine in domestic cats and the implications for veterinary care.
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http://dx.doi.org/10.1016/j.cvsm.2020.05.005DOI Listing
September 2020

Werewolf, There Wolf: Variants in Associated with Hypotrichia and Roaning in the Lykoi Cat Breed.

Genes (Basel) 2020 06 22;11(6). Epub 2020 Jun 22.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.

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 ) 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.
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http://dx.doi.org/10.3390/genes11060682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348984PMC
June 2020

A Deletion in is Associated with a Heritable Forebrain Commissural Malformation Concurrent with Ventriculomegaly and Interhemispheric Cysts in Cats.

Genes (Basel) 2020 06 19;11(6). Epub 2020 Jun 19.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.

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 () (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, mRNA is expressed within the roof plate when commissural axons initiate ventrally-directed growth. This finding emphasized the importance of in the neurodevelopmental process in the mammalian brain. A genetic test can be developed for use by cat breeders to eradicate this variant.
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http://dx.doi.org/10.3390/genes11060672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349246PMC
June 2020

Neuronal Ceroid Lipofuscinosis in a Domestic Cat Associated with a DNA Sequence Variant That Creates a Premature Stop Codon in .

G3 (Bethesda) 2020 08 5;10(8):2741-2751. Epub 2020 Aug 5.

Department of Veterinary Medicine and Surgery.

A neutered male domestic medium-haired cat presented at a veterinary neurology clinic at 20 months of age due to progressive neurological signs that included visual impairment, focal myoclonus, and frequent severe generalized seizures that were refractory to treatment with phenobarbital. Magnetic resonance imaging revealed diffuse global brain atrophy. Due to the severity and frequency of its seizures, the cat was euthanized at 22 months of age. Microscopic examination of the cerebellum, cerebral cortex and brainstem revealed pronounced intracellular accumulations of autofluorescent storage material and inflammation in all 3 brain regions. Ultrastructural examination of the storage material indicated that it consisted almost completely of tightly-packed membrane-like material. The clinical signs and neuropathology strongly suggested that the cat suffered from a form of neuronal ceroid lipofuscinosis (NCL). Whole exome sequence analysis was performed on genomic DNA from the affected cat. Comparison of the sequence data to whole exome sequence data from 39 unaffected cats and whole genome sequence data from an additional 195 unaffected cats revealed a homozygous variant in that was unique to the affected cat. This variant was predicted to cause a stop gain in the transcript due to a guanine to adenine transition (ENSFCAT00000025909:c.668G > A; XM_003987007.5:c.668G > A) and was the sole loss of function variant detected. variants in other species, including humans, dogs, and sheep, are associated with the CLN6 form of NCL. Based on the affected cat's clinical signs, neuropathology and molecular genetic analysis, we conclude that the cat's disorder resulted from the loss of function of CLN6. This study is only the second to identify the molecular genetic basis of a feline NCL. Other cats exhibiting similar signs can now be screened for the variant. This could lead to establishment of a feline model of CLN6 disease that could be used in therapeutic intervention studies.
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http://dx.doi.org/10.1534/g3.120.401407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407459PMC
August 2020

Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy.

Am J Hum Genet 2020 06 7;106(6):893-904. Epub 2020 May 7.

CHU Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes Cedex 1, France; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France. Electronic address:

Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous KIF3B variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G>C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by KIF3B. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T>C (p.Leu523Pro) KIF3B variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length in vitro in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of KIF3B mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive KIF3B models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G>A (p.Ala334Thr) KIF3B variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and in vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.
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http://dx.doi.org/10.1016/j.ajhg.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273529PMC
June 2020

Applying genomic data in wildlife monitoring: Development guidelines for genotyping degraded samples with reduced single nucleotide polymorphism panels.

Mol Ecol Resour 2020 May 30;20(3). Epub 2020 Jan 30.

Conservation Genetics Group, Senckenberg Research Institute and Natural History Museum Frankfurt, Gelnhausen, Germany.

The genomic era has led to an unprecedented increase in the availability of genome-wide data for a broad range of taxa. Wildlife management strives to make use of these vast resources to enable refined genetic assessments that enhance biodiversity conservation. However, as new genomic platforms emerge, problems remain in adapting the usually complex approaches for genotyping of noninvasively collected wildlife samples. Here, we provide practical guidelines for the standardized development of reduced single nucleotide polymorphism (SNP) panels applicable for microfluidic genotyping of degraded DNA samples, such as faeces or hairs. We demonstrate how microfluidic SNP panels can be optimized to efficiently monitor European wildcat (Felis silvestris S.) populations. We show how panels can be set up in a modular fashion to accommodate informative markers for relevant population genetics questions, such as individual identification, hybridization assessment and the detection of population structure. We discuss various aspects regarding the implementation of reduced SNP panels and provide a framework that will allow both molecular ecologists and practitioners to help bridge the gap between genomics and applied wildlife conservation.
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http://dx.doi.org/10.1111/1755-0998.13136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199164PMC
May 2020

Clinical, metabolic, and genetic characterization of hereditary methemoglobinemia caused by cytochrome b reductase deficiency in cats.

J Vet Intern Med 2019 Nov 25;33(6):2725-2731. Epub 2019 Oct 25.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri.

Two non-pedigreed male castrated cats had persistent cyanosis over a 3-year observation period. Clinical cardiopulmonary evaluations did not reveal abnormalities, but the blood remained dark after exposure to air. Erythrocytic methemoglobin concentrations were high (~40% of hemoglobin) and cytochrome b reductase (CYB5R) activities in erythrocytes were low (≤15% of control). One cat remained intolerant of exertion, and the other cat developed anemia and died due to an unidentified comorbidity. Whole-genome sequencing revealed a homozygous c.625G>A missense variant (B4:137967506) and a c.232-1G>C splice acceptor variant (B4:137970815) in CYB5R3, respectively, which were absent in 193 unaffected additional cats. The p.Gly209Ser missense variant likely disrupts a nicotinamide adenine dinucleotide (NADH)-binding domain, while the splicing error occurs at the acceptor site for exon 4, which likely affects downstream translation of the protein. The 2 novel CYB5R3 variants were associated with methemoglobinemia using clinical, biochemical, genomics, and in silico protein studies. The variant prevalence is unknown in the cat population.
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http://dx.doi.org/10.1111/jvim.15637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872605PMC
November 2019

Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease.

Cell Metab 2019 12 17;30(6):1007-1023.e5. Epub 2019 Oct 17.

Molecular, Cellular, and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA. Electronic address:

Mild reduction in food intake was recently shown to slow polycystic kidney disease (PKD) progression in mouse models, but whether the effect was due to solely reduced calories or some other aspect of the diet has been unclear. We now show that the benefit is due to the induction of ketosis. Time-restricted feeding, without caloric reduction, strongly inhibits mTOR signaling, proliferation, and fibrosis in the affected kidneys in a PKD rat model. A ketogenic diet had a similar effect and led to regression of renal cystic burden. Acute fasting in rat, mouse, and feline models of PKD results in rapid reduction of cyst volume, while oral administration of the ketone β-hydroxybutyrate (BHB) in rats strongly inhibits PKD progression. These results suggest that cystic cells in PKD are metabolically inflexible, which could be exploited by dietary interventions or supplementation with BHB, representing a new therapeutic avenue to treat PKD.
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http://dx.doi.org/10.1016/j.cmet.2019.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904245PMC
December 2019

Genomic approaches to identify hybrids and estimate admixture times in European wildcat populations.

Sci Rep 2019 08 12;9(1):11612. Epub 2019 Aug 12.

Area per la Genetica della Conservazione (BIO-CGE), Istituto Superiore per la Protezione e la Ricerca Ambientale (ISPRA), Ozzano dell'Emilia, Italy.

The survival of indigenous European wildcat (Felis silvestris silvestris) populations can be locally threatened by introgressive hybridization with free-ranging domestic cats. Identifying pure wildcats and investigating the ancestry of admixed individuals becomes thus a conservation priority. We analyzed 63k cat Single Nucleotide Polymorphisms (SNPs) with multivariate, Bayesian and gene-search tools to better evaluate admixture levels between domestic and wild cats collected in Europe, timing and ancestry proportions of their hybrids and backcrosses, and track the origin (wild or domestic) of the genomic blocks carried by admixed cats, also looking for possible deviations from neutrality in their inheritance patterns. Small domestic ancestry blocks were detected in the genomes of most admixed cats, which likely originated from hybridization events occurring from 6 to 22 generations in the past. We identified about 1,900 outlier coding genes with excess of wild or domestic ancestry compared to random expectations in the admixed individuals. More than 600 outlier genes were significantly enriched for Gene Ontology (GO) categories mainly related to social behavior, functional and metabolic adaptive processes (wild-like genes), involved in cognition and neural crest development (domestic-like genes), or associated with immune system functions and lipid metabolism (parental-like genes). These kinds of genomic ancestry analyses could be reliably applied to unravel the admixture dynamics in European wildcats, as well as in other hybridizing populations, in order to design more efficient conservation plans.
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http://dx.doi.org/10.1038/s41598-019-48002-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691104PMC
August 2019

Kidney and cystic volume imaging for disease presentation and progression in the cat autosomal dominant polycystic kidney disease large animal model.

BMC Nephrol 2019 07 12;20(1):259. Epub 2019 Jul 12.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Background: Approximately 30% of Persian cats have a c.10063C > A variant in polycystin 1 (PKD1) homolog causing autosomal dominant polycystic kidney disease (ADPKD). The variant is lethal in utero when in the homozygous state and is the only ADPKD variant known in cats. Affected cats have a wide range of progression and disease severity. However, cats are an overlooked biomedical model and have not been used to test therapeutics and diets that may support human clinical trials. To reinvigorate the cat as a large animal model for ADPKD, the efficacy of imaging modalities was evaluated and estimates of kidney and fractional cystic volumes (FCV) determined.

Methods: Three imaging modalities, ultrasonography, computed tomography (CT), and magnetic resonance imaging examined variation in disease presentation and disease progression in 11 felines with ADPKD. Imaging data was compared to well-known biomarkers for chronic kidney disease and glomerular filtration rate. Total kidney volume, total cystic volume, and FCV were determined for the first time in ADPKD cats. Two cats had follow-up examinations to evaluate progression.

Results: FCV measurements were feasible in cats. CT was a rapid and an efficient modality for evaluating therapeutic effects that cause alterations in kidney volume and/or FCV. Biomarkers, including glomerular filtration rate and creatinine, were not predictive for disease progression in feline ADPKD. The wide variation in cystic presentation suggested genetic modifiers likely influence disease progression in cats. All imaging modalities had comparable resolutions to those acquired for humans, and software used for kidney and cystic volume estimates in humans proved useful for cats.

Conclusions: Routine imaging protocols used in veterinary medicine are as robust and efficient for evaluating ADPKD in cats as those used in human medicine. Cats can be identified as fast and slow progressors, thus, could assist with genetic modifier discovery. Software to measure kidney and cystic volume in human ADPKD kidney studies is applicable and efficient in cats. The longer life and larger kidney size span than rodents, similar genetics, disease presentation and progression as humans suggest cats are an efficient biomedical model for evaluation of ADPKD therapeutics.
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http://dx.doi.org/10.1186/s12882-019-1448-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625046PMC
July 2019

Author Correction: Applications and efficiencies of the first cat 63 K DNA array.

Sci Rep 2019 Mar 12;9(1):4664. Epub 2019 Mar 12.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, Columbia, MO, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-38073-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411770PMC
March 2019

Compatibility of Cats With Children in the Family.

Front Vet Sci 2018 19;5:278. Epub 2018 Nov 19.

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.

Although studies involving pet dogs and cats, and human adults and children, have been reported, the specific interactions between cats and children have not. This study sought information from parents about the cat's role in families that have at least one child 3-12 years of age and at least one cat. Demographic data on cat source, breed, gender/neuter status, was sought as well as information on adults and children in the families and on affectionate, aggressive, fearful, and playful responses of the cats to children. A convenience sample was recruited via listservs for pet owners and parents. Using a pilot tested web survey, descriptive statistics were based on 865 respondents. Multi-variate statistical analyses were conducted on data from 665 respondents with complete responses for all items, including respondents' locations and whether cats were adopted as kittens. Multi-variate analyses included consideration of demographic data, geographic region of respondents, behavioral characteristics of the cats, and responses of the children to the cats. From descriptive statistics, cats' affection was more typical with adults than young children. Neuter status or gender was unrelated to cats' aggression or affection. Being the family's only cat was associated with heightened aggression and reduced affection. Younger cats were more likely to be affectionate. Multivariate analysis revealed three primary factors accounting for children's compatibility with the specified cat: positive interactions of the cat, aggression/fearfulness of cat, and the cat's playfulness and children's reaction to the cats. Positive child-cat relationships were more typical with two or more adults and multiple cats in the home. Old cats were the least satisfactory. A breeder or shelter was a better source than as a feral, from a newspaper ad, or another source. European respondents rated their cats' interactions with children more favorably than in U.S./Canada. This difference may reflect the European adoptions more frequently being of kittens, often purebred, assuring more early handling within the family. A noteworthy finding was that all family participants, humans, and pets alike, affect the cat-child relationship, and these results reveal that many variables can play a role in achieving a desirable relationship for a cat and child.
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http://dx.doi.org/10.3389/fvets.2018.00278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252378PMC
November 2018

Identification and quantification of domestic feline cytochrome P450 transcriptome across multiple tissues.

J Vet Pharmacol Ther 2019 Jan 31;42(1):7-15. Epub 2018 Aug 31.

Lab Sciences, VMRD, Zoetis, Kalamazoo, Michigan.

Understanding of cytochrome P450 (CYP) isoform distribution and function in the domestic feline is limited. Only a few studies have defined individual CYP isoforms across metabolically relevant tissues, hampering the ability to predict drug metabolism and potential drug-drug interactions. Using RNA sequencing (RNA-seq), transcriptomes from the 99 Lives Cat Genome Sequencing Initiative databank combined with experimentally acquired whole transcriptome sequencing of healthy, adult male (n = 2) and female (n = 2) domestic felines, expression of 42 CYP isoforms were identified in 20 different tissues. Thirty-seven of these isoforms had not been previously reported in cats. Depending on the tissue, three to twenty-nine CYP isoform transcripts were expressed. The feline genome annotations did not differentiate CYP2E1 and 2E2 genes, demonstrating poor annotation for this gene using the reference genome. As the majority of the sequences are based on automated pipelines, complete cDNA sequences for translation into CYP protein sequences could not be determined. This study is the first to identify and characterize 37 additional CYP isoforms in feline tissues, increasing the number of identified CYP from the previously reported seven isoforms to 42 across 20 tissues.
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http://dx.doi.org/10.1111/jvp.12708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322962PMC
January 2019

Author Correction: Applications and efficiencies of the first cat 63K DNA array.

Sci Rep 2018 Jun 4;8(1):8746. Epub 2018 Jun 4.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, Columbia, MO, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-26885-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986783PMC
June 2018

Applications and efficiencies of the first cat 63K DNA array.

Sci Rep 2018 05 4;8(1):7024. Epub 2018 May 4.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, Columbia, MO, USA.

The development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array's genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50-1,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations.
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http://dx.doi.org/10.1038/s41598-018-25438-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935720PMC
May 2018

Affectionate Interactions of Cats with Children Having Autism Spectrum Disorder.

Front Vet Sci 2018 12;5:39. Epub 2018 Mar 12.

Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.

Mental and physical benefits of dogs have been reported for adults and children with special needs, but less is known about benefits of cats for children. A cat that can be held by a child could provide important therapeutic companionship for children with severe or less severe autism spectrum disorder (ASD) who otherwise may lack prosocial behaviors. Because relatively little is known about the behavior of cats around children, we conducted this study. Phase 1 gathered web-survey data from families having an adult cat and a child with ASD ( = 64). In Phase 2, there were direct telephone interviews of parents having a child with severe ASD ( = 16) or less severe ASD ( = 11), or typical development ( = 17). From the Phase 1 web survey of families with ASD children (full range of severities), affectionate interactions of the cats with children were common. Most parents with ASD children volunteered positive comments regarding the cat, such as calming the child, being a soothing protector or a guardian. In the interviews in Phase 2, for all three groups, most parents characterized cats as at least moderately affectionate toward the child. However, cats living with severe ASD children were reported to exhibit less affection than those living with typically developing children or children with less severe ASD. A minority of cats in each group showed some aggression to the specified child; this was not elevated with ASD children. Responses suggested that the cats adopted as kittens were more affectionate and less aggressive to all categories of children than those adopted as adults. Overall, participants reported that ASD children's behaviors indicated that they valued the relationship with the cat, similar to typically developing children, pointing to the importance and potential usefulness of selecting affectionate and compatible cats for ASD children.
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http://dx.doi.org/10.3389/fvets.2018.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862067PMC
March 2018

An unresponsive progressive pustular and crusting dermatitis with acantholysis in nine cats.

Vet Dermatol 2018 Feb 6;29(1):81-e33. Epub 2017 Oct 6.

Department of Veterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA, 95616, USA.

Background: Between 2000 and 2012, nine cats were examined with a visually distinctive, progressive crusting dermatitis that was poorly responsive to all attempted therapies.

Objectives: Documentation of clinical and histopathological findings of this disease.

Animals: Nine privately owned cats.

Methods: Retrospective study.

Results: Eight neutered males and one (presumably spayed) female ranging in age from two to eight years, presented for a progressive, well-demarcated, crusting dermatitis with variable pruritus of 1.5 months to five years duration. All cats lived in northern California, USA; seven lived within a 30 mile radius. Two males were littermates. Histopathological investigation showed both parakeratotic and orthokeratotic crusts, intraepidermal pustules and superficial folliculitis with rare to frequent acantholytic cells. Bacterial and fungal cultures were performed in six cats: meticillin-susceptible Staphylococcus pseudintermedius was isolated in three cats, two colonies of Trichophyton terrestre and three of Malassezia pachydermatis were isolated from one cat each. Treatment with various antibiotics, antifungal and a variety of immunosuppressive medications did not alter the progressive nature of the skin disease.

Conclusions And Clinical Importance: The described disease shares some clinical and histopathological features with pemphigus foliaceus, but the lack of response to treatment, its progressive nature and the possible relatedness of some of the cats set it apart. The aetiology of this acantholytic dermatitis remains unknown.
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http://dx.doi.org/10.1111/vde.12501DOI Listing
February 2018

Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes).

Sci Rep 2017 03 21;7:43918. Epub 2017 Mar 21.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.

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.
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http://dx.doi.org/10.1038/srep43918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359545PMC
March 2017

Erratum to: A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats.

Mamm Genome 2017 04;28(3-4):152-154

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri - Columbia, Columbia, MO, 65211, USA.

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http://dx.doi.org/10.1007/s00335-016-9676-1DOI Listing
April 2017