Leslie A. Lyons

• Doctor of Philosophy
• Professor - Endowed at University of Missouri

Background: Atherosclerosis, a chronic inflammatory vascular disease driven by the accumulation of LDL-derived cholesterol on arterial walls, is the leading cause of mortality worldwide but is rare in animals. We recently identified spontaneous atherosclerosis in the Korat cat breed, characterized by severe hypercholesterolemia and clinical signs o...

Assessing the pathogenicity of a disease-associated genetic variant in animals accurately is vital, both on a population and individual scale. At the population level, breeding decisions based on invalid DNA tests can lead to the incorrect inclusion or exclusion of animals and compromise the long-term health of a population, and at the level of the...

Assessing the pathogenicity of a disease-associated variant in animals accurately is vital, both on a population and individual scale. At the population level, breeding decisions based on invalid DNA tests can lead to the incorrect exclusion of animals and compromise the long-term health of a population, and at the level of the individual animal, l...

Simple Summary Aesthetic traits are major components of modern feline breeds. Each breed is defined by a standard specifying morphology; coat length, texture, and colour; and eye colour. Considering the coat and eye colour may help breeders in managing their breeding stocks to optimise their mating, but it also has an impact on the health and well-...

This study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from two different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some...

Case summary This report describes the diagnostic findings, natural history and genetic analysis of the candidate gene Forkhead Box F1 ( FOXF1) in a young cat with developmental lung disease and high probability of pulmonary hypertension. A 1-year-old male entire Chartreux cat was referred for cardiac murmur investigation and exercise intolerance....

Cats with a distinctive white hair pattern of unknown molecular cause have been discovered in the Finnish domestic cat population. Based on the unique appearance of these cats, we have named this phenotype salmiak (“salty licorice”). The use of a commercially available panel test to genotype four salmiak‐colored cats revealed the absence of all kno...

The Pallas’s cat (Otocolobus manul) is one of the most understudied taxa in the Felidae family. The species is currently assessed as being of “Least Concern” in the IUCN Red List, but this assessment is based on incomplete data. Additional ecological and genetic information is necessary for the long-term in situ and ex situ conservation of this spe...

The fishing cat, Prionailurus viverrinus, faces a population decline, increasing the importance of maintaining healthy zoo populations. Unfortunately, zoo-managed individuals currently face a high prevalence of transitional cell carcinoma (TCC), a form of bladder cancer. To investigate the genetics of inherited diseases among captive fishing cats,...

A stray cat, an intact female Japanese domestic shorthair cat of unknown age (suspected to be a young adult), was rescued. The cat was lethargic and thin and had marked skin fragility, delayed wound healing without skin hyperextensibility, and hind limb proprioceptive ataxia and paresis. Survey radiography, computed tomography, and magnetic resonan...

X‐linked muscular dystrophy in cats (FXMD) is an uncommon disease, with few reports describing its pathogenic genetic variants. A 9‐year‐old castrated male domestic shorthair cat was presented with persistent muscle swelling and breathing difficulty from 3 years of age. Serum activity of alanine aminotransferase, aspartate transaminase, and creatin...

Introduction The correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for va...

Background Muscular dystrophies (MDs) are a large, heterogeneous group of degenerative muscle diseases. X‐linked dystrophin‐deficient MD in cats is the first genetically characterized cat model for a human disease and a few novel forms have been identified. Hypothesis/Objectives Muscular dystrophy was suspected in a young male domestic shorthair c...

The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discer...

Domestic cats were derived from the Near Eastern wildcat (Felis lybica), after which they dispersed with peolple into Europe. As they did so, it is possible that they interbred with the indigenous population of European wildcats (Felis silvestris). Gene flow between incoming domestic animals and closely related indigenous wild species has been prev...

Objectives The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats. Methods Clinical and genetic analyses were conducted on a Siamese cat family (n = 18), including two siblings with RH. Radiographs were obtained for the affected kittens and echocardiograms of an affected kitten an...

Background Ehlers‐Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders occurring in both human and veterinary patients. The genetics of these disorders are poorly described in small animal patients. Hypothesis/Objectives Define the clinical manifestations and genetic cause of a suspected form of EDS in a cat....

Objectives: A 14-week-old female domestic longhair kitten presented with shifting lameness and disproportionately smaller size compared with a co-housed littermate. Methods: Hematology and serum biochemical testing were conducted to investigate causes for delayed growth, and radiographs of the appendicular skeleton were obtained. Results: The...

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and communication. Autistic children suffer from social cognitive difficulties. There is no specific treatment for ASD, but ongoing individualized care can lead to an improvement in symptoms. Adopting a pet into a family with an autistic chi...

Case summary A 9-month-old entire male domestic longhair cat presented with a history of pathological fractures, chronic musculoskeletal pain and poor growth. Multiple facial and skeletal abnormalities were identified on physical examination and advanced imaging (CT and radiographs). A variant in CTSK was identified in the affected cat following wh...

The fishing cat, Prionailurus viverrinus, displays a fish hunting behavior uncommon among most other cats. Estimated population declines in the wild increase the significance of its existing zoo populations, particularly with a recent high prevalence of transitional cell carcinoma (TCC), a form of bladder cancer. We hypothesize that its small capti...

Cat domestication likely initiated as a symbiotic relationship between wildcats ( Felis silvestris subspecies) and the peoples of developing agrarian societies in the Fertile Crescent. As humans transitioned from hunter-gatherers to farmers ~12,000 years ago, bold wildcats likely capitalized on increased prey density (i.e., rodents). Humans benefit...

Multiple ocular coloboma (MOC) is a long-standing health issue in captive snow leopards (Panthera uncia). Eyelid coloboma/agenesis is thought to be the most common MOC phenotype, often requiring surgery to correct eyelid deformities and/or alleviate ocular discomfort. Congenital eyelid coloboma have been documented and persist intermittently in the...

Objective Describe the clinical course and diagnostic and genetic findings in a cat with X‐linked myotubular myopathy. Case Summary A 7‐month‐old male Maine coon was evaluated for progressively worsening gait abnormalities and generalized weakness. Neurolocalization was to the neuromuscular system. Genetic testing for spinal muscular atrophy (LIX1...

The mutation rate is a fundamental evolutionary parameter with direct and appreciable effects on the health and function of individuals. Here, we examine this important parameter in the domestic cat, a beloved companion animal as well as a valuable biomedical model. We estimate a mutation rate of 0.86 × 10−8 per bp per generation for the domestic c...

The current feline genotyping array of 63 k single nucleotide polymorphisms has proven its utility for mapping within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of r...

Hypertrophic cardiomyopathy (HCM) is a common and potentially fatal heart disease in many cat breeds. An intronic variant in TNNT2, c.95‐108G>A, was recently reported as the cause of HCM in the Maine Coon. The aim of this study was to determine this variant’s allele frequency in different populations and its possible association with HCM. Based on...

Pathogenic variants in retinol dehydrogenase 5 (RDH5) attenuate supply of 11-cis-retinal to photoreceptors leading to a range of clinical phenotypes including night blindness due to markedly slowed rod dark adaptation and in some patients, macular atrophy. Current animal models (such as Rdh5-/- mice) fail to recapitulate the functional or degenerat...

Background: Cats are a common companion animal (CA) in US households, and many live in families of children with autism spectrum disorder (ASD). The prevalence of ASD is one in 54, and many children have behavior challenges as well as their diagnostic communication disorders. Objective: Benefits of CAs for children with ASD have been identified, bu...

The current feline genotyping array of 63k single nucleotide polymorphisms has proven its utility within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred ca...

Feline genomic medicine can decode human variants of uncertain significance (VUSs). Telomere-to-telomere genome assemblies are feasible for all felid species, supporting genetic evolution and speciation studies. Their highly conserved genomic organization compared to humans suggests cats may also decipher the intergenic variation affecting the 3D c...

The domestic cat (Felis silvestris catus) is a valued companion animal throughout the world. Over 60 different cat breeds are accepted for competition by the cat fancy registries in different countries. Genetic markers, including short tandem repeats and SNPs, are available to evaluate and manage levels of inbreeding and genetic diversity, populati...

Objective The aim of this study was to characterize the radiographic alignment of thoracic and pelvic limbs and evaluate for intervertebral disc disease in cats with feline disproportionate dwarfism (FDD). Study Design Observational cross-sectional study. Radiographic joint orientation angles were measured in 10 thoracic and pelvic limbs from 5 FDD...

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. Des...

The amyloidoses constitute a group of diseases occurring in humans and animals that are characterized by abnormal deposits of aggregated proteins in organs, affecting their structure and function. In the Abyssinian cat breed, a familial form of renal amyloidosis has been described. In this study, multi-omics analyses were applied and integrated to...

The mutation rate is a fundamental evolutionary parameter with direct and appreciable effects on the health and function of individuals. Here, we examine this important parameter in the domestic cat, a beloved companion animal as well as a valuable biomedical model. We estimate a mutation rate of 0.86 × 10 ⁻⁸ per bp per generation for the domestic...

Over 94 million domestic cats are susceptible to cancers and other common and rare diseases. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants. Presented is a 35.7 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. Whole exome sequencing...

Tabby patterns of fur coats are defining characteristics in wild and domestic felids. Historically, three autosomal alleles at one locus (Tabby): Abyssinian (Ta; a.k.a. ticked), mackerel (Tm; a.k.a. striped) and blotched (tb; a.k.a. classic, blotched) were thought to control these patterns in domestic cats and their breeds. Currently, at least thre...

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. Usi...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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 referen...

This project was part of the Feline Friends Study, which matches shelter cats with families of children with Autism Spectrum Disorder (ASD) to study children’s social behaviour and cats’ stress. Cats were screened for calm temperament using the Feline Temperament Profile (FTP). The FTP consists of ten phases, with a list of ‘acceptable’ and ‘questi...

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...

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 spo...

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 PacBi...

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 d...

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 educa...

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, present...

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...

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 atro...

Over 94 million domestic cats are considered pets, who, as our companions, are also susceptible to cancers, common and rare diseases. Whole exome sequencing (WES) is a cost-effective strategy to study their putative disease-causing variants. Presented is ~35.8 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering...

Madagascar does not have native wild felid species; however, distinct populations of free-ranging “forest cats” of unknown species are known throughout the island, including at Ankarafantsika National Park, Bezà Mahafaly Special Reserve, Makira Natural Park and the Masoala peninsula. Malagasy “forest cats” are commonly considered invasive lemur pre...

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 i...

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, 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 significant red...

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...

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 comple...

Chediak-Higashi Syndrome (CHS) is a well-characterized, autosomal recessively inherited lysosomal disease caused by mutations in lysosomal trafficking regulator (LYST). The feline model for CHS was originally maintained for ~20 years. However, the colonies were disbanded and the CHS cat model was lost to the research community before the causative...

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 Pac...

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 b5 reductase (CYB5R) activities in erythrocytes...

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, strong...

Targeted GBS is a recent approach for obtaining an effective characterization for hundreds to thousands of markers. The high throughput of next‐generation sequencing technologies, moreover, allows sample multiplexing. The aims of this study were to (i) define a panel of single nucleotide polymorphisms (SNPs) in the cat, (ii) use GBS for profiling 1...

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 (SNP...

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,...

Despite the contribution of a few major genes for disproportionate dwarfism in humans, many dwarf patients are yet genetically undiagnosed. In domestic cats, disproportionate dwarfism has led to the development of a defined breed, the Munchkin or Minuet. This study examined the genetic aspects of feline dwarfism to consider cats as a new biomedical...

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.

A novel coloration named ‘mocha’ has been identified in the Burmese cat breed from Thailand. Tyrosinase (TYR) mutations are known to be associated with coat coloration in cats, such as the sable Burmese, the points of the Siamese and albino cats. Additionally, sable Burmese that produced mocha‐colored cats had unexpected genotypes for TYR. Therefor...

Background Copy Number Variations (CNVs) have becoming very significant variants, representing a major source of genomic variation. CNVs involvement in phenotypic expression and different diseases has been widely demonstrated in humans as well as in many domestic animals. However, genome wide investigation on these structural variations is still mi...

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/...

Sequence diversity of Tp53 gene was analyzed in dog tumors to have an insight of accumulated somatic mutations in 18 samples belongs to 7 different types of cancers. Nine different polymorphic sites were observed in exon 3, 4 and 5, while 32 polymorphic sites are observed in intron 3, 4 and 9. Most of these alterations are heterozygous, locus c.76...

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 L...

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.

Scientific Reports 7: Article number: 43918; published online: 21 March 2017; updated: 18 May 2018 The Acknowledgements section in this Article is incomplete. “Funding was provided by The University of Missouri, College of Veterinary Medicine Clinician Scientist Grant 2014 (JWP). Funding for the 99 Lives Cat Genome Sequencing Initiative has been pr...

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...