Leigh Anne Clark

Leigh Anne Clark
Clemson University | CU · Department of Genetics and Biochemistry

Ph.D.

About

54
Publications
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Publications

Publications (54)
Article
Full-text available
Congenital idiopathic megaesophagus (CIM) is a gastrointestinal (GI) motility disorder of dogs in which reduced peristaltic activity and dilation of the esophagus prevent the normal transport of food into the stomach. Affected puppies regurgitate meals and water, fail to thrive, and experience complications such as aspiration pneumonia that may nec...
Article
Significance Through the study of a dental anomaly we identified a locus strongly associated with body size in the Shetland Sheepdog. Within this locus are variants in two genes: a substitution in FtsJ RNA 2′-O-Methyltransferase 3 ( FTSJ3 ) and a splice donor insertion in Growth Hormone 1 ( GH1 ). We demonstrated that the GH1 variant causes an abno...
Article
Full-text available
Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog. Hypothesis/objective: Clinical...
Article
Full-text available
Startle disease, or hyperekplexia, is a glycinergic disorder characterized by hypertonia and apnea that is triggered by noise and/or touch. Mutations in five genes have been associated with startle disease in humans, dogs, cattle, and mice. We identified a novel recessive startle disease in a family of Spanish greyhounds. Whole genome resequencing...
Article
Full-text available
The lack of an annotated reference sequence for the canine Y chromosome has limited evolutionary studies, as well as our understanding of the role of Y-linked sequences in phenotypes with a sex bias. In genome-wide association studies (GWASs), we observed spurious associations with autosomal SNPs when sex was unbalanced in case-control cohorts and...
Article
Full-text available
Background The antisense insertion of a canine short interspersed element (SINEC_Cf) in the pigmentation gene PMEL (or SILV) causes a coat pattern phenotype in dogs termed merle. Merle is a semi-dominant trait characterized by patches of full pigmentation on a diluted background. The oligo(dT) tract of the Merle retrotransposon is long and uninterr...
Article
Full-text available
Background Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips. LGMD has been clinically described in several breeds of dogs, but the responsible mutations are unknown. The clinical presentation in dogs is characterized by marked...
Article
Full-text available
Juvenile dermatomyositis (JDM) is a chronic inflammatory myopathy and vasculopathy driven by genetic and environmental influences. Here, we investigated the genetic underpinnings of an analogous, spontaneous disease of dogs also termed dermatomyositis (DMS). As in JDM, we observed a significant association with a haplotype of the major histocompati...
Data
MAP3K7CL indel with conservation and RUNX3 binding motif. UCSC 100 Vertebrates track for human chr21:29,130,846–29,130,860 showing the G insertion and seven base pair deletion created by MAP3K7CL indel (Dog c.383_392ACTCCACAAA>GACT). Bases in gray differ from the dog reference sequence. The canine sequence is highlighted in yellow. The RUNX3 bindin...
Data
Chromosome 10 variants segregating with the lead SNPs in the affected dogs. (PDF)
Data
Chromosome 31 variants segregating with the lead SNPs in the affected Shetland sheepdog. (PDF)
Data
Frequency of PAN2 and MAP3K7CL genotypes. (PDF)
Data
Clinical presentation of dermatomyositis. Canine dermatomyositis is a vasculopathy that initially manifests as cutaneous lesions across the bony prominences of the face, tail tip, limbs, and feet, shown here. Some dogs develop alopecia and more extensive lesions over time, resulting in dermal scarring associated with erythema and mottled pigmentati...
Data
Collie selective sweeps on chromosome 12. ZH(p) values for all creeping windows containing 50 or more SNPs are plotted against chromosome position. Creeping windows are ≤1 Mb. (PDF)
Data
SNPs exceeding Bonferroni significance (5.08X10-7). (PDF)
Data
Primers and genotyping method for variants. (PDF)
Data
Manhattan and quantile-quantile plots of combined DMS GWAS (97 cases vs. 68 controls). The –log10P-values (y-axis) for 98,520 Illumina SNPs are plotted against chromosome position (x-axis). The threshold for Bonferroni significance is shown as a black horizontal line. The P-value and position (canFam3) of the lead SNPs are reported. The Q-Q plot is...
Data
Three-locus genotype disease probabilities by sex. Probability of disease (y-axis) for all combinations of PAN2 (x-axis) and MAP3K7CL genotypes are plotted in dogs (73 affected and 145 unaffected males; 59 affected and 245 unaffected females) (top) homozygous and (bottom) heterozygous for DLA- DRB1*002:01. (PDF)
Data
Median age of onset for combinations of PAN2 and MAP3K7CL genotypes. Median age of onset is plotted for genotypes consisting of 2 (AAbb, aaBB, AaBb), 3 (AABb, AaBB), and 4 (AABB) risk alleles at PAN2 and MAP3K7CL. CC and Cc genotypes were combined for analyses. Number of individuals is shown to right. (PDF)
Data
Three-locus genotypes for 229 individuals of 30 breeds. (PDF)
Article
Full-text available
Nemaline myopathy (NM) is a congenital muscle disorder associated with muscle weakness, hypotonia, and rod bodies in the skeletal muscle fibers. Mutations in 10 genes have been implicated in human NM, but spontaneous cases in dogs have not been genetically characterized. We identified a novel recessive myopathy in a family of line-bred American bul...
Article
Congenital myasthenic syndromes (CMSs) are a group of rare genetic disorders of the neuromuscular junction resulting in structural or functional causes of fatigable weakness that usually begins early in life. Mutations in pre-synaptic, synaptic and post-synaptic proteins have been demonstrated in human cases, with more than half involving aberratio...
Article
Exocrine pancreatic insufficiency (EPI) is a digestive disorder resulting from the insufficient secretion of enzymes from the pancreas. In dogs, this condition is often attributed to pancreatic acinar atrophy, wherein the enzyme-producing acinar cells are believed to be destroyed through an autoimmune process. Although EPI affects many diverse bree...
Article
Full-text available
Congenital myasthenic syndromes (CMSs) are heterogeneous neuromuscular disorders characterized by skeletal muscle weakness caused by disruption of signal transmission across the neuromuscular junction (NMJ). CMSs are rarely encountered in veterinary medicine, and causative mutations have only been identified in Old Danish Pointing Dogs and Brahman...
Article
Exocrine pancreatic insufficiency (EPI) is a disease wherein pancreatic acinar cells fail to synthesize and secrete sufficient amounts of digestive enzymes for normal digestion of food. EPI affects many dog breeds, with a dramatically higher prevalence in the German shepherd dog (GSD) population. In this breed and perhaps others, EPI most often res...
Article
Exocrine pancreatic insufficiency (EPI) is a disorder wherein the pancreas fails to secrete adequate amounts of digestive enzymes. In dogs, EPI is usually the consequence of an autoimmune disease known as pancreatic acinar atrophy. Originally believed to be a simple autosomal recessive disorder, a test-breeding recently revealed that EPI has a more...
Article
Full-text available
Araucana chickens are known for their rounded, tailless rumps and tufted ears. Inheritance studies have shown that the rumpless (Rp) and ear-tufted (Et) loci each act in an autosomal dominant fashion, segregate independently, and are associated with an increased rate of embryonic mortality. To find genomic regions associated with Rp and Et, we gene...
Article
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The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (...
Article
Full-text available
Episodic falling syndrome (EFS) is a canine paroxysmal hypertonicity disorder found in Cavalier King Charles spaniels. Episodes are triggered by exercise, stress or excitement and characterized by progressive hypertonicity throughout the thoracic and pelvic limbs, resulting in a characteristic 'deer-stalking' position and/or collapse. We used a gen...
Article
Harlequin is a pigmentary trait of the domestic dog that is controlled by two autosomal loci: the melanosomal gene, SILV, and a modifier gene, harlequin (H), previously localized to chromosome 9. Heterozygosity for a retrotransposon insertion in SILV and a mutation in H causes a pattern of black patches on a white background. Homozygosity for H is...
Article
Full-text available
Naturally occurring cystic fibrosis (CF)-causing mutations in the CFTR gene have not been identified in any nonhuman animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans (e.g., bronchiectasis and pancreatitis), we hypothesized that dogs with these disorders likely have a higher expression...
Article
Deafness in dogs is frequently associated with the pigment genes piebald and merle. Little is known about the prevalence of deafness in dogs carrying the merle allele. To determine the prevalence of deafness in dogs heterozygous and homozygous for the merle allele of the mouse Silver pigment locus homolog (SILV) gene. One hundred and fifty-three pr...
Article
Harlequin is a coat pattern of the Great Dane characterized by ragged patches of full color on a white background. Harlequin patterning is a bigenic trait, resulting from the interaction of the merle allele of SILV, and a dominant modifier locus, H. Breeding data suggest that H is embryonic recessive lethal and that all harlequins are Hh. To identi...
Article
The German shepherd dog (GSD) is a preferred choice of many law enforcement and military agencies across the world. Unfortunately, the breed is afflicted with approximately 50 hereditary diseases. Seven major diseases afflicting the GSD are described herein: pancreatic acinar atrophy, megaesophagus, hip dysplasia, degenerative myelopathy, hemophili...
Article
Dermatomyositis (DM) is a canine and human inflammatory disease of the skin and muscle that is thought to be autoimmune in nature. In dogs, DM occurs most often in the rough collie and Shetland sheepdog. Characteristic skin lesions typically develop on the face, ears, tail, and distal extremities. The severity of lesions varies and is thought to in...
Chapter
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Short interspersed elements (SINEs) are mobile elements that contribute to genomic diversity through the addition of genetic material. Recent genomic analyses have vastly augmented our knowledge of both human- and canine-specific SINEs. SINEC_Cf is a major SINE of the canid family that has undergone recent expansion and is thought to be present in...
Article
Full-text available
Animal models are requisite for genetic dissection of, and improved treatment regimens for, human hereditary diseases. While several animals have been used in academic and industrial research, the primary model for dissection of hereditary diseases has been the many strains of the laboratory mouse. However, given its greater (than the mouse) geneti...
Article
Full-text available
Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red-yellow pheomelanin vs. black-brown eu...
Article
Full-text available
Merle is a pattern of coloring observed in the coat of the domestic dog and is characterized by patches of diluted pigment. This trait is inherited in an autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous for the merle locus exhibit a wide range of auditory and ophthalmologic abnormalities, which are similar to those observed...
Article
Dermatomyositis is an inflammatory disease of the skin and muscle and is most commonly found in the Shetland sheepdog. Both the clinical presentation and the age of onset of dermatomyositis vary widely, and the inability to diagnose dermatomyositis before clinical symptoms ensue has made control of the disease difficult. Identification of a genetic...
Article
Pancreatic acinar atrophy (PAA) is a degenerative disease of the exocrine pancreas and is the most common cause of exocrine pancreatic insufficiency in the German Shepherd Dog. Analyses of inheritance have shown that a single gene segregating in an autosomal recessive fashion is causative for PAA. To date the gene and causative mutation have not be...
Article
To develop a set of microsatellite markers, composed of a minimal number of these markers, suitable for use in forensic genetic investigations in dogs. Blood, tissue, or buccal epithelial cells from 364 dogs of 85 breeds and mixed breeds and 19 animals from related species in the family Canidae. 61 tetranucleotide microsatellite markers were charac...
Article
To expedite linkage studies and positional cloning efforts in the dog, Minimal Screening Set 2 (MSS-2) of 327 canine microsatellite markers has been multiplexed into chromosome-specific panels. MSS-2 provides 9 Mb coverage of the canine genome with no gaps larger than 17.1 Mb and is the most recent and comprehensive set of microsatellites available...
Article
Full-text available
There is incredible morphological and behavioral diversity among the hundreds of breeds of the domestic dog, CANIS FAMILIARIS. Many of these breeds have come into existence within the last few hundred years. While there are obvious phenotypic differences among breeds, there is marked interbreed genetic homogeneity. Thus, study of canine genetics an...
Article
To assess the heritability of pancreatic acinar atrophy (PAA) in German Shepherd Dogs (GSDs) in the United States. 135 GSDs belonging to 2 multigenerational pedigrees. Two multigenerational pedigrees of GSDs with family members with PAA were identified. The clinical history of each GSD enrolled in the study was recorded, and serum samples for canin...
Article
A set of 172 canine microsatellite markers, termed minimal screening set 1 (MSS1), was recently characterized for use in whole-genome screens. We report here the multiplexing of 155 MSS1 markers into 48 multiplex sets. Amplification of the multiplex sets is achieved using a single thermal cycling program. The markers are labeled with fluorescent dy...
Article
The domestic dog, Canis lupus familiaris, has emerged as a model system for the study of human hereditary diseases. Of the approximately 450 hereditary diseases described in the dog, half have clinical presentations that are quite similar to specific human diseases. Understanding the genetic bases of canine hereditary diseases will not only complem...

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