Haplotype analysis of the MDR1 flanking region in the dog breed Elo

A deletion mutation in the canine multidrug resistance (MDR1) gene provokes drug sensitivity in several dog breeds from the Collie lineage. A haplotype of four microsatellites containing this mdr1-1Delta mutation was conserved among affected breeds. In this study, we analysed the haplotypes of the MDR1 flanking region of 177 dogs of the breed Elo which is composed of several dog breeds including the Old English sheepdog from the Collie lineage. We detected a haplotype in the Elo breed which had previously been associated with the mutant mdr1-1Delta allele in Old English sheepdogs. Using a regression analysis for the probability of the haplotype on the proportion of genes of the founder breeds, we could exclude the Old English sheepdog as origin of this haplotype for the Elo breed. The MDR1 flanking region could be traced back to the Japanese Spitz as one of the founder dog breeds of the Elo and thus, the introgression of the mdr1-1Delta mutation into the dog breed Elo through the Collie lineage is very unlikely.     

Population structure and genetic differentiation of livestock guard dog breeds from the Western Balkans

Livestock guard dog (LGD) breeds from the Western Balkans are a good example of how complex genetic diversity pattern observed in dog breeds has been shaped by transition in dog breeding practices. Despite their common geographical origin and relatively recent formal recognition as separate breeds, the Karst Shepherd, Sarplaninac and Tornjak show distinct population dynamics, assessed by pedigree, microsatellite and mtDNA data. We genotyped 493 dogs belonging to five dog breeds using a set of 18 microsatellite markers and sequenced mtDNA from 94 dogs from these breeds. Different demographic histories of the Karst Shepherd and Tornjak breeds are reflected in the pedigree data with the former breed having more unbalanced contributions of major ancestors and a realized effective population size of less than 20 animals. The highest allelic richness was found in Sarplaninac (5.94), followed by Tornjak (5.72), whereas Karst Shepherd dogs exhibited the lowest allelic richness (3.33). Similarly, the highest mtDNA haplotype diversity was found in Sarplaninac, followed by Tornjak and Karst Shepherd, where only one haplotype was found. Based on F_ST differentiation values and high percentages of animals correctly assigned, all breeds can be considered genetically distinct. However, using microsatellite data, common ancestry between the Karst Shepherd and Sarplaninac could not be reconstructed, despite pedigree and mtDNA evidence of their historical admixture. Using neighbour‐joining, STRUCTURE or DAPC methods, Sarplaninac and Caucasian Shepherd breeds could not be separated and additionally showed close proximity in the NeighborNet tree. STRUCTURE analysis of the Tornjak breed demonstrated substructuring, which needs further investigation. Altogether, results of this study show that the official separation of these dog breeds strongly affected the resolution of genetic differentiation and thus suggest that the relationships between breeds are not only determined by breed relatedness, but in small populations even more importantly by stochastic effects.     

Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping

OBJECTIVE: To evaluate the breed distribution of the ABCB1-1Delta polymorphism in a large number of dogs in North America, including dogs of several herding breeds in which this polymorphism has been detected and other breeds in which this polymorphism has not yet been identified. DESIGN: Cross-sectional study. ANIMALS: 5,368 dogs from which buccal swab samples were collected for purposes of ABCB1 genotyping. PROCEDURES: From May 1, 2004, to September 30, 2007, DNA specimens derived from buccal swab samples collected from 5,368 dogs underwent ABCB1 genotyping. These data were reviewed, and results for each dog were recorded in a spreadsheet, along with the dog's breed. The genotypes for each breed were tallied by use of a sorting function. RESULTS: The ABCB1-1Delta allele was identified in 9 breeds of dogs and in many mixed-breed dogs. Breeds that had the ABCB1-1Delta allele included Collie, Longhaired Whippet, Australian Shepherd (standard and miniature), Shetland Sheepdog, Old English Sheepdog, Border Collie, Silken Windhound, and German Shepherd Dog (a breed in which this mutation had not been detected previously). CONCLUSIONS AND CLINICAL RELEVANCE: The ABCB1-1Delta polymorphism is associated with increased susceptibility to many adverse drug reactions and with suppression of the hypothalamic-pituitary-adrenal axis and is present in many herding breeds of dog. Veterinarians should be familiar with the breeds that have the ABCB1-1Delta polymorphism to make appropriate pharmacologic choices for these patients.     

Review of prevalence, genetic aspects and adverse effects of the mdr1-1Delta mutation in dogs

A mutation in the canine MDR1 gene causes multiple drug sensitivity in dog breeds of the Collie lineage. Dogs with this genetic defect show severe neurotoxic adverse effects if they are treated with particular drugs. Clinical signs depending on the administered drug and its concentration vary from mild toxicosis with salivation and disorientation to severe effects with coma and finally death of the dog. Drugs which provoke adverse effects are structurally different. Although they are used for many different indications, all of these drugs are substrates of a transporting protein encoded by the MDR1 gene.This P-glycoprotein loses its normal protecting function at the tissue barriers in dogs with the mdrl-1Delta mutation.This article gives a short overview about the present state of analyses regarding the canine MDR1 gene.The genetic background, effects and prevalence in affected dog breeds of the mdrl-1Delta mutation are summarized. On the one hand, the overview might help practical veterinarians to understand the aetiology of drug sensitivity in dogs with the mdrl-1Delta mutation, and on the other hand, it might point out appendages for future research works about the canine MDR1 gene as well as for breeding strategies in affected dog breeds.     

Analysis of the canine mdr1-1Delta mutation in the dog breed Elo

A deletion mutation in the canine multidrug resistance gene, MDR1, is associated with drug sensitivity. This was shown for several purebred dog breeds from the Collie lineage such as the Collie (rough-coated and smooth-coated), the Australian Shepherd and the Old English sheepdog. To determine whether the mdr1-1Delta mutation could be found in the newly bred German dog breed Elo which is based amongst other breeds on Old English sheepdogs, 177 blood samples representative for the Elo breed were collected. After DNA extraction, a polymerase chain reaction-based method with subsequent polyacrylamide gel electrophoresis was used for detection of the mdr1-1Delta mutation. The mdr1-1Delta allele was not observed in the Elos investigated. The probability that the mdr1-1Delta allele originated in the Old English sheepdog breed is segregating in the Elo population was estimated at 3.68 x 10(-17).     

Androgen receptor CAG repeat polymorphisms in canine prostate cancer

Background: Relatively shorter lengths of the polymorphic polyglutamine repeat‐1 of the androgen receptor (AR) have been associated with an increased risk of prostate cancer (PC) in humans. In the dog, there are 2 polymorphic CAG repeat (CAGr) regions. Objective: To investigate the relationship of CAGr length of the canine AR‐gene and the development of PC. Animals: Thirty‐two dogs with PC and 172 control dogs were used. Methods: DNA was extracted from blood. Both CAG repeats were amplified by polymerase chain reaction (PCR) and PCR products were sequenced. Results: In dogs with PC, CAG‐1 repeat length was shorter (P= .001) by an increased proportion of 10 repeats (P= .011) and no 12 repeats (P= .0017) than in the control dogs. No significant changes were found in CAG‐3 length distribution. CAG‐1 and CAG‐3 polymorphisms proved not to be in linkage disequilibrium. Breed difference in allelic distribution was found in the control group. Of the prostate‐disease sensitive breeds, a high percentage (64.5%) of the shortest haplotype 10/11 was found in the Doberman, whereas Beagles and German Pointers had higher haplotype 12/11 (47.1 and 50%). Bernese Mountain dogs and Bouvier dogs both shared a high percentage of 11 CAG‐1 repeats and 13 CAG‐3 repeats. Differences in (combined) allelic distributions among breeds were not significant. Conclusions and Clinical Importance: In this preliminary study, short CAG‐1 repeats in the AR‐gene were associated with an increased risk of developing canine PC. Although breed‐specific differences in allelic distribution of CAG‐1 and CAG‐3 repeats were found, these could not be related to PC risk.     

Genetic analysis of optic nerve head coloboma in the Nova Scotia Duck Tolling Retriever identifies discordance with the NHEJ1 intronic deletion (collie eye anomaly mutation)

Collie eye anomaly (CEA) encompasses a spectrum of different ophthalmic phenotypes from clinically inconsequential choroidal hypoplasia to blindness from coloboma of the optic nerve head (ONH). A previous study found a 7.8‐kb deletion in intron 4 of the NHEJ1 gene to be associated with CEA. A genetic test based on this association is recommended for many breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR). Collection of ONH coloboma‐affected NSDTR showed lack of concordance of the NHEJ1 intronic deletion with ONH coloboma. Using genomewide single nucleotide polymorphism (SNP) genotyping in 7 ONH coloboma‐affected NSDTR cases and 47 unaffected NSDTR controls with no ophthalmic signs, one SNP, located on chromosome 7, demonstrated genomewide significance. However, high genomic inflation may have confounded the results. Therefore, the genomewide association study was repeated using EMMAX to control for population structure in the cohort of 7 cases and 47 controls. However, no regions of the genome were significantly associated with ONH coloboma. These results failed to document significant association with the CEA locus. Due to the complex genetic etiology of ONH coloboma, the NHEJ1 intronic deletion test results should be carefully considered when making breeding decisions. If the goal is to select for visually competent dogs, our data suggest that eye examinations of puppies would be more effective as a guide in selection of breeding pairs than relying solely on currently available genetic tests.     

A truncated retrotransposon disrupts the GRM1 coding sequence in Coton de Tulear dogs with Bandera's neonatal ataxia

Background: Bandera's neonatal ataxia (BNAt) is an autosomal recessive cerebellar ataxia that affects members of the Coton de Tulear dog breed. Objective: To identify the mutation that causes BNAt. Animals: The study involved DNA from 112 Cotons de Tulear (including 15 puppies with signs of BNAt) and 87 DNA samples from dogs of 12 other breeds. Methods: The BNAt locus was mapped with a genome‐wide association study (GWAS). The coding exons of positional candidate gene GRM1, which encodes metabotropic glutamate receptor 1, were polymerase chain reaction (PCR)‐amplified and resequenced. A 3‐primer PCR assay was used to genotype individual dogs for a truncated retrotransposon inserted into exon 8 of GRM1. Results: The GWAS indicated that the BNAt locus was in a canine chromosome 1 region that contained candidate gene GRM1. Resequencing this gene from BNAt‐affected puppies indicated that exon 8 was interrupted by the insertion of a 5′‐truncated retrotransposon. All 15 BNAt‐affected puppies were homozygous for the insert, whereas all other Cotons de Tulear were heterozygotes (n = 43) or homozygous (n = 54) for the ancestral allele. None of the 87 dogs from 12 other breeds had the insertion allele. Conclusions and Clinical Importance: BNAt is caused by a retrotransposon inserted into exon 8 of GRM1. A DNA test for the GRM1 retrotransposon insert can be used for genetic counseling and to confirm the diagnosis of BNAt.     

Use of amnion and placenta in neonatal screening for canine GM1-gangliosidosis and the risk of diagnostic misclassifications

BACKGROUND: A closed breeding colony of Shiba dogs with GM1-gangliosidosis is maintained at Hokkaido University (Sapporo, Japan). Neonatal genotyping is essential to control the breeding colony genetically as an animal model for the human disease. OBJECTIVES: The purpose of the present study was to determine the utility of amnion and placenta in the neonatal screening or diagnosis for canine GM1-gangliosidosis. METHODS: Twenty neonatal Shiba dogs of a pedigree with GM1- gangliosidosis were differentiated into 3 genotypes--normal, heterozygous, and affected dogs--by using a previously reported DNA mutation assay. Acid beta-galactosidase activity was measured in amnion and placenta and compared among the 3 genotypes. RESULTS: The level of beta-galactosidase activity in the amnion of affected dogs was negligible and <2% of the mean activity in normal dogs; there was no significant difference among the 3 genotypes. In placenta, beta-galactosidase activity was significantly different among all the genotypes; however, there was wide overlap in enzyme activity between normal and heterozygous dogs. The level of activity in affected dogs was relatively high and >10% of the mean activity in normal dogs. The DNA mutation assay gave correct information about genotype with genomic DNA extracted from amnion but ambiguous information with DNA from placenta. CONCLUSIONS: Amnion and placenta were not useful as enzyme sources in neonatal screening in canine GM1-gangliosidosis because of the risk of misdiagnosis. DNA from amnion is applicable as a template for genotyping, whereas placenta should not be used because canine placenta contains maternal cells.     

Comparison of the hypothalamic–pituitary–adrenal axis in MDR1-1Δ and MDR1 wildtype dogs

Objective: To evaluate the hypothalamic–pituitary–adrenal (HPA) axis in MDR1‐1Δ (dogs with the MDR1 mutation associated with ivermectin sensitivity) and MDR1 wildtype dogs. Design: Prospective study. Setting: Institutional vivarium. Animals: Seven healthy Collie dogs. Measurements: MDR1 genotyping was used for allocation of dogs to 1 of 2 groups: dogs homozygous for the wildtype MDR1 allele (MDR1 wildtype) and those homozygous for the MDR1‐1Δ mutation (MDR1 mutant). Blood samples were obtained for determination of cortisol and adrenocorticotropin hormone (ACTH) concentrations under basal conditions, before and after ACTH administration, and before and after dexamethasone administration. Main results: Significant differences were identified between the MDR1 mutant and MDR1 wildtype groups. Basal plasma cortisol concentrations and cortisol concentrations after ACTH administration were significantly lower in MDR1 mutant dogs as compared with MDR1 wildtype dogs. Plasma ACTH concentrations after dexamethasone administration were significantly lower in MDR1 mutant dogs as compared with MDR1 wildtype dogs. Conclusions: Results suggest that P‐glycoprotein (P‐gp) plays a role in regulation of the HPA axis. Furthermore, it appears that the HPA axis in MDR1 mutant dogs that lack P‐gp is suppressed compared with MDR1 wildtype dogs. This finding may explain some clinical observations in breeds known to harbor the MDR1 mutation including Collies, Shelties, Australian Shepherds, and others. There is a clinical impression that many of these dogs have worse outcomes in response to stress and, at times, respond poorly to appropriate therapy. HPA axis suppression, secondary to the MDR1 mutation, could result in a relative adrenal insufficiency (RAI) state during times of stress or illness. Further studies are required to determine the relationship between the MDR1 genotype and RAI.     

Retinal Disease in the N.Z. Working Dog

Sir, — It may be of interest to some rural practitioners, having an upsurge in requests for opthalmoscopic examinations of working dogs, to know that at present this practice is engaged in examinations at the National dog trials. Retinal disease is an increasing problem in both Huntaways and Heading dogs in this country. This is probably a result of the extensive use of selected strains and the tendency for the breeds to become more uniform with farmers keeping fewer better-bred dogs. Work on this complex condition is however in its infancy, and a great deal is yet to be resolved. At this stage histological sectioning suggests an inflammatory component, but computer pedigree analysis suggests a heretibility of 0.33 — 0.40. In the main the condition is not analogous to central P.R.A. present in the British Border Collie, despite its ancestral contribution particularly to the Heading dog.     

Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of herding breed dogs living in Australia

A study was performed to determine the frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample of Collies and other herding breeds living in Australia. Buccal swab samples were collected from 33 Collies, 17 Australian Shepherds, 7 Border Collies and 7 Shelties for determination of MDR1 genotype. DNA was extracted and the polymerase chain reaction was performed to amplify a 148 base pair (wildtype MDR1 genotype or 144 base pair (mutant MDR1 genotype) amplicon containing the MDR1 mutation. Sequence analysis was performed to determine the genotype of each dog. Adequate quantities of DNA for unequivocal genotyping were obtained from 61 of 64 samples. The previously described MDR1 mutation was identified in Collies, Australian Shepherds and Shelties living in Australia, but not in Border Collies (although sample numbers were low). Twelve percent (4/33) of the Collies studied were homozygous for the normal allele (normal), 64% (21/33) were heterozygous (carrier) and 24% (8/33) were homozygous for the mutant allele (affected). Results of this study indicate that a high percentage of herding breeds presenting to veterinarians in Australia harbor the MDR1 mutation, thus impacting some therapeutic decisions.     

ADAMTS17 mutation associated with primary lens luxation is widespread among breeds

Primary lens luxation (PLL) is a well-recognized, painful and potentially blinding inherited ocular condition in dogs. We screened PLL-affected dogs of 30 different breeds, to identify those which carried a previously described c.1473+1 G>A mutation in ADAMTS17 that is associated with PLL in Miniature Bull terriers, Lancashire Heelers, and Jack Russell terriers. This ADAMTS17 mutation was identified in PLL-affected dogs from 14 additional breeds. PLL-affected dogs from some breeds (most notably the Shar pei and the Brittany spaniel) did not carry the G1473+1A ADAMTS17 mutation, indicating they must suffer from a genetically distinct form of the condition. We also estimated the frequency of this ADAMTS17 mutation in some of the breeds. Our findings indicate the mutation segregates in a large number of different breeds of dog, many of which are terriers or breeds with terrier co-ancestry, but some of which have more diverse origins. Our results also indicate that the mutation is present at high frequency within most of the breeds in which it segregates. In the miniature bull terrier breed estimates of mutation frequency ranged from 0.27 to 0.39, corresponding to 7.3-15.2% PLL-affected dogs in this breed. We also identified an increased risk of PLL associated with heterozygosity at ADAMTS17, suggesting that carriers carry a low risk of developing PLL.     

Familial canine pituitary-dependent hyperadrenocorticism in wirehaired Dachshunds

Canine pituitary hyperadrenocorticism (Cushing's disease) caused by neoplasia of the corticotrope cells is one of the most common endocrine diseases especially in smaller dog breeds. Cushing's disease was diagnosed in eleven wire-haired Dachshunds and for further six wire-haired Dachshunds Cushing's disease was suspected on the basis of clinical signs. A joined pedigree could be ascertained for all these 17 dogs. Eleven of these dogs were so closely related to each other, that they were summarized in four nucleus families. Two fullsiblings were examined by means of clinical, laboratory diagnostic and morphological methods. The main lesions consisted of atrophic dermatosis with alopecia, increase of activity of liver enzymes in plasma and bilateral adrenocortical hyperplasia and therefore corresponded to the typical signs of a secondary hyperadrenocorticism. A rather unusual finding was the pituitary carcinoma in one of these dogs. Similarly to human patients affected by hyperadrenocorticism, real-time PCR analysis showed a 2.9-fold increase of expression of the canine MDR1 gene in the liver of one affected wirehaired Dachshund. This study documents the first familial occurrence of pituitary-dependent hyperadrenocorticism in wirehaired Dachshunds, the overexpression of the MDR1 gene in the dog and the third case of familial hyperadrenocorticism in dogs ever described.     

Evaluation of canine heat shock transcription factor 4 (HSF4) as a candidate gene for primary cataracts in the Dachshund and the Entlebucher Mountain dog

OBJECTIVE: Testing of the cataract-causing insertion/deletion mutation in the canine HSF4 gene for its linkage and association with primary cataracts (CAT) in Dachshunds and Entlebucher Mountain dogs. MATERIALS: Exon 9 with flanking intronic regions of the canine HSF4 gene was sequenced in 24 Dachshunds and 20 Entlebucher Mountain dogs. The HSF4 cDNA sequence of lens tissue was analyzed in a CAT-unaffected mixed-breed dog and in three CAT-affected dogs of different breeds, including a Wire-haired Dachshund, a Dachshund-mix and a German Shepherd dog. RESULTS: In all dogs investigated here, the previously reported CAT-causing mutation did not exist. We found a single nucleotide polymorphism (SNP) in intron 9, which was neither associated nor linked with the CAT phenotype in the two dog breeds. CONCLUSION: The CAT phenotype in the two dog breeds investigated here was not caused by the same mutation found to be associated with early-onset CAT in the Staffordshire Bull Terrier and Boston Terrier. The intronic SNP may be useful to test HSF4 for linkage with CAT in further dog breeds.     

Retinal degeneration in nine Swedish Jämthund dogs

The Jämthund is the fourth most common breed in Sweden with approximately 1600 pups registered each year. Although it has been known that some adult dogs go blind, so they cannot hunt, the Jämthund dog has historically not been screened for hereditary eye diseases. This report describes nine Swedish Jämthund dogs with retinal degeneration. These dogs represent all Jämthund dogs diagnosed with progressive retinal atrophy (PRA) by the Swedish Eye Panel and registered with the Swedish Kennel Club from January 1998 to September 2008. The dogs were examined with indirect opthalmoscopy and slitlamp biomicroscopy. Additionally, electroretinograms (ERGs) following ECVO guidelines were performed in two dogs (one affected and one normal) and the eyes from three affected dogs were examined by light‐microscopy postmortem. Typical findings were bilateral symmetric generalized retinal degeneration with tapetal hyper‐reflectivity, attenuation of blood vessels and pigment clumping in the nontapetal fundus. These retinal findings progressed with time in two dogs after re‐examination. Visual impairment, especially under dim light conditions, was observed in the affected dogs. ERG from one affected dog showed profoundly reduced rod responses, whereas cone responses were better preserved. Microscopic changes in the eyes from three dogs were characterized by a severe diffuse predominantly outer retinal degeneration and atrophy. Re‐sequencing of the prcd‐gene for eight of the nine investigated dogs revealed that none of the individuals carried disease allele that has been associated with prcd‐PRA in other breeds. In conclusion, ophthalmoscopic, electroretinographic, and light‐microscopic alterations observed in nine Jämthund dogs were compatible with PRA. The prcd mutation was excluded as a cause of this retinopathy.     

Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings

Trapped neutrophil syndrome (TNS) is an autosomal recessive inherited neutropenia known in Border Collies since the 1990's. Recently, the causative mutation has been identified in the canine VPS13B gene and a DNA-based diagnosis has now become available. The present paper describes clinical and clinico-pathologic findings in a Border Collie with TNS that was molecularly diagnosed for the first time in Japan. In a 10-week-old male Border Collie with microgenesis and symptoms related to recurrent infections, a hematological examination revealed severe leukopenia due to neutropenia, suggesting the dog to be affected by inherited neutropenic immunodeficiency. Direct DNA sequencing demonstrated that the dog was homozygous for the causative mutation of TNS and both its parents were heterozygous carriers. In addition, a simple and rapid polymerase chain reaction-based length polymorphism analysis coupled with microchip electrophoresis was developed for the genotyping of TNS. This assay could discriminate clearly all genotypes, suggesting that it was suitable for both individual diagnosis and large-scale surveys for prevention.     

Allele-specific polymerase chain reaction diagnostic test for the functional MDR1 polymorphism in dogs

The major multidrug transporter P-glycoprotein (Pgp) contributes to the barrier function of several tissues and organs, including the brain. In a subpopulation of Collies and seven further dog breeds, a 4 base pair deletion has been described in the Pgp-encoding MDR1 gene. This deletion results in the absence of a functional form of Pgp and loss of its protective function. Severe intoxication with the Pgp substrate ivermectin has been attributed to the genetically determined lack of Pgp. An allele-specific polymerase chain reaction (PCR)-based screening method has been developed to detect the mutant allele and to determine if a dog is homozygous or heterozygous for the mutation. Based on this validation, the allele-specific PCR proved to be a robust, reproducible and specific tool, allowing rapid determination of the MDR1 genotype of dogs of at risk breeds using blood samples or buccal swabs.     

Primary lens luxation in the Chinese Shar Pei: clinical and hereditary characteristics

A pedigree analysis of a family of 15 related Chinese Shar Peis was conducted. This pedigree analysis, including affected and nonaffected dams, sires and offspring, was compiled to document and characterize the occurrence, common clinical signs, and age of onset of primary lens luxation while suggesting a possible mode of inheritance in this breed. Of the five offspring from the mating of an affected dam to two unrelated affected males, 100% of offspring were affected with bilateral primary lens luxations. Of the four viable offspring from the mating of the same affected dam to an unrelated, unaffected male, two dogs (50%) were affected. The average age of onset of affected animals (seven) in this first generation was 4.9 years (range 3–6 years). The six dogs in the second generation of the same pedigree line were 2-years-old at examination with none of these animals affected at the time of this study. The most common presenting complaints were a unilateral change in ocular appearance (5 of 7 dogs) and subjective vision impairment (4 of 7 dogs). The most common clinical sign upon ophthalmic examination was iridodonesis (unilateral 4 of 7 dogs; bilateral 3 of 7 dogs) and the presence of an aphakic crescent (3 of 7 dogs). Gonioscopy and tonometry of severely affected eyes revealed a narrow or closed iridocorneal angle and ocular hypertension. This study suggests that primary lens luxation does occur in the Chinese Shar Pei, resembling the clinical condition (age of onset, clinical signs) previously described in the terrier breeds, the Border Collie, and the Tibetan Terrier. Application of the phenotypic findings in this study to a Mendelian genetic model of inheritance suggests that primary lens luxation in the Chinese Shar Pei is inherited as a simple autosomal recessive trait.