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Deficient homozygosity of a variant maintained in a population suggests that the variant may be embryonic lethal. We examined whole genome sequence data from 675 canids to investigate for variants with missing homozygosity and high predicted impact. Our analysis identified 45 variants, in 32 genes. However, further scrutiny of the sequence reads revealed that all but one of these variants were artifacts of the variant calling process when using CanFam3.1, a widely utilized canine reference genome. We demonstrate that the use of multiple, newer reference genomes could reduce artifacts and lead to more accurate variant identification.

An idiopathic epilepsy (IE) risk haplotype on canine chromosome (CFA) 14 has been reported to interact with the CFA37 common risk haplotype in the Belgian shepherd (BS). Additional IE cases and control dogs were genotyped for the risk haplotypes to validate these previous findings. In the new cohort, the interaction between the two regions significantly elevated IE risk. When the haplotypes were analyzed individually, particular haplotypes on both CFA14 (ACTG) and 37 (GG) were associated with elevated IE risk, though only the CFA37 AA was significantly associated (

Background Primary hypoadrenocorticism (or Addison’s disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency. The disease has been described in purebred and mixed breed dogs, although some breeds, including the Bearded Collie, are at increased risk for AD. Candidate gene approaches have yielded few associations that appear to be breed-specific. A single other genome-wide association study reported no significant regions of association for AD in Standard Poodles. The present study aimed to identify genomic regions of association for canine AD in Bearded Collies. Results Our study consists of the first genome-wide association analysis to identify a genome-wide significant region of association with canine AD (CFA18). Peaks of suggestive association were also noted on chromosomes 11, 16 and 29. Logistic regression analysis supported an additive effect of risk genotypes at these smaller effect loci on the probability of disease associated with carrying a risk genotype on CFA18. Potential candidate genes involved in adrenal steroidogenesis, regulation of immune responses and/or inflammation were identified within the associated regions of chromosomes 11 and 16. The gene-poor regions of chromosomes 18 and 29 may, however, harbor regulatory sequences that can modulate gene expression and contribute to disease susceptibility. Conclusion Our findings support the polygenic and complex nature of canine AD and identified a strongly associated locus on CFA18 that, when combined with three other smaller effect loci, was predictive of disease. The results offer progress in the identification of susceptibility loci for canine AD in the Bearded Collie. Further studies are needed to confirm association with the suggested candidate genes and identify actual causative mutations involved with AD susceptibility in this breed.

Background Idiopathic epilepsy (IE) is a common neurological disorder in the domestic dog, and is defined as repeated seizure activity having no identifiable underlying cause. Some breeds, such as the Belgian shepherd dog, have a greater prevalence of the disorder. Previous studies in this and other breeds have identified ADAM23 as a gene that confers risk of IE, although additional loci are known to exist. The present study sought to identify additional loci that influence IE in the Belgian shepherd dog. Results Genome-wide association studies (GWAS) revealed a significant association between IE and CFA 14 (p − 08) and a suggestive association on CFA 37 (p − 06) in a region in linkage disequilibrium with ADAM23. Logistic regression identified a 2-loci model that demonstrated interaction between the two chromosomal regions that when combined predicted IE risk with high sensitivity. Conclusions Two interacting loci, one each on CFAs 14 and 37, predictive of IE in the Belgian shepherd were identified. The loci are adjacent to potential candidate genes associated with neurological function. Further exploration of the region is warranted to identify causal variants underlying the association. Additionally, although the two loci were very good at predicting IE, they failed to capture all the risk, indicating additional loci or incomplete penetrance are also likely contributing to IE expression in the Belgian shepherd dog.

Funder: Italian Spinone Club of Great Britain, Funder: Kennel Club Charitable Trust, Genotype imputation using a reference panel that combines high-density array data and publicly available whole genome sequence consortium variant data is potentially a cost-effective method to increase the density of extant lower-density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed-specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R2 = 0.94) and the highest for the Italian Spinone dataset (mean R2 = 0.97). This study's findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed-specific array data and multi-breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed-specific data, is described in detail to facilitate and encourage use of this technique in canine genetics.

This study focuses on the trust that potential jurors have in unsubstantiated evidence and the implications of such trust for legal decision-making. We examined whether participants’ motivation to ...

The Covid-19 pandemic served as the impetus to implement activities designed to engage students in the remote instructional environment while simultaneously developing scientific literacy skills. In a high enrollment general education animal science course, numerous activities were designed to improve scientific literacy. These included specifically developed videos covering strategies for reading published science literature, the utilization of topically relevant scientific articles that captured student interest, and engaging students in a citizen science exercise on whether dogs align themselves to the Earth's magnetic field during excretion behavior. Employing pre- and post-self-perception surveys coupled with tasking students to apply their scientific literacy skills in an assessment scenario demonstrated that students' self-perception of their scientific literacy improved 30% (P < 0.05) with approximately 80% of students accurately applying their literacy skills. The citizen science study on excretory behavior was modeled on previously published findings thereby providing an opportunity to validate the published work which had indicated that dogs align their bodies in a North–South axis during excretion. The present study did not demonstrate preferential alignment to any geomagnetic orientation which emphasized to the students the need for scientific replication. Inclusion of simple activities that were relevant to students' daily lives, and providing interpretive context for those activities, resulted in improved self-perceived scientific literacy.

Sole ulcers (SUs) and white line disease (WLD) are two common noninfectious claw lesions (NICL) that arise due to a compromised horn production and are frequent causes of lameness in dairy cattle, imposing welfare and profitability concerns. Low to moderate heritability estimates of SU and WLD susceptibility indicate that genetic selection could reduce their prevalence. To identify the susceptibility loci for SU, WLD, SU and/or WLD, and any type of noninfectious claw lesion, genome-wide association studies (GWAS) were performed using generalized linear mixed model (GLMM) regression, chunk-based association testing (CBAT), and a random forest (RF) approach. Cows from five commercial dairies in California were classified as controls having no lameness records and ≥6 years old (n = 102) or cases having SU (n = 152), WLD (n = 117), SU and/or WLD (SU + WLD, n = 198), or any type of noninfectious claw lesion (n = 217). The top single nucleotide polymorphisms (SNPs) were defined as those passing the Bonferroni-corrected suggestive and significance thresholds in the GLMM analysis or those that a validated RF model considered important. Effects of the top SNPs were quantified using Bayesian estimation. Linkage disequilibrium (LD) blocks defined by the top SNPs were explored for candidate genes and previously identified, functionally relevant quantitative trait loci. The GLMM and CBAT approaches revealed the same regions of association on BTA8 for SU and BTA13 common to WLD, SU + WLD, and NICL. These SNPs had effects significantly different from zero, and the LD blocks they defined explained a significant amount of phenotypic variance for each dataset (6.1–8.1%, p < 0.05), indicating the small but notable contribution of these regions to susceptibility. These regions contained candidate genes involved in wound healing, skin lesions, bone growth and mineralization, adipose tissue, and keratinization. The LD block defined by the most significant SNP on BTA8 for SU included a SNP previously associated with SU. The RF models were overfitted, indicating that the SNP effects were very small, thereby preventing meaningful interpretation of SNPs and any downstream analyses. These findings suggested that variants associated with various physiological systems may contribute to susceptibility for NICL, demonstrating the complexity of genetic predisposition.

The dog has assumed a prominent role in human society. Associated with that status, diet choices for companion dogs have begun to reflect the personal preferences of the owners, with greater emphasis on specialty diets such as organic, vegan/vegetarian, and omission or inclusion of specific ingredients. Despite consumer preferences and many marketing strategies employed, the diets must ensure nutritional adequacy for the dog; if not, health becomes compromised, sometimes severely. The most frequent consideration of consumers and dog food manufacturers is protein source and concentration with a growing emphasis on amino acid composition and bioavailability. Amino acids in general play diverse and critical roles in the dog, with specific amino acids being essential. This review covers what is known regarding amino acids in dog nutrition.

The dog has assumed a prominent role in human society. Associated with that status, diet choices for companion dogs have begun to reflect the personal preferences of the owners, with greater emphasis on specialty diets such as organic, vegan/vegetarian, and omission or inclusion of specific ingredients. Despite consumer preferences and many marketing strategies employed, the diets must ensure nutritional adequacy for the dog; if not, health becomes compromised, sometimes severely. The most frequent consideration of consumers and dog food manufacturers is protein source and concentration with a growing emphasis on amino acid composition and bioavailability. Amino acids in general play diverse and critical roles in the dog, with specific amino acids being essential. This review covers what is known regarding amino acids in dog nutrition.

An amendment to this paper has been published and can be accessed via the original article.

Digital dermatitis (DD) causes lameness in dairy cattle. To detect the quantitative trait loci (QTL) associated with DD, genome-wide association studies (GWAS) were performed using high-density single nucleotide polymorphism (SNP) genotypes and binary case/control, quantitative (average number of FW per hoof trimming record) and recurrent (cases with &ge, 2 DD episodes vs. controls) phenotypes from cows across four dairies (controls n = 129 vs. FW n = 85). Linear mixed model (LMM) and random forest (RF) approaches identified the top SNPs, which were used as predictors in Bayesian regression models to assess the SNP predictive value. The LMM and RF analyses identified QTL regions containing candidate genes on Bos taurus autosome (BTA) 2 for the binary and recurrent phenotypes and BTA7 and 20 for the quantitative phenotype that related to epidermal integrity, immune function, and wound healing. Although larger sample sizes are necessary to reaffirm these small effect loci amidst a strong environmental effect, the sample cohort used in this study was sufficient for estimating SNP effects with a high predictive value.

In dogs, symmetrical lupoid onychodystrophy (SLO) results in nail loss and an abnormal regrowth of the claws. In Bearded Collies, an autoimmune nature has been suggested because certain dog leukocyte antigen (DLA) class II haplotypes are associated with the condition. A genome-wide association study of the Bearded Collie revealed two regions of association that conferred risk for disease: one on canine chromosome (CFA) 12 that encompasses the DLA genes, and one on CFA17. Case-control association was employed on whole genome sequencing data to uncover putative causative variants in SLO within the CFA12 and CFA17 associated regions. Genotype imputation was then employed to refine variants of interest. Although no SLO-associated protein-coding variants were identified on CFA17, multiple variants, many with predicted damaging effects, were identified within potential candidate genes on CFA12. Furthermore, many potentially damaging alleles were fully correlated with the presence of DLA class II risk haplotypes for SLO, suggesting that the variants may reflect DLA class II haplotype association with disease or vice versa. Strong linkage disequilibrium in the region precluded the ability to isolate and assess the individual or combined effect of variants on disease development. Nonetheless, all were predictive of risk for SLO and, with judicious assessment, their application in selective breeding may prove useful to reduce the incidence of SLO in the breed.

Background The individual, together with its environment, has been reported as the main force driving composition and structure of skin microbiota in healthy dogs. Therefore, one of the major concerns when analyzing canine skin microbiota is the likely influence of the environment. Despite the dense fur covering, certain skin diseases exhibit differential prevalence among skin sites, dog breeds, and individuals. Results We have characterized the normal variability of dog skin microbiota in a well-controlled cohort of a large number of Golden-Labrador Retriever crossed dogs (N = 35) with similar ages, related genetic background, and a shared environment. We found that the individual drives the skin microbiota composition and structure followed by the skin site. The main bacterial classes inhabiting dog skin in this cohort are Gammaproteobacteria and Bacilli. We also detected bacteria associated to the environment on different dog skin sites that could be reflecting the different degrees of exposure of each skin site and each dog. Network analyses elucidated bacterial interactions within and between skin sites, especially in the chin, abdomen, axilla, and perianal region, with the highly shared interactions probably representing an anatomical, behavioral, or environmental component. When analyzing each skin site independently to assess host-specific factors, we found that temporality (season of birth and time spent in the kennel) affected all the skin sites and specially the inner pinna. The most abundant taxon driving this difference was Sphingomonas. We also found taxonomic differences among male and female dogs on the abdomen, axilla, and back. Conclusions We observed a large inter-individual variability and differences among skin sites. Host-specific variables, such as temporality or sex, were also shaping skin microbiota of healthy dogs, even in an environmental homogenous cohort. Electronic supplementary material The online version of this article (10.1186/s40168-017-0355-6) contains supplementary material, which is available to authorized users.

Symmetrical lupoid onychodystrophy (SLO) is characterized by inflammation of the nail bed and nail sloughing that causes affected dogs considerable pain. Disease etiology remains unclear, although an autoimmune component is suspected. A genome-wide association study on Bearded Collies revealed regions of association on canine chromosomes (CFA) 12 and 17. The large region of association on CFA12 likely consists of two smaller linked regions, both of which are also linked to the dog leukocyte antigen (DLA) class II genes. Dogs homozygous for the alternate allele at the top CFA12 SNP also carried two DLA class II risk haplotypes for SLO, and this locus explained most of the increased risk for disease seen throughout the CFA12 region of association. A stronger peak was seen on CFA17 when analysis was done solely on dogs that carried DLA class II risk haplotypes for SLO. The majority of SLO dogs carried a homozygous alternate genotype on CFA12 and at least one CFA17 risk haplotype. Our findings offer progress toward uncovering the genetic basis of SLO. While the contribution of the CFA17 region remains unclear, both CFA12 and CFA17 regions are significantly associated with SLO disease expression in the Bearded Collie and contain potential candidate genes for this disease.

Author(s): Cai, Stephen V; Famula, Thomas R; Oberbauer, Anita M; Hess, Rebecka S | Abstract: BackgroundHeritability and mode of inheritance of spontaneous diabetes mellitus (DM) in American Eskimo Dogs (AED) are unknown.ObjectiveInvestigate the heritability and mode of inheritance of DM in AED.AnimalsAn extended family of AED including 71 AED without DM, 47 AED with an unknown phenotype, and 38 AED with spontaneous DM.MethodsRetrospective evaluation of inheritance. A logistic regression model was formulated to evaluate the heritability of DM, including effects of sex and neuter status. Subsequently, complex segregation analysis was employed to investigate the inheritance pattern of DM in AED. Six plausible models were considered, and the Akaike Information Criterion was used to determine the best of the biologically feasible models of inheritance of DM in AED.ResultsHeritability of DM in AED is estimated at 0.62 (95% posterior interval 0.01-0.99). Predicted DM probabilities for neutered females (NF), intact females (IF), neutered males (NM), and intact males (IM) were 0.76, 0.11, 0.63, and 0.12, respectively. There was no overlap between the 95% posterior intervals of disease probabilities in NF and IF or in NF and IM. Complex segregation analysis suggested that the mode of inheritance of DM in AED is polygenic, with no evidence for a single gene of large effect.Conclusions and clinical importanceThe estimated heritability of DM in AED is high but has low precision. Diabetes mellitus transmission in AED appears to follow a polygenic inheritance. Breeders could successfully implement a breeding program to decrease the incidence of DM in AED.

Background Primary hypoadrenocorticism (Addison’s disease, AD) and symmetrical lupoid onychodystrophy (SLO) are two clinical conditions with an autoimmune etiology that occur in multiple dog breeds. In man, autoimmunity is associated with polymorphisms in immune-related genes that result in a reduced threshold for, or defective regulation of, T cell activation. The major histocompatibility complex (MHC) class II genes encode molecules that participate in these functions, and polymorphisms within these genes have been associated with autoimmune conditions in dogs and humans. Bearded collies have a relatively high prevalence of autoimmune diseases, particularly AD and SLO. Our study assessed the relationship between particular MHC (dog leukocyte antigen, DLA) class II haplotypes and the two autoimmune diseases most common in this breed. Moreover, five unrelated breeds at increased risk for AD were studied for comparative purposes and analyzed in the context of extant literature. Results A single DLA class II three-locus haplotype, determined by sequence-based typing, was associated with increased risk for AD (DLA-DRB1*009:01/DQA1*001:01/DQB1*008:02) in bearded collies. Comparative analysis with the five additional breeds showed limited allele sharing, with DQA1*001:01 and DQB1*002:01 being the only alleles observed in all breeds. A distinct three-locus risk haplotype (DLA-DRB1*001:01/DQA1*001:01/DQB1*002:01) was associated with AD in the West Highland white terrier and Leonberger. Two different risk haplotypes were associated with increased risk for SLO in the bearded collie (DLA-DRB1*018:01/DQA1*001:01/DQB1*002:01 and DLA-DRB1*018:01/DQA1*001:01/ DQB1*008:02). Conclusion Two-locus DQ haplotypes composed of DLA-DQA1*001:01 in association with DLA-DQB1*002:01 or DLA-DQB1*008:02 make up the four risk haplotypes identified in the present study and are also found in other risk haplotypes previously associated with diabetes mellitus and hypothyroidism across different dog breeds. Our findings build upon previously published data to suggest that this two-locus (DQ) model serves as a good indicator for susceptibility to multiple organ-specific autoimmune diseases in the canine population. However, it is also clear that additional loci are necessary for actual disease expression. Investigation of affected and unaffected dogs carrying these predisposing DQ haplotype signatures may allow for the identification of those additional genetic components that determine autoimmune disease expression and organ specificity. Electronic supplementary material The online version of this article (10.1186/s40575-019-0070-7) contains supplementary material, which is available to authorized users.

Canine elbow dysplasia is a significant health issue affecting many breeds. Unfortunately, treatments remain relatively limited, so control of this disease often falls to selectively breeding for dogs with normal elbows. The objectives of this study were to evaluate the heritability of left-sided vs. right-sided elbow dysplasia, and to assess potential differential sire and the dam influence on offspring elbow status. In a retrospective study, elbow data from 130,117 dogs over 2 years old representing 17 breeds were obtained from the database of the Orthopedic Foundation for Animals and included in the study. Heritability estimates for unilateral elbow dysplasia varied between breeds (ranging from 0.01 to 0.36) and were similar between the left and right elbows. The estimated genetic correlation between disease in the left and right elbow ~1 in the majority of breeds, with the exception of the hybrids, Australian Shepherds, and the Australian Cattle Dogs, likely due to low numbers of affected individuals. The sire and dam had equal impact on the offspring's elbow status. Furthermore, there was no increased risk for the sire or dam to pass on the same unilaterality of their elbow dysplasia to their offspring. However, the overall risk of elbow dysplasia in the offspring did increase when one or both parents were affected, though this also varied based on breed. Understanding of the impact that the sire and dam have on the offspring and of the overall heritability of both bilateral and unilateral elbow dysplasia is important in guiding breeding decisions to reduce the incidence in future generations of dogs.

Canine hip dysplasia (CHD) and elbow dysplasia (ED) impact the health and welfare of all dogs. The first formally organized assessment scheme to improve canine health centered on reducing the prevalence of these orthopedic disorders. Phenotypic screening of joint conformation remains the currently available strategy for breeders to make selection decisions. The present study evaluated the efficacy of employing phenotypic selection on breed improvement of hips and elbows using the Orthopedic Foundation for Animals complete database spanning the 1970-2015 time period. Sixty breeds having more than 1000 unique hip evaluations and 500 elbow evaluations (1,056,852 and 275,129 hip and elbow records, respectively) were interrogated to derive phenotypic improvement, sex and age at time of assessment effects, correlation between the two joints, heritability estimates, estimated breeding values (EBV), and effectiveness of maternal/paternal selection. The data demonstrated that there has been overall improvement in hip and elbow conformation with a reduction in EBV for disease liability, although the breeds differed in the magnitude of the response to selection. Heritabilities also differed substantially across the breeds as did the correlation of the joints; in the absence of a universal association of these differences with breed size, popularity, or participation in screening, it appears that the breeds themselves vary in genetic control. There was subtle, though again breed specific, impact of sex and older ages on CHD and ED. There was greater paternal impact on a reduction of CHD. In the absence of direct genetic tests for either of these two diseases, phenotypic selection has proven to be effective. Furthermore, the data underscore that selection schemes must be breed specific and that it is likely the genetic profiles will be unique across the breeds for these two conditions. Despite the advances achieved with phenotypic selection, incorporation of EBVs into selection schemes should accelerate advances in hip and elbow improvement.

Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes-some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath.

Background Gonadectomy, or neutering, is a very common surgery for dogs having many positive effects on behavior, health, and longevity. There are also certain risks associated with neutering including the development of orthopedic conditions, cognitive decline, and a predisposition to some neoplasias. This study was designed specifically to identify if a correlation exists between neuter status and inherited conditions in a large aggregate cohort of dogs representing many different breeds. Results Neutered dogs were at less risk for early and congenital conditions (aortic stenosis, early onset cataracts, mitral valve disease, patent ductus arteriosus, portosystemic shunt, and ventricular septal defect) than intact dogs. Neutering was also associated with reduced risk of dilated cardiomyopathy and gastric dilatation volvulus in males. Neutering was significantly associated with an increased risk for males and females for cancers (hemangiosarcoma, hyperadrenocorticism, lymphoma, mast cell tumor, and osteosarcoma), ruptured anterior cruciate ligament and epilepsy. Intervertebral disk disease was associated with increased risk in females only. For elbow dysplasia, hip dysplasia, lens luxation, and patellar luxation neutering had no significant effect on the risk for those conditions. Neutering was associated with a reduced risk of vehicular injury, a condition chosen as a control. Conclusions In this retrospective study, several conditions showed an increased risk associated with neutering whereas other conditions were less likely to be expressed in neutered dogs. The complexity of the interactions between neutering and inherited conditions underscores the need for reflective consultation between the client and the clinician when considering neutering. The convenience and advantages of neutering dogs that will not be included in a breeding program must be weighed against possible risk associated with neutering. Electronic supplementary material The online version of this article (doi:10.1186/s40575-017-0044-6) contains supplementary material, which is available to authorized users.

There is considerable interest in the genetics of wolves (Canis lupus) because of their close relationship to domestic dogs (C. familiaris) and the need for informed conservation and management. This includes wolf populations in Southeast Alaska for which we determined genotypes of 305 wolves at 173 662 single nucleotide polymorphism (SNP) loci. After removal of invariant and linked SNP, 123 801 SNP were used to quantify genetic differentiation of wolves in Southeast Alaska and wolves, coyotes (C. latrans ), and dogs from other areas in North America. There is differentiation of SNP allele frequencies between the species (wolves, coyotes, and dogs), although differentiation is relatively low between some wolf and coyote populations. There are varying levels of differentiation among populations of wolves, including low differentiation of wolves in interior Alaska, British Columbia, and the northern US Rocky Mountains. There is considerable differentiation of SNP allele frequencies of wolves in Southeast Alaska from wolves in other areas. However, wolves in Southeast Alaska are not a genetically homogeneous group and there are comparable levels of genetic differentiation among areas within Southeast Alaska and between Southeast Alaska and other geographic areas. SNP variation and other genetic data are discussed regarding taxonomy and management.

Objective—To determine whether vaccination with a monovalent vaccine against Leptospira borgpetersenii serovar Hardjo strain hardjobovis would improve reproductive efficiency in Holstein cattle in a commercial dairy setting. Design—Randomized controlled trial. Animals—1,894 Holstein cows and heifers from a Central California dairy. Procedures—Cattle were assigned to undergo SC administration of a monovalent vaccine against Leptospira borgpetersenii serovar Hardjo strain hardjobovis (n = 986) or a placebo (lactated Ringer's solution; 908). At the end of their lactation period, cows received 2 doses of the vaccine or placebo, 28 to 35 days apart, with the initial dose administered in conjunction with oxytetracycline. Heifers received the same treatments, with the second dose administered at least 2 weeks before their entrance into the heifer breeding pen. Urine and blood samples were collected from randomly selected cattle immediately before and 1 year after the trial began and submitted for fluorescent antibody and microscopic agglutination testing to identify any infecting Leptospira serovar. Results—The initial herd prevalence of active infection with strain hardjobovis was 13% (6/46 tested cattle), followed by 15% (6/40) 1 year after the trial began. The odds of heifers conceiving over the period at risk for conception, regardless of vaccination, was approximately 2.8 times as high as for primiparous and pluriparous cows. Survival analysis of days from parturition to conception revealed that the vaccine protocol had no effect on the probability of conception between the vaccinated and control groups. The vaccine protocol had no impact on pregnancy loss. Conclusions and Clinical Relevance—The evaluated vaccination protocol against Leptospira strain hardjobovis was not effective in improving reproductive efficiency in commercial Holstein dairy cows or in decreasing urine shedding of leptospires.

Lameness and hoof health affect dairy cows as an animal welfare issue, in decreased milk production, and in premature culling. Selection schemes for dairy cattle focus on sire contribution to milk production, with little consideration of the cow's physical structure or disease probability. On 3 commercial California dairies, 6 phenotypic binary hoof traits that contribute to lameness were recorded: white line disease, sole ulcer, other claw horn lesions, foot rot (interdigital phlegmon), foot warts (digital dermatitis), and other lesions. Monthly lactation records were collected from December 2006 to April 2009 with weekly observations of hoof lesions for lame and dry cows. In addition to hoof lesion information, data on cows (n=5,043) included parentage, birth date, freshening date, lactation number, and date of lameness diagnosis. The prevalence of hoof lesions ranged from a low of 2.2% (foot rot) to a high of 17.1% (foot warts). The farm environment increased the odds ratio depending upon the lesion. Lameness was more common in early lactation and as lactation number increased. Using a threshold model, heritabilities and repeatabilities were estimated for each binary trait. The heritability for risk varied by lesion, with the higher estimates being 0.40 (95% confidence interval: 0.20-0.67) for digital dermatitis and 0.30 (95% confidence interval: 0.08-0.63) for sole ulcer. Including terms to account for cow productivity on either a 305-d mature-equivalent basis or a per-lactation basis had minimal effect on the heritability estimates, suggesting that selection for hoof health is not correlated with response to selection for greater milk production and that improvement could be made for both traits. The genetic component lends support for further genetic studies to identify loci contributing to some of the lesion phenotypes such as foot warts or sole ulcers, 2 of the top 3 causes of lameness in dairy cattle.

Background Valued for trainability in diverse tasks, dogs are the primary service animal used to assist individuals with disabilities. Despite their utility, many people in need of service dogs are sensitive to the primary dog allergen, Can f 1, encoded by the Lipocalin 1 gene (LCN1). Several organizations specifically breed service dogs to meet special needs and would like to reduce allergenic potential if possible. In this study, we evaluated the expression of Can f 1 protein and the inherent variability of LCN1 in two breeds used extensively as service dogs. Saliva samples from equal numbers of male and female Labrador retrievers (n = 12), golden retrievers (n = 12), and Labrador-golden crosses (n = 12) were collected 1 h after the morning meal. Can f 1 protein concentrations in the saliva were measured by ELISA, and the LCN1 5′ and 3′ UTRs and exons sequenced. Results There was no sex effect (p > 0.2) nor time-of-day effect; however, Can f 1 protein levels varied by breed with Labrador retrievers being lower than golden retrievers (3.18 ± 0.51 and 5.35 ± 0.52 μg/ml, respectively, p

In a transgenic growth hormone (GH) mouse model, highly elevated GH increases overall growth and decreases adipose depots while low or moderate circulating GH enhances adipose deposition with differential effects on body growth. Using this model, the effects of low, moderate, and high chronic GH on fatty acid composition were determined for adipose and hepatic tissue and the metabolites of 20:4n-6 (arachidonic acid) were characterized to identify metabolic targets of action of elevated GH. The products of Δ-9 desaturase in hepatic, but not adipose, tissue were reduced in response to elevated GH. Proportional to the level of circulating GH, the products of Δ-5 and Δ-6 were increased in both adipose and hepatic tissue for the omega-6 lipids (e.g., 20:4n-6), while only the hepatic tissues showed an increase for omega-3 lipids (e.g., 22:6n-3). The eicosanoids, PGE2 and 12-HETE, were elevated with high GH but circulating thromboxane was not. Hepatic PTGS1 and 2 (COX1 and COX 2), SOD1, and FADS2 (Δ-6 desaturase) mRNAs were increased with elevated GH while FAS mRNA was reduced; SCD1 (ste-aroyl-coenzyme A desaturase) and SCD2 mRNA did not significantly differ. The present study showed that GH influences the net flux through various aspects of lipid metabolism and especially the desaturase metabolic processes. The combination of altered metabolism and tissue specificity suggest that the regulation of membrane composition and its effects on signaling pathways, including the production and actions of eicosanoids, can be mediated by the GH regulatory axis.

Unsaturated omega-3 fatty acids, especially docosahexaenoic acid (DHA), when fed to dogs improves cognitive and neurological development. Supplementation with omega-3 fatty acids such as DHA and eicosapentaenoic acid (EPA) has also been associated with lipid peroxidation, which in turn has been implicated in reduced body weight and altered bone formation. To assess the impact of omega-3 fatty acid supplementation on skeletal growth, diets containing three levels of DHA and EPA (0.01 and 0.01%, 0.14 and 0.12%, and 0.21 and 0.18%, respectively) were fed to bitches during gestation and lactation with puppies also supplemented through weaning. Thus, the subjects studied were the puppies supplemented with DHA and EPA through gestation and early postnatal life. The hip joint conformation of the puppies (n = 676) was recorded at adulthood using two radiographic, non-invasive evaluations. In this population, females had higher hip distraction indices (DI) than males. Males from the lower two levels of DHA and EPA supplementation had significantly smaller hip DI than all females and males from the highest DHA and EPA supplementation. In contrast, there were no diet effects on anatomical indicators of hip joint conformation and no visible arthritic changes. These data suggest that dietary supplementation of DHA and EPA during gestation and the perinatal period to weaning does not adversely influence hip joint formation of dogs.

Raising a heifer calf to reproductive age represents an enormous cost to the producer. Poor neonatal growth exacerbates the costs incurred for rearing, and use of blood variables that may be associated with poorly growing calves may offer predictive value for growth and performance. Thus, the principal objective of the present study was to describe changes in serum IGF-I, zinc, and copper from birth to 90 d in Holstein calves, while accounting for sex and twin status, in poorly growing calves and calves growing well. A second objective was to test the hypothesis that an association exists between these serum variables and morphometric indicators of growth. Measurements of BW, length, and height were recorded at birth and at 30, 60, and 90 d of age. Jugular blood (12 mL) was collected from each calf on d 1 to determine serum total protein, serum IgG, packed cell volume, serum zinc, serum copper, serum IGF-I, and CD18 genotype for bovine leukocyte adhesion deficiency; serum zinc, serum copper, and serum IGF-I (predictor variables) were also determined for each calf on d 2 through 10 and on d 30, 60, and 90. Stepwise multiple regression and logistic regression analyses were used to examine the relationships between the predictor variables and the dependent variables (BW, height, and length at d 30, 60, and 90 of life). Birth weight, sex, serum IGF-I (at all ages), serum copper, and the serum copper-to-zinc ratio were associated, to varying degrees, with the dependent growth variables. Birth weight was consistently the dominant predictor. In conclusion, these results suggest that lighter birth weight, reduced serum IGF-I, and inflammation may be important causes of poor growth in neonatal Holstein dairy calves.

Bisphosphonates decrease chondrocyte turnover at the growth plate and impact bone growth. Likewise vascular endothelial growth factor (VEGF) plays an important role in endochondral bone elongation by influencing chondrocyte turnover at the growth plate. To investigate whether the action of bisphosphonate on the growth plate works through VEGF, VEGF protein expression and isoform transcription in endochondral chondrocytes isolated from growing mice and treated with a clinically used bisphosphonate, alendronate, were assessed. Alendronate at 10µM and 100µM concentrations decreased secreted VEGF protein expression but not cell associated protein. Bisphosphonates are known to inhibit the mevalonate intracellular signaling pathway used by VEGF. Addition of the mevalonate pathway intermediates farnesol (FOH) and geranylgeraniol (GGOH) interacted with the low concentration of alendronate to further decrease secreted VEGF protein whereas FOH partially restored VEGF protein secretion when combined with the high alendronate. Similar to the protein data, the addition of alendronate decreased VEGF mRNA isoforms. VEGF mRNA levels were rescued by the GGOH mevalonate pathway intermediate at the low alendronate dose whereas neither intermediate consistently restored the VEGF mRNA levels at the high alendronate dose. Thus, the bisphophonate alendronate impairs growth plate chondrocyte turnover by down-regulating the secreted forms of VEGF mRNA and protein by inhibiting the mevalonate pathway.

Osteogenesis imperfecta (OI) is a heritable disease, which results from an abnormal amount or structure of Type I collagen. Bisphosphonates, a class of synthetic antiresorptive drugs, used in osteoporosis management, are also used to decrease fracture incidence and improve quality of life in children with OI. In this study, we used the oim mouse to test the hypotheses that pamidronate treatment during active growth (1) produces larger, stronger, stiffer long bone diaphyses without altering bone material properties, and (2) negatively impacts longitudinal bone growth. Our results indicate that femoral cross-sectional moment of inertia in the distal metaphysis tended to increase with pamidronate treatment and that the treated bones are thicker and structurally stiffer, but shorter than their control-dose counterparts.

Objective—To characterize heritability and mode of inheritance of cataracts and primary lens luxation in Jack Russell Terriers. Animals—872 Jack Russell Terriers from which buccal epithelial cells were collected and phenotypes for cataracts and lens luxation were determined and an additional 1,898 Jack Russell Terriers without phenotypic information used to complete pedigree relationships and that were included in the analyses. Procedures—Narrow-sense heritabilities and genetic correlation for cataracts and lens luxation were modeled by use of threshold analysis, whereas complex segregation analysis was used to characterize mode of inheritance. For the analyses, dogs < 6 years old, unless confirmed as having cataracts or lens luxation, were classified as an unknown phenotype. The possible involvement of an HSF4 mutation in cataracts was determined by DNA sequencing. Results—Cataracts and primary lens luxation were highly heritable and genetically correlated, and neither was controlled by a single gene. Cataracts were not associated with an HSF4 mutation. Conclusions and Clinical Relevance—Analysis of the data indicated that concerted selection against both cataracts and primary lens luxation when choosing breeding animals can be used to improve ocular health in Jack Russell Terriers.

Vascular endothelial growth factor (VEGF) is implicated as a key angiogenic factor in the development of endochondral long bone. Several studies have evaluated the role of VEGF in prenatal endochondral bone development, but few have evaluated VEGF postnatally. Growth plates from mice at postnatal ages 14 (P14), 35 (P35), 49 (P49), and 77 (P77) days were examined for differential expression of the primary VEGF-A mRNA isoforms: VEGF 120, VEGF 164, and VEGF 188. VEGF 120 isoform expression was stable across all ages, whereas VEGF 164 had significantly less expression at P35 and P49 and VEGF l88 expression increased with increasing age. The proportion of transcript isoforms expressed at a given age also changed with VEGF 120 being expressed more highly at P35 and P49 than the other two isoforms. Changes in VEGF mRNA isoforms across cell types within the growth plate were assessed by Percoll fractionation of growth plate cells at age P28. Cells of the proliferative and early hypertrophic regions had significantly higher total VEGF mRNA expression relative to the resting and late hypertrophic regions. VEGF protein expression assessed by immunohistochemistry showed variable expression patterns with increasing postnatal age. In contrast, FLK-1 (VEGF Receptor-2) expression was restricted to the hypertrophic region. These results indicate that VEGF continues to play a significant role in endochondral bone development throughout the entire growth phase of postnatal bone development.

Background Idiopathic epilepsy is a common neurological disease in human and domestic dogs but relatively few risk genes have been identified to date. The seizure characteristics, including focal and generalised seizures, are similar between the two species, with gene discovery facilitated by the reduced genetic heterogeneity of purebred dogs. We have recently identified a risk locus for idiopathic epilepsy in the Belgian Shepherd breed on a 4.4 megabase region on CFA37. Results We have expanded a previous study replicating the association with a combined analysis of 157 cases and 179 controls in three additional breeds: Schipperke, Finnish Spitz and Beagle (pc = 2.9e–07, pGWAS = 1.74E-02). A targeted resequencing of the 4.4 megabase region in twelve Belgian Shepherd cases and twelve controls with opposite haplotypes identified 37 case-specific variants within the ADAM23 gene. Twenty-seven variants were validated in 285 cases and 355 controls from four breeds, resulting in a strong replication of the ADAM23 locus (praw = 2.76e–15) and the identification of a common 28 kb-risk haplotype in all four breeds. Risk haplotype was present in frequencies of 0.49–0.7 in the breeds, suggesting that ADAM23 is a low penetrance risk gene for canine epilepsy. Conclusions These results implicate ADAM23 in common canine idiopathic epilepsy, although the causative variant remains yet to be identified. ADAM23 plays a role in synaptic transmission and interacts with known epilepsy genes, LGI1 and LGI2, and should be considered as a candidate gene for human epilepsies. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1651-9) contains supplementary material, which is available to authorized users.