Congenital idiopathic megaesophagus in the German shepherd dog is a sex-differentiated trait and is associated with an intronic variable number tandem repeat in Melanin-Concentrating Hormone Receptor 2.

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 necessitate euthanasia. The German shepherd dog (GSD) has the highest disease incidence, indicative of a genetic predisposition. Here, we discover that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage. A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility. Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM. We describe herein the first genetic factors identified in CIM: sex and a major locus on chromosome 12, which together predict disease state in the GSD with greater than 75% accuracy.

Variants in FtsJ RNA 2'-O-Methyltransferase 3 and Growth Hormone 1 are associated with small body size and a dental anomaly in dogs.

Domesticated dogs show unparalleled diversity in body size across breeds, but within breeds variation is limited by selective breeding. Many heritable diseases of dogs are found among breeds of similar sizes, suggesting that as in humans, alleles governing growth have pleiotropic effects. Here, we conducted independent genome-wide association studies in the small Shetland Sheepdog breed and discovered a locus on chromosome 9 that is associated with a dental abnormality called maxillary canine-tooth mesioversion (MCM) (P = 1.53 × 10-7) as well as two body size traits: height (P = 1.67 × 10-5) and weight (P = 1.16 × 10-7). Using whole-genome resequencing data, we identified variants in two proximal genes: FTSJ3, encoding an RNA methyltransferase, and GH1, encoding growth hormone. A substitution in FTSJ3 and a splice donor insertion in GH1 are strongly associated with MCM and reduced body size in Shetland Sheepdogs. We demonstrated in vitro that the GH1 variant leads to exon 3 skipping, predicting a mutant protein known to cause human pituitary dwarfism. Statistical modeling, however, indicates that the FTSJ3 variant is the stronger predictor of MCM and that each derived allele reduces body size by about 1 inch and 5 pounds. In a survey of 224 breeds, both FTSJ3 and GH1 variants are frequent among very small "toy" breeds and absent from larger breeds. Our findings indicate that a chromosome 9 locus harboring tightly linked variants in FTSJ3 and GH1 reduces growth in the Shetland Sheepdog and toy breed dogs and confers risk for MCM through vertical pleiotropy.

Genetic characterization of Addison's disease in Bearded Collies.

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.

Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci.

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 histocompatibility complex (MHC) (DLA-DRB1*002:01/-DQA1*009:01/-DQB1*001:01), particularly in homozygosity (P-val = 0.0001). However, the high incidence of the haplotype among healthy dogs indicated that additional genetic risk factors are likely involved in disease progression. We conducted genome-wide association studies in two modern breeds having common ancestry and detected strong associations with novel loci on canine chromosomes 10 (P-val = 2.3X10-12) and 31 (P-val = 3.95X10-8). Through whole genome resequencing, we identified primary candidate polymorphisms in conserved regions of PAN2 (encoding p.Arg492Cys) and MAP3K7CL (c.383_392ACTCCACAAA>GACT) on chromosomes 10 and 31, respectively. Analyses of these polymorphisms and the MHC haplotypes revealed that nine of 27 genotypic combinations confer high or moderate probability of disease and explain 93% of cases studied. The pattern of disease risk across PAN2 and MAP3K7CL genotypes provided clear evidence for a significant epistatic foundation for this disease, a risk further impacted by MHC haplotypes. We also observed a genotype-phenotype correlation wherein an earlier age of onset is correlated with an increased number of risk alleles at PAN2 and MAP3K7CL. High frequencies of multiple genetic risk factors are unique to affected breeds and likely arose coincident with artificial selection for desirable phenotypes. Described herein is the first three-locus association with a complex canine disease and two novel loci that provide targets for exploration in JDM and related immunological dysfunction.

Application of a Bayesian ordinal animal model for the estimation of breeding values for the resistance to Monilinia fruticola (G.Winter) Honey in progenies of peach [Prunus persica (L.) Batsch].

Fruit brown rot caused by Monilinia spp. is the most important fungal disease of stone fruits worldwide. Several phenotyping protocols to accurately characterize and evaluate brown rot infection have been proposed; however, the outcomes from those studies have not led to consistent advances in resistance breeding programs. Breeding for disease resistance is one of the most challenging objectives for crop improvement because disease expression is tetrahedral: it is simultaneously influenced by agent, host, environment, and human management. The present study presents a strategy based on Bayesian inference to analyze a peach breeding progeny for resistance to brown rot, evaluated using a polytomous ordinal scale. A pedigree containing two sources of resistance, one from peach and the other from almond, several commercial cultivars, and two segregating populations were analyzed to estimate the narrow-sense heritability (h2 ) and breeding values (EBVs) for brown rot resistance in progenies. Results show promise for genetic improvement of disease resistance and other traits characterized by strong environmental interactions.

Gonadectomy effects on the risk of immune disorders in the dog: a retrospective study.

BACKGROUND: Gonadectomy is one of the most common procedures performed on dogs in the United States. Neutering has been shown to reduce the risk for some diseases although recent reports suggest increased prevalence for structural disorders and some neoplasias. The relation between neuter status and autoimmune diseases has not been explored. This study evaluated the prevalence and risk of atopic dermatitis (ATOP), autoimmune hemolytic anemia (AIHA), canine myasthenia gravis (CMG), colitis (COL), hypoadrenocorticism (ADD), hypothyroidism (HYPO), immune-mediated polyarthritis (IMPA), immune-mediated thrombocytopenia (ITP), inflammatory bowel disease (IBD), lupus erythematosus (LUP), and pemphigus complex (PEMC), for intact females, intact males, neutered females, and neutered males. Pyometra (PYO) was evaluated as a control condition. RESULTS: Patient records (90,090) from the William R. Pritchard Veterinary Medical Teaching Hospital at the University of California, Davis from 1995 to 2010 were analyzed in order to determine the risk of immune-mediated disease relative to neuter status in dogs. Neutered dogs had a significantly greater risk of ATOP, AIHA, ADD, HYPO, ITP, and IBD than intact dogs with neutered females being at greater risk than neutered males for all but AIHA and ADD. Neutered females, but not males, had a significantly greater risk of LUP than intact females. Pyometra was a greater risk for intact females. CONCLUSIONS: The data underscore the importance of sex steroids on immune function emphasizing a role of these hormones on tissue self-recognition. Neutering is critically important for population control, reduction of reproductive disorders, and offers convenience for owners. Despite these advantages, the analyses of the present study suggest that neutering is associated with increased risk for certain autoimmune disorders and underscore the need for owners to consult with their veterinary practitioner prior to neutering to evaluate possible benefits and risks associated with such a procedure.

Overlapping mouse subcongenic strains successfully separate two linked body fat QTL on distal MMU 2.

BACKGROUND: Mouse chromosome 2 is linked to growth and body fat phenotypes in many mouse crosses. With the goal to identify the underlying genes regulating growth and body fat on mouse chromosome 2, we developed five overlapping subcongenic strains that contained CAST/EiJ donor regions in a C57BL/6J (hg/hg) background (hg is a spontaneous deletion of 500 Kb on mouse chromosome 10). To fine map QTL on distal mouse chromosome 2 a total of 1,712 F2 mice from the five subcongenic strains, plus 278 F2 mice from the HG2D founder congenic strain were phenotyped and analyzed. Interval mapping (IM) and composite IM (CIM) were performed on body weight and body fat traits on a combination of SNP and microsatellite markers, which generated a high-density genotyping panel. RESULTS: Phenotypic analysis and interval mapping of total fat mass identified two QTL on distal mouse chromosome 2. One QTL between 150 and 161 Mb, Fatq2a, and the second between 173.3 and 175.6 Mb, Fatq2b. The two QTL reside in different congenic strains with significant total fat differences between homozygous cast/cast and b6/b6 littermates. Both of these QTL were previously identified only as a single QTL affecting body fat, Fatq2. Furthermore, through a novel approach referred here as replicated CIM, Fatq2b was mapped to the Gnas imprinted locus. CONCLUSIONS: The integration of subcongenic strains, high-density genotyping, and CIM succesfully partitioned two previously linked QTL 20 Mb apart, and the strongest QTL, Fatq2b, was fine mapped to a ~2.3 Mb region interval encompassing the Gnas imprinted locus.

Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH.

Equine Cerebellar Abiotrophy (CA) is a neurological disease found in Arabian horses. CA is characterized by post-natal degeneration of the Purkinje cells of the cerebellum. Signs of CA include ataxia, head tremors, and a lack of balance equilibrium. We have discovered a linkage of the CA phenotype to a microsatellite marker on ECA2 and identified a region of conserved homozygosity spanning approximately 142 kb. Complete sequencing of the four genes in this region identified one SNP found only in Arabian horses, located in exon 4 of TOE1 and approximately 1200 base pairs upstream of MUTYH, adjacent to a possible binding site for the transcription factor GATA2. qPCR analysis of cDNA from the cerebella of affected and unaffected horses suggested that MUTYH expression is down-regulated in affected horses. This SNP may therefore have a function effect on TOE1, or a regulatory effect on MUTYH by negatively affecting the binding affinity of GATA2.

Validation of a Chromosome 14 Risk Haplotype for Idiopathic Epilepsy in the Belgian Shepherd Dog Found to Be Associated with an Insertion in the RAPGEF5 Gene.

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 (p < 0.003) with reduced risk in the new cohort. However, the CFA14 ACTG risk was statistically significant when the new and previous cohort data were combined. The frequency of the ACTG haplotype was four-fold higher in BS dogs than in other breeds. Whole genome sequence analysis revealed that a 3-base pair predicted disruptive insertion in the RAPGEF5 gene, which is adjacent to the CFA14 risk haplotype. RAPGEF5 is involved in the Wnt-ß-catenin signaling pathway that is crucial for normal brain function. Although this risk variant does not fully predict the likelihood of a BS developing IE, the association with a variant in a candidate gene may provide insight into the genetic control of canine IE.

Unique Transcriptomic Changes Underlie Hormonal Interactions During Mammary Histomorphogenesis in Female Pigs.

Successful lactation and the risk for developing breast cancer depend on growth and differentiation of the mammary gland (MG) epithelium that is regulated by ovarian steroids (17ß-estradiol [E] and progesterone [P]) and pituitary-derived prolactin (PRL). Given that the MG of pigs share histomorphogenic features present in the normal human breast, we sought to define the transcriptional responses within the MG of pigs following exposure to all combinations of these hormones. Hormone-ablated female pigs were administered combinations of E, medroxyprogesterone 17-acetate (source of P), and either haloperidol (to induce PRL) or 2-bromo-α-ergocryptine. We subsequently monitored phenotypic changes in the MG including mitosis, receptors for E and P (ESR1 and PGR), level of phosphorylated STAT5 (pSTAT5), and the frequency of terminal ductal lobular unit (TDLU) subtypes; these changes were then associated with all transcriptomic changes. Estrogen altered the expression of approximately 20% of all genes that were mostly associated with mitosis, whereas PRL stimulated elements of fatty acid metabolism and an inflammatory response. Several outcomes, including increased pSTAT5, highlighted the ability of E to enhance PRL action. Regression of transcriptomic changes against several MG phenotypes revealed 1669 genes correlated with proliferation, among which 29 were E inducible. Additional gene expression signatures were associated with TDLU formation and the frequency of ESR1 or PGR. These data provide a link between the hormone-regulated genome and phenome of the MG in a species having a complex histoarchitecture like that in the human breast, and highlight an underexplored synergy between the actions of E and PRL during MG development.

Characteristics of compulsive tail chasing and associated risk factors in Bull Terriers.

OBJECTIVE: To evaluate and define the characteristics of tail chasing in Bull Terriers and explore the association between tail chasing and other behavioral and physical characteristics. DESIGN: Survey and case-control study. ANIMALS: 333 Bull Terriers (145 dogs with tail-chasing behavior and 188 unaffected dogs). PROCEDURES: Owners of Bull Terriers with tail-chasing behavior were surveyed regarding the age of onset, triggers, frequency, duration, interruptability, degree of disruption to the dogs' normal functioning and the owners' relationship with the dog, and associated medical and physical consequences. Associations of tail chasing with various behavioral and physical characteristics were examined by comparison of dogs with tail-chasing behavior with unaffected dogs. RESULTS: Phenotypic and developmental descriptions of tail chasing in Bull Terriers were defined. Associations of tail chasing with sex, trance-like behavior, and episodic aggression were found. Males were at an 8% greater risk for the diagnosis of tail chasing than females. Phobias and owner-directed aggression did not significantly associate with tail chasing in the final log-linear model, but did have significant associations in earlier analyses that did not include the behaviors of episodic aggression and trance-like behavior. CONCLUSIONS AND CLINICAL RELEVANCE: In Bull Terriers with tail-chasing behavior, there was a slight increase in the susceptibility of males to develop tail-chasing behavior, compared with females. A close association of tail chasing with trance-like behavior and episodic aggression was identified.

Genome-Wide Association Studies Reveal Susceptibility Loci for Noninfectious Claw Lesions in Holstein Dairy Cattle.

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.

Pleiotropic Loci Associated With Foot Disorders and Common Periparturient Diseases in Holstein Cattle.

Lameness is an animal welfare issue that incurs substantial financial and environmental costs. This condition is commonly caused by digital dermatitis (DD), sole ulcers (SU), and white line disease (WLD). Susceptibility to these three foot disorders is due in part to genetics, indicating that genomic selection against these foot lesions can be used to reduce lameness prevalence. It is unclear whether selection against foot lesions will lead to increased susceptibility to other common diseases such as mastitis and metritis. Thus, the aim of this study was to determine the genetic correlation between causes of lameness and other common health disorders to identify loci contributing to the correlation. Genetic correlation estimates between SU and DD and between SU and WLD were significantly different from zero (p < 0.05), whereas estimates between DD and mastitis, DD and milk fever, and SU and metritis were suggestive (p < 0.1). All five of these genetic correlation estimates were positive. Two-trait genome-wide association studies (GWAS) for each of these five pairs of traits revealed common regions of association on BTA1 and BTA8 for pairs that included DD or SU as one of the traits, respectively. Other regions of association were unique to the pair of traits and not observed in GWAS for other pairs of traits. The positive genetic correlation estimates between foot disorders and other health disorders imply that selection against foot disorders may also decrease susceptibility to other health disorders. Linkage disequilibrium blocks defined around significant and suggestive SNPs from the two-trait GWAS included genes and QTL that were functionally relevant, supporting that these regions included pleiotropic loci.

Enhancing student scientific literacy through participation in citizen science focused on companion animal behavior.

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.

Early-emerging and highly heritable sensitivity to human communication in dogs.

Human cognition is believed to be unique in part because of early-emerging social skills for cooperative communication.1 Comparative studies show that at 2.5 years old, children reason about the physical world similarly to other great apes, yet already possess cognitive skills for cooperative communication far exceeding those in our closest primate relatives.2,3 A growing body of research indicates that domestic dogs exhibit functional similarities to human children in their sensitivity to cooperative-communicative acts. From early in development, dogs flexibly respond to diverse forms of cooperative gestures.4,5 Like human children, dogs are sensitive to ostensive signals marking gestures as communicative, as well as contextual factors needed for inferences about these communicative acts.6-8 However, key questions about potential biological bases for these abilities remain untested. To investigate their developmental and genetic origins, we tested 375 8-week-old dog puppies on a battery of social-cognitive measures. We hypothesized that if dogs' skills for cooperating with humans are biologically prepared, then they should emerge robustly in early development, not require extensive socialization or learning, and exhibit heritable variation. Puppies were highly skillful at using diverse human gestures, and we found no evidence that their performance required learning. Critically, over 40% of the variation in dogs' point-following abilities and attention to human faces was attributable to genetic factors. Our results suggest that these social skills in dogs emerge early in development and are under strong genetic control.

Genome-wide linkage scan for loci associated with epilepsy in Belgian shepherd dogs.

BACKGROUND: Idiopathic epilepsy in the Belgian shepherd dog is known to have a substantial genetic component. The objective of this study was to identify genomic regions associated with the expression of generalized seizures in the Belgian Tervuren and Sheepdog. RESULTS: DNA from 366 dogs, of which 74 were classified as epileptic, representing two extended families were subjected to a genome-wide linkage scan using 410 microsatellite markers yielding informative coverage averaging 5.95 +/- 0.21 Mb. Though previous studies based on pedigree analyses proposed a major gene of influence, the present study demonstrated the trait to be highly polygenic. Studies of complex disorders in humans indicate that a liberal composite evaluation of genetic linkage is needed to identify underlying quantitative trait loci (QTLs). Four chromosomes yielded tentative linkage based upon LOD scores in excess of 1.0. Possible QTLs within these regions were supported also by analyses of multipoint linkage, allele frequency, TDT, and transmission of haplotype blocks. CONCLUSIONS: Taken together the data tentatively indicate six QTLs, three on CFA 2, and one on each of CFA 6, 12, and 37, that support fine mapping for mutations associated with epilepsy in the Belgian shepherd. The study also underscores the complexity of genomic linkage studies for polygenic disorders.

Clinical, histologic, and bacteriologic findings in dairy cows with digital dermatitis (footwarts) one month after topical treatment with lincomycin hydrochloride or oxytetracycline hydrochloride.

OBJECTIVE: To compare the effectiveness of lincomycin and oxytetracycline for treatment of digital dermatitis (DD) in dairy cows through gross visual examination, histologic evaluation, and bacteriologic evaluation. DESIGN: Randomized controlled clinical trial. ANIMALS: 25 cows with DD lesions from a commercial Holstein dairy herd. PROCEDURES: Cows with DD lesions were randomly assigned to 1 of 3 groups: topical treatment with 10 g of lincomycin hydrochloride (n = 11), topical treatment with 10 g of oxytetracycline hydrochloride (11), and no treatment (3) on days 1 and 2 (d1). Biopsy specimens were obtained for histologic examination from DD lesions prior to treatment and 28 or 31 days (d30) after treatment for histologic examination. Cows were clinically examined on d1, days 12 or 14 (d14), and d30. RESULTS: No difference was evident in clinical responses to lincomycin and oxytetracycline, so data were pooled; at d30, 8 of 11 of lincomycin-treated lesions and 7 of 11 oxytetracycline-treated lesions appeared visually healed, respectively. Gross visual examination suggested 73% (16/22) of treated cows were healed at d14 and 68% (15/22) of treated cows were healed on d30. Of the 15 lesions that appeared healed on d30, 7 of 15 were classified histologically as active (ulceration and bacterial invasion; 2/15) or incipient (5/15). CONCLUSIONS AND CLINICAL RELEVANCE: Clinical responses to lincomycin and oxytetracycline did not differ. Agreement was good between gross visual and histologic assessments of DD lesions before treatment; agreement 1 month after treatment was variable. Histologic evaluation could not distinguish incomplete healing from lesion recurrence.

Heritability and complex segregation analysis of naturally-occurring diabetes in Australian Terrier Dogs.

The Australian Terrier breed is the breed at highest risk for naturally-occurring diabetes mellitus in the United States, where it is 32 times more likely to develop diabetes compared to mixed breed dogs. However, the heritability and mode of inheritance of spontaneous diabetes in Australian Terriers has not been reported. The aim of this study was therefore to investigate the heritability and mode of inheritance of diabetes in Australian Terriers. A cohort of related Australian Terriers including 383 Australian Terriers without diabetes, 86 Australian Terriers with spontaneous diabetes, and 14 Australian Terriers with an unknown phenotype, was analyzed. A logistic regression model including the effects of sex was formulated to evaluate the heritability of diabetes. The inheritance pattern of spontaneous diabetes in Australian Terriers was investigated by use of complex segregation analysis. Six possible inheritance models were studied, and the Akaike Information Criterion was used to determine the best model for diabetes inheritance in Australian Terriers, among the models deemed biologically feasible. Heritability of diabetes in Australian Terriers was estimated at 0.18 (95% confidence interval 0.0-0.67). There was no significant difference in the effect of males and females on disease outcome. Complex segregation analysis suggested that the mode of diabetes inheritance in Australian Terriers is polygenic, with no evidence for a large effect single gene influencing diabetes. It is concluded that in the population of Australian Terriers bred in the United States, a relatively small degree of genetic variation contributes to spontaneous diabetes. A genetic uniformity for diabetes-susceptible genes within the population of Australian Terriers bred in the Unites States could increase the risk of diabetes in this cohort. These findings hold promise for future genetic studies of canine diabetes focused on this particular breed.

Genome-Wide Association Studies Reveal Susceptibility Loci for Digital Dermatitis in Holstein Cattle.

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 ≥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.