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Lumbosacral stenosis in Labrador retriever military working dogs - an exomic exploratory study.

ABSTRACT: BACKGROUND:Canine lumbosacral stenosis is defined as narrowing of the caudal lumbar and/or sacral vertebral canal. A risk factor for neurologic problems in many large sized breeds, lumbosacral stenosis can also cause early retirement in Labrador retriever military working dogs. Though vital for conservative management of the condition, early detection is complicated by the ambiguous nature of clinical signs of lumbosacral stenosis in stoic and high-drive Labrador retriever military working dogs. Though clinical diagnoses of lumbosacral stenosis using CT imaging are standard, they are usually not performed unless dogs present with clinical symptoms. Understanding the underlying genomic mechanisms would be beneficial in developing early detection methods for lumbosacral stenosis, which could prevent premature retirement in working dogs. The exomes of 8 young Labrador retriever military working dogs (4 affected and 4 unaffected by lumbosacral stenosis, phenotypically selected by CT image analyses from 40 dogs with no reported clinical signs of the condition) were sequenced to identify and annotate exonic variants between dogs negative and positive for lumbosacral stenosis. RESULTS:Two-hundred and fifty-two variants were detected to be homozygous for the wild allele and either homozygous or heterozygous for the variant allele. Seventeen non-disruptive variants were detected that could affect protein effectiveness in 7 annotated (SCN1B, RGS9BP, ASXL3, TTR, LRRC16B, PTPRO, ZBBX) and 3 predicted genes (EEF1A1, DNAJA1, ZFX). No exonic variants were detected in any of the canine orthologues for human lumbar spinal stenosis candidate genes. CONCLUSIONS:TTR (transthyretin) gene could be a possible candidate for lumbosacral stenosis in Labrador retrievers based on previous human studies that have reported an association between human lumbar spinal stenosis and transthyretin protein amyloidosis. Other genes identified with exonic variants in this study but with no known published association with lumbosacral stenosis and/or lumbar spinal stenosis could also be candidate genes for future canine lumbosacral stenosis studies but their roles remain currently unknown. Human lumbar spinal stenosis candidate genes also cannot be ruled out as lumbosacral stenosis candidate genes. More definitive genetic investigations of this condition are needed before any genetic test for lumbosacral stenosis in Labrador retriever can be developed.

SUBMITTER: Mukherjee M

PROVIDER: S-EPMC5651560 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Lumbosacral stenosis in Labrador retriever military working dogs - an exomic exploratory study.

Mukherjee Meenakshi M Jones Jeryl C JC Yao Jianbo J

Canine genetics and epidemiology 20171023

<h4>Background</h4>Canine lumbosacral stenosis is defined as narrowing of the caudal lumbar and/or sacral vertebral canal. A risk factor for neurologic problems in many large sized breeds, lumbosacral stenosis can also cause early retirement in Labrador retriever military working dogs. Though vital for conservative management of the condition, early detection is complicated by the ambiguous nature of clinical signs of lumbosacral stenosis in stoic and high-drive Labrador retriever military worki ...[more]

PMID: 29085643

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Project description:Lumbosacral (LS) stenosis is a cause of lower back pain, loss of mission readiness, and early retirement in military working dogs (MWDs). Aims of the present two-part study were to evaluate a sample of German Shepherd MWDs using standard clinical criteria for LS pain, standard qualitative computed tomographic (CT) criteria for LS stenosis, novel quantitative CT criteria for LS stenosis, and novel behavioral classification criteria for LS pain. Data were retrieved from archives of a tertiary referral MWD hospital. Study 1 was a retrospective, observational, two-group design with a hypothesis that there would be a significant difference in the percentage of affected German Shepherd MWDs with multilevel stenosis (affecting ≥ 3 vertebrae) between LS pain groups, based on standard clinical and qualitative CT criteria. Study 2 was a retrospective, observational, cross-sectional, two- and three-group study design with a hypothesis that quantitative CT measurements would significantly differ between LS pain groups, assigned based on 3 classification systems. The 1st classification system used standard clinical criteria, while the 2nd and 3rd novel classifications included behavioral signs of LS pain. The following quantitative CT measures were recorded without knowledge of behavioral classification: vertebral foramen area, vertebral foramen volume, vertebral foramen fat area; and ratios of vertebral foramen area/vertebral body area (foramen area ratio), cranial vertebral foramen area/caudal vertebral foramen area (cranial:caudal foramen area ratio), and vertebral fat area/vertebral body area (fat area ratio). Study 1 findings did not support the hypothesis in that there was no significant difference in the percentage of dogs affected with multilevel stenosis between LS pain groups (P = 0.6567). Findings for study 2 supported the hypothesis in that dogs with LS pain were significantly more affected by multilevel stenosis (P = 0.0273). Significant differences occurred between LS pain groups in select vertebral locations for all measurements (P ≤ 0.05) except vertebral foramen area and vertebral foramen volume (P > 0.05). Comparisons using novel quantitative CT measures and behavioral classification criteria identified significant differences between LS pain groups that were not detected using standard qualitative criteria. These novel quantitative and behavioral classification criteria may be helpful in future research on causes for early retirement in German Shepherd MWDs.

Project description:BackgroundObesity in dogs is an increasing problem associated with morbidity, shortened life span and poor life quality. Overweight dogs exhibit postprandial hyperlipidaemia, highlighting the need to identify potential dysregulations in lipid metabolism. This study investigated metabolites related to lipid metabolism (i.e. acylcarnitines and taurine) and phospholipids in a feed-challenge test and aimed to identify metabolic variations in spontaneously overweight dogs. Twenty-eight healthy male Labrador Retriever dogs were included, 12 of which were classified as lean (body condition score (BCS) 4-5 on a 9-point scale) and 16 as overweight (BCS 6-8). After overnight fasting (14-17 h), fasting blood samples were collected and dogs were fed a high-fat meal followed by postprandial blood sample collection hourly for 4 h. Liquid chromatography-time of flight mass spectrometry (LC-TOFMS) was used to identify plasma metabolites and phospholipids. Multivariate models, mixed model repeated measures and linear regression analyses were used for data interpretation.ResultsIn all dogs, propionylcarnitine, stearoylcarnitine and nine phospholipids increased in response to food intake, while vaccenylcarnitine decreased (P ≤ 0.005 for all). Overall, carnitine and acetylcarnitine signal areas in the feed-challenge test were lower in overweight dogs (P ≤ 0.004). Notably, fasting plasma acetylcarnitine was lower in overweight dogs than in lean dogs (P = 0.001) and it did not change in response to feeding. The latter finding was in contrast to the decreased acetylcarnitine signal area found in lean dogs at one hour postprandially (P < 0.0001). One fasting phosphatidylcholine (PCaa C38:4) was higher in prominently overweight dogs (BCS > 6) than in lean dogs (P < 0.05).ConclusionsPlasma carnitine status was overall lower in spontaneously overweight dogs than in lean dogs in this cohort of healthy Labrador Retriever dogs, indicating a potential carnitine insufficiency in the overweight group. The acetylcarnitine response in overweight dogs indicated decreased fatty acid oxidation at fasting and metabolic inflexibility to food intake. Further studies on metabolic inflexibility and its potential role in the metabolism of overweight dogs are warranted.

Project description:Background:Dogs have human-directed social skills that allow them to communicate and cooperate with humans. We have previously identified two loci on chromosome 26 associated with human contact-seeking behaviors during an unsolvable problem task in laboratory beagles (Persson et al., 2016). The aim of the present study was to verify the single nucleotide polymorphisms (SNPs) in additional dog breeds. We also studied how the allele frequencies have changed during domestication and recent selection. Methods:Dogs of two breeds, 61 golden retrievers and 100 Labrador retrievers, were phenotyped and genotyped, and 19 wolves were genotyped. The Labrador retrievers were divided into common and field type by pedigree data to make it possible to study the effects of recent selection. All dogs were tested in an unsolvable problem task where human-directed social behaviors were scored. DNA from dogs (buccal swabs) and wolves (blood or brain tissue) was analyzed for genotype on two of the previously identified SNP markers, BICF2G630798942 (SNP1) and BICF2S23712114 (SNP2), by pyrosequencing. Results:There was genetic variation for SNP1 in both dog breeds whereas the wolves were fixed for this polymorphism, and for SNP2 there was variation in both dogs and wolves. For both SNPs, Labrador retriever types differed significantly in allele frequencies. We found associations between SNPs and human-directed social behavior in both dog breeds. In golden retrievers, SNP1 was associated with physical contact variables, for example, with the duration of physical contact with the owner (F 2,56 = 4.389, p = 0.017). SNP2 was associated with several behavioral variables in both breeds, among others owner gazing frequency in both golden retrievers (F 2,55 = 6.330, p = 0.003) and Labradors (F 1,93 = 5.209, p = 0.025). Discussion:Our results verify the association between the previously identified SNPs and human-directed social behavior scored in an unsolvable problem task. Differences in allele frequencies suggest that these loci have been affected by selection. The results indicate that these genomic regions are involved in human-directed social behavior in not only beagles but in other dog breeds as well. We hypothesize that they may have been important during dog domestication.

Project description:Obesity in dogs is an emerging issue that affects canine health and well-being. Its development is ascribed to several factors, including genetic predisposition and dietary management, and recent evidence suggests that intestinal microbiota may be involved as well. Previous works have shown obesity to be linked to significant changes in gut microbiota composition in humans and mice, but only limited information is available on the role played by canine gut microbiota. The aim of this exploratory study was to investigate whether composition of canine faecal microbiota may be influenced by overweight condition and breed. All the enrolled companion dogs were young adults, intact, healthy, and fed commercial extruded pet food; none had received antibiotics, probiotics or immunosuppressant drugs in the previous six months. Labrador Retriever (LR) and Border Collie (BC) were chosen as reference breeds and Body Condition Score (BCS) on a 9-point scale as reference method for evaluating body fat. The faecal microbial communities of 15 lean (BCS 4-5/9; 7 LRs and 8 BCs) and 14 overweight (BCS > 5/9; 8 LRs and 6 BCs) family dogs were analysed using 16S rRNA gene sequencing. Moreover, for each dog, the daily intake of energy (kcal/d) and dietary macronutrients (g/d) were calculated according to an accurate feeding history collection. Firmicutes and Bacteroidetes resulted the predominant phyla (51.5 ± 10.0% and 33.4 ± 8.5%, respectively) in all dogs. Bioinformatic and statistical analysis revealed that no bacterial taxon differed significantly based on body condition, except for genus Allisonella (p < 0.05); BC gut microbiota was richer (p < 0.05) in bacteria belonging to phyla Actinobacteria (family Coriobacteriaceae in particular) and Firmicutes (Allobaculum and Roseburia genera). No remarkable differences were recorded either for diversity indices (i.e., alpha diversity, p > 0.10) or for divergence within the sample set (i.e., beta diversity, p > 0.05). PERMANOVA tests performed on single factors demonstrated the tendency of dietary protein to influence the recruited dogs' microbiota beta-diversity at amplicon sequence variant level (p = 0.08). In conclusion, the faecal microbiota of dogs involved in this exploratory study showed no major variations based on body condition. However, our findings suggested that certain bacterial taxa previously acknowledged in obesity-related studies may be detected in dissimilar amounts depending on canine breed.

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Dataset Information

Lumbosacral stenosis in Labrador retriever military working dogs - an exomic exploratory study.

Publications

Lumbosacral stenosis in Labrador retriever military working dogs - an exomic exploratory study.

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