A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs.
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ABSTRACT:
SUBMITTER: Raffan E
PROVIDER: S-EPMC4873617 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
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A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs.
Raffan Eleanor E Dennis Rowena J RJ O'Donovan Conor J CJ Becker Julia M JM Scott Robert A RA Smith Stephen P SP Withers David J DJ Wood Claire J CJ Conci Elena E Clements Dylan N DN Summers Kim M KM German Alexander J AJ Mellersh Cathryn S CS Arendt Maja L ML Iyemere Valentine P VP Withers Elaine E Söder Josefin J Wernersson Sara S Andersson Göran G Lindblad-Toh Kerstin K Yeo Giles S H GS O'Rahilly Stephen S
Cell metabolism 20160503 5
Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the β-MSH and β-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motiva ...[more]
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Project description:BackgroundDiabetes mellitus (DM) in dogs is a common endocrinopathy with a complex genetic architecture. Disease susceptibility in several breeds is associated with polymorphisms in immune response genes, but in the Labrador retriever breed, no genetic associations with DM have been identified. A deletion in the pro-opiomelanocortin (POMC) gene in Labrador retrievers is associated with increased appetite and risk of obesity.Hypothesis/objectivesTo characterize the POMC deletion in Labrador retrievers, to develop a simple genetic test for this mutation, and to test the hypothesis that the POMC gene deletion is associated with an increased risk of DM in this breed.AnimalsSixty-one non-diabetic Labrador retrievers aged >6 years and 57 Labrador retrievers with DM.MethodsCase-control genotyping study to compare the frequency of the POMC deletion in dogs with and without DM. After polymerase chain reaction (PCR) and sequencing to characterize the mutation, a PCR-based test was developed and validated using 2 different restriction fragment length polymorphism assays.ResultsA 14-base-pair deletion was confirmed and localized to exon 3 of the canine POMC gene. A PCR-based test for the deletion was successfully developed. There was no association between the presence of the POMC deletion mutation and DM in this population of Labrador retriever dogs (P = .31).Conclusions and clinical importanceThis study adds to the existing scientific literature indicating that there is little evidence for a direct link between obesity and DM in dogs.
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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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Project description: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.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 ?g/ml, respectively, p?<?0.0075), and the Labrador-golden crosses having intermediate levels (3.77?±?0.48 ?g/ml). Although several novel SNPs were identified in LCN1, there were no significant breed-specific sequence differences in the gene and no association of LCN1 genotypes with Can f 1 expression.As service dogs, Labrador retrievers likely have lower allergenic potential and, though there were no DNA sequence differences identified, classical genetic selection on the estimated breeding values associated with salivary Can f 1 expression may further reduce that potential.
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Project description: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.
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Project description:BackgroundThere are limited reports of severe tricuspid valve stenosis in dogs and limited data regarding treatment and outcome.ObjectiveTo evaluate clinical signs, echocardiographic features, and outcome of balloon valvuloplasty (BV) in dogs with severe tricuspid valve stenosis (TVS) in which BV was attempted.AnimalsFive client-owned dogs with severe TVS.MethodsRecords were retrospectively reviewed and data collected regarding signalment, clinical signs, diagnostic findings, procedures, and outcome.ResultsAll dogs were Labrador Retrievers. Presenting complaints included episodic weakness/syncope (4/5), abdominal distension (4/5), lethargy (2/5), and exercise intolerance (2/5). The median and range of measurements before BV were as follows: TV mean velocity 1.5 m/s (range 1.4-1.7 m/s); velocity-time integral (VTI) 79.8 cm (42.4-99.1 cm); and TV maximum velocity 2.9 m/s (2.3-3.2 m/s). Measurements (available for 3 of 5 dogs) after BV were as follows: TV mean velocity 1.15 m/s (0.9-1.4 m/s); VTI 44.95 cm (41.4-54.8 cm); and TV maximum velocity 1.15 m/s (1.9-2.3 m/s). The procedure was attempted in all dogs and completed in 4/5 dogs. The largest balloon diameter ranged from 15 mm to 25 mm, and length ranged from 4 cm to 5 cm. Right atrial pressure decreased in 4/5 dogs. All but 1 dog had clinical improvement after BV, but recurrence of clinical signs occurred (2/5). Tricuspid regurgitation worsened in 1 dog culminating in right heart failure and euthanasia.Conclusions and clinical importanceBV can be an effective treatment; however, clinical signs can recur. Right heart failure due to worsened TR is a potential complication in dogs with pre-existing moderate-to-severe TR.
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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.
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Project description:It is widely accepted that canine breeds stand and move differently. The prevalence of various musculoskeletal disorders such as hip and elbow dysplasia is also different between breeds. German shepherd dog (GSD) and Labrador retriever dog (LRD) are two large breeds with different conformations that have high prevalence of these disorders. This study quantifies the movement and standing posture of twelve healthy GSDs and twelve healthy LRDs to identify biomechanical similarities and differences that may be linked to sub-optimal hip and elbow mechanics. A pressure walkway and a motion capture system obtained measures of kinetics, kinematics and conformation during standing and trot. During standing, LRDs carry a greater percentage of the weight on the forelimbs (69%±5% vs. GSDs: 62%±2%, p<0.001) and their body Centre of Pressure (CoP) is located more cranially (p<0.001). GSDs had a greater pelvic tilt (79°±8 vs. 66°±9°, p = 0.004), more flexed stifles (44°±9° vs. LRDs: 34°±10°, p<0.05) and hocks (58°±11° vs. 26°±9°, p<0.01) and more extended hips (-10°±11° vs. 30°±12°, p<0.001). During trot, the GSDs' CoP had a longer anterior-posterior trajectory (151%±22% vs. LRDs: 93%±25% of the withers height, p<0.001). Stride parameters and loading of limbs were similar when normalised to the size and weight of the dog, respectively. The LRDs had a more extended thoracolumbar angle (p<0.001) and a less flexed lumbosacral angle (p<0.05). The LRDs' hip remained flexed during trot whereas the GSDs' hip joint was less flexed during swing (p<0.001) and more extended in late stance and early swing (p<0.001). In conclusion, the LRDs and GSDs differ in the way they stand and move and this would result in different loading pattern of the joints. Further investigation is required to determine the extent to which biomechanical differences are linked to musculoskeletal problems presented clinically.
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