Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies.
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ABSTRACT:
SUBMITTER: Norton EM
PROVIDER: S-EPMC8701027 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There has been considerable interest in studying cancer in dogs and its potential as a model system for humans. One area of research has been the search for genetic risk variants in canine lymphoma, which is amongst the most common canine cancers. Previous studies have focused on a limited number of breeds, but none have included Border Collies. The aims of this study were to identify relationships between Border Collie lymphoma cases through an extensive pedigree investigation and to utilise relationship information to conduct genome-wide association study (GWAS) analyses to identify risk regions associated with lymphoma. The expanded pedigree analysis included 83,000 Border Collies, with 71 identified lymphoma cases. The analysis identified affected close relatives, and a common ancestor was identified for 54 cases. For the genomic study, a GWAS was designed to incorporate lymphoma cases, putative "carriers", and controls. A case-control GWAS was also conducted as a comparison. Both analyses showed significant SNPs in regions on chromosomes 18 and 27. Putative top candidate genes from these regions included DLA-79, WNT10B, LMBR1L, KMT2D, and CCNT1.
| S-EPMC10536503 | biostudies-literature
Project description:In order to assess dogs' personality changes during ontogeny, a cohort of 69 Border collies was followed up from six to 18-24 months. When the dogs were 6, 12, and 18-24 months old, their owners repeatedly filled in a dog personality questionnaire (DPQ), which yielded five personality factors divided into fifteen facets. All five DPQ factors were highly correlated between the three age classes, indicating that the dogs' personality remained consistent relative to other individuals. Nonetheless, at the group level significant changes with age were found for four of the five DPQ factors. Fearfulness, Aggression towards People, Responsiveness to Training and Aggression towards Animals increased with age; only Activity/Excitability did not change significantly over time. These changes in DPQ factor scores occurred mainly between the ages of 6 and 12 months, although some facets changed beyond this age. No sex differences were found for any of the tested factors or facets, suggesting that individual variation in personality was greater than male/female differences. There were significant litter effects for the factors Fearfulness, Aggression towards People and Activity/Excitability, indicating either a strong genetic basis for these traits or a high influence of the shared early environment. To conclude, from the age of six months, consistency in personality relative to other individuals can be observed in Border collies. However, at the group level, increases in fearful and aggressive behaviours occur up to 12 months and for some traits up to two years, highlighting the need for early interventions. Follow-up studies are needed to assess trajectories of personality development prior to six months and after two years, and to include a wider variety of breeds.
| S-EPMC5295634 | biostudies-literature
Project description:Simple Summary Dog agility is a canine sport that has gained popularity among pet owners in recent decades. Because of the high-performance level, injuries to dogs competing in this sport are becoming frequent. The need for better knowledge of the anatomy of the structures involved in athletic movements is an essential starting point for correctly managing agility-related injuries. The aim of this paper was to investigate the ultrasonographic anatomy of the carpal joint, creating a baseline reference for the Border Collie, which is the breed most utilised in agility competitions. The data acquired could be of use in future studies regarding sport-induced injuries in the canine carpus. Abstract Recent literature has demonstrated that high-resolution ultrasonographic anatomy of the canine carpus is possible; however, only the structures of the dorsal face were described. The aims of this prospective study were: (1) to describe the normal ultrasonographic appearance of the carpal tendons in sporting Border Collies; (2) to measure the height, length, and thickness of the tendon at the radial ulnar notch level in order to create a baseline reference for the breed, and (3) to describe a standardised protocol to ultrasonographically evaluate the carpal faces and visible tendinous structures. A pilot study based on ten cadaveric front limbs was used to identify the structures. A subsequent clinical phase of the study using twenty-six Border Collies was recorded. The tendons of the Extensor Carpi Radialis, Extensor Digitorum Communis, and Extensor Digitorum Lateralis were identified and followed from the tenomuscular junction to the distal insertion on the dorsal face of the digits. On the lateral face, the tendon of the Extensor Carpi Ulnaris was recognised and followed. On the palmar face, the two heads of the Flexor Carpi Ulnaris tendon ending on the accessory carpal bone, the adjacent Flexor Digitorum Superficialis tendon, and the deep and medially located Flexor Digitorum Profundus tendon were seen and followed. The Flexor Carpi Radialis and the Abductor Pollicis Longus tendons were seen in the medial carpal face. The ulnar notch of the radius was used as the measurement and starting point of the ultrasonography. These data could be used as a standard reference in the case of chronic overuse and trauma-induced changes in the canine carpus.
| S-EPMC9404444 | biostudies-literature
Project description:BackgroundWhite spotting patterns in mammals can be caused by mutations in the genes for the endothelin B receptor and c-Kit, whose protein products are necessary for proper migration, differentiation or survival of the melanoblast population of cells. Although there are many different dog breeds that segregate white spotting patterns, no genes have been identified that are linked to these phenotypes.ResultsAn intercross was generated from a female Newfoundland and a male Border Collie and the white spotting phenotypes of the intercross progeny were evaluated by measuring percentage surface area of white in the puppies. The Border Collie markings segregated as a simple autosomal recessive (7/25 intercross progeny had the phenotype). Two candidate genes, for the endothelin B receptor (EDNRB) and c-Kit (KIT), were evaluated for segregation with the white spotting pattern. Polymorphisms between the Border Collie and Newfoundland were identified for EDNRB using Southern analysis after a portion of the canine gene had been cloned. Polymorphisms for KIT were identified using a microsatellite developed from a bacterial artificial chromosome containing the canine gene.ConclusionsBoth EDNRB and KIT were excluded as a cause of the white spotting pattern in at least two of the intercross progeny. Although these genes have been implicated in white spotting in other mammals, including horses, pigs, cows, mice and rats, they do not appear to be responsible for the white spotting pattern found in the Border Collie breed of dog.
| S-EPMC15016 | biostudies-literature
Project description:Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09 × 10(-13)). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-?B pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS-guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders.
| S-EPMC3441646 | biostudies-literature
Project description:Aging of attentiveness affects cognitive functions like perception and working memory, which can seriously impact communication between dogs and humans, potentially hindering training and cooperation. Previous studies have revealed that aged laboratory beagles and pet Border collies (BC) show a decline in selective attention. However, much less is known about the aging of attentiveness in pet dogs in general rather than in specific breeds. Using 185 pet dogs (75 BC and 110 dogs of other breeds) divided into three age groups [late adulthood (6- < 8 year), senior (8- < 10 year) and geriatric (≥10 year)], we assessed the progress of aging of attentional capture, sustained and selective attention in older dogs in order to explore if prior results in BC are generalizable and to evaluate the influence of lifelong training on measures of attention. Each dog's lifelong training score (ranging from 0 to 52) was calculated from a questionnaire filled in by the owners listing what kinds of training the dog participated in during its entire life. Dogs were tested in two tasks; the first, measuring attentional capture and sustained attention toward two stimuli (toy and human); and the second, measuring selective attention by means of clicker training for eye contact and finding food on the floor. In the first task, results revealed a significant effect of age but no effect of lifelong training on latency to orient to the stimuli. Duration of looking decreased with age and increased with lifelong training. In the second task, while lifelong training decreased the latency of dogs to form eye contact, aged dogs needed longer to find food. BC did not differ from other dogs in any measures of attention except latency to find food. In conclusion, aged dogs showed a decline in attentional capture and sustained attention demonstrating that these tests are sensitive to detect aging of attentiveness in older pet dogs. Importantly, selective attention remained unchanged with age and lifelong training seemed to delay or reduce the aging of attentiveness, further highlighting the importance of lifelong training in retaining general cognitive functions.
| S-EPMC5397477 | biostudies-literature
Project description:Recent studies suggest that the relationship between endogenous oxytocin and social affiliative behavior can be critically moderated by contextual and individual factors in humans. While oxytocin has been shown to influence human-directed affiliative behaviors in dogs, no study investigated yet how such factors moderate these effects. Our study aimed to investigate whether the context and the dogs' individual characteristics moderate the associations between the social affiliative (greeting) behavior and four single-nucleotide polymorphisms (SNPs) of the oxytocin receptor (OXTR) gene. We recorded the greeting behavior in three contexts: (1) when the dog first met an unfamiliar experimenter, (2) during a separation from the owner, and (3) after the experimenter approached the dog in a threatening manner. In the latter two contexts (during separation and after threatening), we categorized the dogs into stressed and non-stressed groups based on their behavior in the preceding situations. In line with previous studies, we found that polymorphisms in the OXTR gene are related to the greeting behavior of dogs. However, we also showed that the analyzed SNPs were associated with greeting in different contexts and in different individuals, suggesting that the four SNPs might be related to different functions of the oxytocin system. The -213A/G was associated with greeting only when the dog had no prior negative experience with the experimenter. The rs8679682 was found in association with greeting in all three contexts but these associations were significant only in non-stressed dogs. The -94T/C was associated with greeting only when the dog was stressed and had an interaction with the sex of the dog. The -74C/G SNP was associated with greeting only when the dog was stressed during separation and also had a sex interaction. Taken together, our results suggest that, similarly to humans, the effects of oxytocin on the dogs' social behavior are not universal, but constrained by features of situations and individuals. Understanding these constraints helps further clarify how oxytocin mediates social behavior which, in the long run, could improve the application of oxytocin in pharmacotherapy.
| S-EPMC5742244 | biostudies-literature
Project description:Imerslund-Gräsbeck syndrome (IGS) or selective cobalamin malabsorption has been described in humans and dogs. IGS occurs in Border Collies and is inherited as a monogenic autosomal recessive trait in this breed. Using 7 IGS cases and 7 non-affected controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 3.53 Mb interval on chromosome 2. We re-sequenced the genome of one affected dog at ∼10× coverage and detected 17 non-synonymous variants in the critical interval. Two of these non-synonymous variants were in the cubilin gene (CUBN), which is known to play an essential role in cobalamin uptake from the ileum. We tested these two CUBN variants for association with IGS in larger cohorts of dogs and found that only one of them was perfectly associated with the phenotype. This variant, a single base pair deletion (c.8392delC), is predicted to cause a frameshift and premature stop codon in the CUBN gene. The resulting mutant open reading frame is 821 codons shorter than the wildtype open reading frame (p.Q2798Rfs*3). Interestingly, we observed an additional nonsense mutation in the MRC1 gene encoding the mannose receptor, C type 1, which was in perfect linkage disequilibrium with the CUBN frameshift mutation. Based on our genetic data and the known role of CUBN for cobalamin uptake we conclude that the identified CUBN frameshift mutation is most likely causative for IGS in Border Collies.
| S-EPMC3628801 | biostudies-literature
Project description:BackgroundNeuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative disease, has been diagnosed in young adult Australian Cattle Dogs.ObjectiveCharacterize the Australian Cattle Dog form of NCL and determine its molecular genetic cause.AnimalsTissues from 4 Australian Cattle Dogs with NCL-like signs and buccal swabs from both parents of a fifth affected breed member. Archived DNA samples from 712 individual dogs were genotyped.MethodsTissues were examined by fluorescence, electron, and immunohistochemical microscopy. A whole-genome sequence was generated for 1 affected dog. A TaqMan allelic discrimination assay was used for genotyping.ResultsThe accumulation of autofluorescent cytoplasmic storage material with characteristic ultrastructure in tissues from the 4 affected dogs supported a diagnosis of NCL. The whole-genome sequence contained a homozygous nonsense mutation: CLN5:c.619C>T. All 4 DNA samples from clinically affected dogs tested homozygous for the variant allele. Both parents of the fifth affected dog were heterozygotes. Archived DNA samples from 346 Australian Cattle Dogs, 188 Border Collies, and 177 dogs of other breeds were homozygous for the reference allele. One archived Australian Cattle Dog sample was from a heterozygote.Conclusions and clinical importanceThe homozygous CLN5 nonsense is almost certainly causal because the same mutation previously had been reported to cause a similar form of NCL in Border Collies. Identification of the molecular genetic cause of Australian Cattle Dog NCL will allow the use of DNA tests to confirm the diagnosis of NCL in this breed.
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Project description:Whole-genome regression methods are being increasingly used for the analysis and prediction of complex traits and diseases. In human genetics, these methods are commonly used for inferences about genetic parameters, such as the amount of genetic variance among individuals or the proportion of phenotypic variance that can be explained by regression on molecular markers. This is so even though some of the assumptions commonly adopted for data analysis are at odds with important quantitative genetic concepts. In this article we develop theory that leads to a precise definition of parameters arising in high dimensional genomic regressions; we focus on the so-called genomic heritability: the proportion of variance of a trait that can be explained (in the population) by a linear regression on a set of markers. We propose a definition of this parameter that is framed within the classical quantitative genetics theory and show that the genomic heritability and the trait heritability parameters are equal only when all causal variants are typed. Further, we discuss how the genomic variance and genomic heritability, defined as quantitative genetic parameters, relate to parameters of statistical models commonly used for inferences, and indicate potential inferential problems that are assessed further using simulations. When a large proportion of the markers used in the analysis are in LE with QTL the likelihood function can be misspecified. This can induce a sizable finite-sample bias and, possibly, lack of consistency of likelihood (or Bayesian) estimates. This situation can be encountered if the individuals in the sample are distantly related and linkage disequilibrium spans over short regions. This bias does not negate the use of whole-genome regression models as predictive machines; however, our results indicate that caution is needed when using marker-based regressions for inferences about population parameters such as the genomic heritability.
| S-EPMC4420472 | biostudies-literature