Katriina Tiira

Do dominants have higher heterozygosity? Social status and genetic variation in brown trout, Salmo trutta

A key question of evolutionary importance is what factors influence who becomes dominant. Individual genetic variation has been found to be associated with several fitness traits, including behaviour. Could it also be a factor influencing social dominance? We investigated the association between social status and the amount of intra-individual genetic variation in juvenile brown trout (Salmo trutta). Genetic variation was estimated using 12 microsatellite loci. Dominant individuals had higher mean heterozygosity than subordinates in populations with the longest hatchery background. Heterozygosity–heterozygosity correlations did not find any evidence of inbreeding; however, single-locus analysis revealed four loci that each individually differed significantly between dominant and subordinate fish, thus giving more support to local than general effect as the mechanism behind the observed association between genetic diversity and a fitness-associated trait. We did not find any significant relation between mean d2 and social status, or internal relatedness and social status. Our results suggest that individual genetic variation can influence dominance relations, but manifestation of this phenomenon may depend on the genetic background of the population.

Aggressiveness is associated with genetic diversity in landlocked salmon (Salmo salar)

The amount of intraindividual genetic variation has often been found to have profound effects on life history traits. However, studies concerning the relationship between behaviour and genetic diversity are scarce. Aggressiveness is an important component of competitive ability in juvenile salmonids affecting their later performance and survival. In this study, we used an experimental approach to test the prediction that juveniles with low estimated genetic diversity should be less aggressive than juveniles with high estimated genetic diversity in fry from a highly endangered population of land‐locked salmon (Salmo salar). This was achieved by using a method enabling the accurate estimation of offspring genetic diversity based on parental microsatellite genotype data. This allowed us to create two groups of offspring expected to have high or low genetic diversity in which aggressive behaviour could be compared. Salmon fry with low estimated genetic diversity were significantly less aggressive than fry with high estimated genetic diversity. Closer analysis of the data suggested that this difference was due to differences in more costly acts of aggression. Our result may reflect a direct effect of genetic variation on a fitness‐related trait; however, we cannot rule out an alternative explanation of allele‐specific phenotype matching, where lowered aggression is expressed towards genetically more similar individuals.

Environmental Effects on Compulsive Tail Chasing in Dogs

Obsessive Compulsive Disorder (OCD) is a neuropsychiatric disorder observed both in humans and animals. Examples of Canine Compulsive Disorder (CD) include excessive tail chasing (TC), light/shadow chasing and flank sucking. We performed a questionnaire survey to investigate the characteristics of compulsive (TC) and its possible associations with environmental correlates and personality in a pet population of 368 dogs from four dog breeds. We observed an early onset of TC at 3–6 months of age and a large variation in TC frequency in all breeds, with an overrepresentation of milder cases. Almost half of the TC dogs showed lowered responsiveness during bouts and displayed also other types of compulsions more often than the controls. Interestingly, dogs that received dietary supplements, especially vitamins and minerals, expressed less TC compared to dogs that did not receive any supplements. Neutered females had less TC, suggesting an influence of ovarian hormones on TC. Tail chasers were shyer and had separated earlier from their mothers than the controls. Finally, our genetic study did not find an association between TC and CDH2, a locus previously associated with the canine flank sucking compulsion. In conclusion, the early-onset and the variable nature of the repetitive behaviour, which is affected by environmental factors such as micronutrients, neutering and maternal care, share several similar components between canine and human compulsions and supports canine TC as a model for human OCD.

A COL11A2 Mutation in Labrador Retrievers with Mild Disproportionate Dwarfism

We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

Early Life Experiences and Exercise Associate with Canine Anxieties

Personality and anxiety disorders across species are affected by genetic and environmental factors. Shyness-boldness personality continuum exists across species, including the domestic dog, with a large within- and across-breed variation. Domestic dogs are also diagnosed for several anxiety-related behavioral conditions, such as generalized anxiety disorders, phobias, and separation anxiety. Genetic and environmental factors contributing to personality and anxiety are largely unknown. We collected questionnaire data from a Finnish family dog population (N = 3264) in order to study the associating environmental factors for canine fearfulness, noise sensitivity, and separation anxiety. Early life experiences and exercise were found to associate with anxiety prevalence. We found that fearful dogs had less socialization experiences (p = 0.002) and lower quality of maternal care (p < 0.0001) during puppyhood. Surprisingly, the largest environmental factor associating with noise sensitivity (p < 0.0001) and separation anxiety (p = 0.007) was the amount of daily exercise; dogs with noise sensitivity and separation anxiety had less daily exercise. Our findings suggest that dogs share many of the same environmental factors that contribute to anxiety in other species as well, such as humans and rodents. Our study highlights the importance of early life experiences, especially the quality of maternal care and daily exercise for the welfare and management of the dogs, and reveals important confounding factors to be considered in the genetic characterization of canine anxiety.

Genetics and behavior: a guide for practitioners.

Phenotyping behavior is difficult, partly because behavior is almost always influenced by environment. Using objective terms/criteria to evaluate behaviors is best; the more objective the assessment, the more likely underlying genetic patterns will be identified. Behavioral pathologies, and highly desirable behavioral characteristics/traits, are likely complex, meaning that multiple genes are probably involved, and therefore simple genetic tests are less possible. Breeds can be improved using traditional quantitative genetic methods; unfortunately, this also creates the possibility of inadvertently selecting for covarying undesirable behaviors. Patterns of behaviors within families and breed lines are still the best guidelines for genetic counseling in dogs.

Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus

Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG), primary open-angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively) in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63×10−10, OR = 32 for homozygosity). Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease.

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long-Term Follow-Up Study

Background Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long‐term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult‐onset epilepsies. Hypothesis/Objectives The objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood. Animals A total of 25 LR with a history of BFJE and 91 control dogs of the same breed. Methods Owners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dogs activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case–control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy. Results Lagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood. Conclusions and Clinical Importance Although the long‐term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.

Non-targeted metabolite profiling reveals changes in oxidative stress, tryptophan and lipid metabolisms in fearful dogs

BackgroundAnxieties, such as shyness, noise phobia and separation anxiety, are common but poorly understood behavioural problems in domestic dogs, Canis familiaris. Although studies have demonstrated genetic and environmental contributions to anxiety pathogenesis, better understanding of the molecular underpinnings is needed to improve diagnostics, management and treatment plans. As a part of our ongoing canine anxiety genetics efforts, this study aimed to pilot a metabolomics approach in fearful and non-fearful dogs to identify candidate biomarkers for more objective phenotyping purposes and to refer to potential underlying biological problem.MethodsWe collected whole blood samples from 10 fearful and 10 non-fearful Great Danes and performed a liquid chromatography combined with mass spectrometry (LC–MS)-based non-targeted metabolite profiling.ResultsNon-targeted metabolomics analysis detected six 932 metabolite entities in four analytical modes [RP and HILIC; ESI(−) and ESI(+)], of which 239 differed statistically between the test groups. We identified changes in 13 metabolites (fold change ranging from 1.28 to 2.85) between fearful and non-fearful dogs, including hypoxanthine, indoxylsulfate and several phospholipids. These molecules are involved in oxidative stress, tryptophan and lipid metabolisms.ConclusionsWe identified significant alterations in the metabolism of fearful dogs, and some of these changes appear relevant to anxiety also in other species. This pilot study demonstrates the feasibility of the non-targeted metabolomics and warrants a larger replication study to confirm the role of the identified biomarkers and pathways in canine anxiety.

Urban environment predisposes dogs and their owners to allergic symptoms

Our companion-animals, dogs, suffer increasingly from non-communicable diseases, analogous to those common in humans, such as allergic manifestations. In humans, living in rural environments is associated with lower risk of allergic diseases. Our aim was to explore whether a similar pattern can be found in dogs, using a nation-wide survey in Finland (n = 5722). We characterised the land-use around dog’s home at the time of birth as well as around its current home, and described several lifestyle factors. The severity of owner-reported allergic symptoms in dogs was estimated with a comprehensive set of questions, developed by experts of canine dermatology. Also, the prevalence of diagnosed allergies in dog owners was recorded. The results indicate that allergic symptoms are more prevalent in urban environments both in dog owners and in dogs (accounting the effect of dog breed). Several factors related to rural living, such as bigger family size and regular contact with farm animals and other pets, were also protective against allergic symptoms in dogs. Interestingly, allergic dogs were more likely to have allergic owners than healthy dogs were. Therefore, we suggest that the mutual presence of allergic symptoms in both species indicates common underlying causal factors of allergic diseases.