Advancing Genetic Selection and Behavioral Genomics of Working Dogs Through Collaborative Science

The ancient partnership between people and dogs is struggling to meet modern day needs, with demand exceeding our capacity to safely breed high-performing and healthy dogs. New statistical genetic approaches and genomic technology have the potential to revolutionize dog breeding, by transitioning from problematic phenotypic selection to methods that can preserve genetic diversity while increasing the proportion of successful dogs. To fully utilize this technology will require ultra large datasets, with hundreds of thousands of dogs. Today, dog breeders struggle to apply even the tools available now, stymied by the need for sophisticated data storage infrastructure and expertise in statistical genetics. Here, we review recent advances in animal breeding, and how a new approach to dog breeding would address the needs of working dog breeders today while also providing them with a path to realizing the next generation of technology. We provide a step-by-step guide for dog breeders to start implementing estimated breeding value selection in their programs now, and we describe how genotyping and DNA sequencing data, as it becomes more widely available, can be integrated into this approach. Finally, we call for data sharing among dog breeding programs as a path to achieving a future that can benefit all dogs, and their human partners too

Combining Citizen Science and Genomics to Investigate Tick, Pathogen, and Commensal Microbiome at Single-Tick Resolution

The prevalence of tickborne diseases worldwide is increasing virtually unchecked due to the lack of effective control strategies. The transmission dynamics of tickborne pathogens are influenced by the tick microbiome, tick co-infection with other pathogens, and environmental features. Understanding this complex system could lead to new strategies for pathogen control, but will require large-scale, high-resolution data. Here, we introduce Project Acari, a citizen science-based project to assay, at single-tick resolution, species, pathogen infection status, microbiome profile, and environmental conditions of tens of thousands of ticks collected from numerous sites across the United States. In the first phase of the project, we collected more than 2,400 ticks wild-caught by citizen scientists and developed high-throughput methods to process and sequence them individually. Applying these methods to 192 Ixodes scapularis ticks collected in a region with a high incidence of Lyme disease, we found that 62% were colonized by Borrelia burgdorferi, the Lyme disease pathogen. In contrast to previous reports, we did not find an association between the microbiome diversity of a tick and its probability of carrying B. burgdorferi. However, we did find undescribed associations between B. burgdorferi carriage and the presence of specific microbial taxa within individual ticks. Our findings underscore the power of coupling citizen science with high-throughput processing to reveal pathogen dynamics. Our approach can be extended for massively parallel screening of individual ticks, offering a powerful tool to elucidate the ecology of tickborne disease and to guide pathogen-control initiatives

Psychogenic Stress in Hospitalized Dogs: Cross Species Comparisons, Implications for Health Care, and the Challenges of Evaluation

Evidence to support the existence of health consequences of psychogenic stress has been documented across a range of domestic species. A general understanding of methods of recognition and means of mitigation of psychogenic stress in hospitalized animals is arguably an important feature of the continuing efforts of clinicians to improve the well-being and health of dogs and other veterinary patients. The intent of this review is to describe, in a variety of species: the physiology of the stress syndrome, with particular attention to the hypothalamic-pituitary-adrenal axis; causes and characteristics of psychogenic stress; mechanisms and sequelae of stress-induced immune dysfunction; and other adverse effects of stress on health outcomes. Following that, we describe general aspects of the measurement of stress and the role of physiological measures and behavioral signals that may predict stress in hospitalized animals, specifically focusing on dogs

Transcriptome Analysis in Domesticated Species: Challenges and Strategies

Domesticated species occupy a special place in the human world due to their economic and cultural value. In the era of genomic research, domesticated species provide unique advantages for investigation of diseases and complex phenotypes. RNA sequencing, or RNA-seq, has recently emerged as a new approach for studying transcriptional activity of the whole genome, changing the focus from individual genes to gene networks. RNA-seq analysis in domesticated species may complement genome-wide association studies of complex traits with economic importance or direct relevance to biomedical research. However, RNA-seq studies are more challenging in domesticated species than in model organisms. These challenges are at least in part associated with the lack of quality genome assemblies for some domesticated species and the absence of genome assemblies for others. In this review, we discuss strategies for analyzing RNA-seq data, focusing particularly on questions and examples relevant to domesticated species

Behavioral predictors of subsequent respiratory illness signs in dogs admitted to an animal shelter.

Individual variability is evident in behavior and physiology of animals. Determining whether behavior at intake may predict subsequent illness in the animal shelter may influence the management of dogs housed at animal shelters and reduce overall disease. While normally associated with mild disease and low mortality rates, respiratory disease nevertheless poses significant challenges to the management of dogs in the stressful environment of animal shelters due to its highly infectious nature. Therefore, the aim of the study was to explore whether behavior at intake can predict subsequent occurrence and progression of upper respiratory disease in dogs at animal shelters. In a correlational study, 84 dogs were assessed throughout their stay at a city animal shelter. The dogs were subjected to a behavioral assessment, 1 min in-kennel behavioral observations across two observation periods, and the collection of urinary cortisol:creatinine (C:C) ratio. The occurrence and progression of upper respiratory disease was monitored through repeated clinical exams (rectal temperature and the occurrence of nasal and ocular discharge, and presence of coughing and sneezing). A basic PLS Path regression model revealed that time in the shelter (estimate = .53, p < .001), and sociability (estimate = .24, p < .001) and curiosity scores (estimate = .09, p = .026) were associated with increased illness. Activity and anxiety scores, however, were not associated with illness. Urinary C:C, taken on the first full day, did not predict subsequent illness when accounting for time. Limitations included attrition of dogs, a small percentage receiving vaccinations, and continuous and non-systematic rotation of dogs in the kennels. Understanding if behavior can predict subsequent illness may improve shelter management practices, and in turn, result in improved live-release outcomes

Anterior Pituitary Transcriptome Suggests Differences in ACTH Release in Tame and Aggressive Foxes

Domesticated species exhibit a suite of behavioral, endocrinological, and morphological changes referred to as “domestication syndrome.” These changes may include a reduction in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and specifically reduced adrenocorticotropic hormone release from the anterior pituitary. To investigate the biological mechanisms targeted during domestication, we investigated gene expression in the pituitaries of experimentally domesticated foxes (Vulpes vulpes). RNA was sequenced from the anterior pituitary of six foxes selectively bred for tameness (“tame foxes”) and six foxes selectively bred for aggression (“aggressive foxes”). Expression, splicing, and network differences identified between the two lines indicated the importance of genes related to regulation of exocytosis, specifically mediated by cAMP, organization of pseudopodia, and cell motility. These findings provide new insights into biological mechanisms that may have been targeted when these lines of foxes were selected for behavior and suggest new directions for research into HPA axis regulation and the biological underpinnings of domestication

BarkBase : Epigenomic Annotation of Canine Genomes

Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly for complex diseases like cancer. Comprehensive genomic annotation of regulatory elements active in healthy canine tissues is crucial both for identifying candidate causal variants and for designing functional studies needed to translate genetic associations into disease insight. Currently, canine geneticists rely primarily on annotations of the human or mouse genome that have been remapped to dog, an approach that misses dog-specific features. Here, we describe BarkBase, a canine epigenomic resource available at barkbase.org. BarkBase hosts data for 27 adult tissue types, with biological replicates, and for one sample of up to five tissues sampled at each of four carefully staged embryonic time points. RNA sequencing is complemented with whole genome sequencing and with assay for transposase-accessible chromatin using sequencing (ATAC-seq), which identifies open chromatin regions. By including replicates, we can more confidently discern tissue-specific transcripts and assess differential gene expression between tissues and timepoints. By offering data in easy-to-use file formats, through a visual browser modeled on similar genomic resources for human, BarkBase introduces a powerful new resource to support comparative studies in dogs and humans

BarkBase : Epigenomic Annotation of Canine Genomes

Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly for complex diseases like cancer. Comprehensive genomic annotation of regulatory elements active in healthy canine tissues is crucial both for identifying candidate causal variants and for designing functional studies needed to translate genetic associations into disease insight. Currently, canine geneticists rely primarily on annotations of the human or mouse genome that have been remapped to dog, an approach that misses dog-specific features. Here, we describe BarkBase, a canine epigenomic resource available at barkbase.org. BarkBase hosts data for 27 adult tissue types, with biological replicates, and for one sample of up to five tissues sampled at each of four carefully staged embryonic time points. RNA sequencing is complemented with whole genome sequencing and with assay for transposase-accessible chromatin using sequencing (ATAC-seq), which identifies open chromatin regions. By including replicates, we can more confidently discern tissue-specific transcripts and assess differential gene expression between tissues and timepoints. By offering data in easy-to-use file formats, through a visual browser modeled on similar genomic resources for human, BarkBase introduces a powerful new resource to support comparative studies in dogs and humans

Red fox genome assembly identifies genomic regions associated with tame and aggressive behaviours

Strains of red fox (Vulpes vulpes) with markedly different behavioural phenotypes have been developed in the famous long-term selective breeding programme known as the Russian farm-fox experiment. Here we sequenced and assembled the red fox genome and re-sequenced a subset of foxes from the tame, aggressive and conventional farm-bred populations to identify genomic regions associated with the response to selection for behaviour. Analysis of the re-sequenced genomes identified 103 regions with either significantly decreased heterozygosity in one of the three populations or increased divergence between the populations. A strong positional candidate gene for tame behaviour was highlighted: SorCS1, which encodes the main trafficking protein for AMPA glutamate receptors and neurexins and suggests a role for synaptic plasticity in fox domestication. Other regions identified as likely to have been under selection in foxes include genes implicated in human neurological disorders, mouse behaviour and dog domestication. The fox represents a powerful model for the genetic analysis of affiliative and aggressive behaviours that can benefit genetic studies of behaviour in dogs and other mammals, including humans