Knowledge on the genetic epidemiology of disorders in the dog population has implications for both veterinary medicine and sustainable breeding. Limited data on frequencies of genetic disease variants across breeds exists, and the disease heritage of mixed breed dogs remains poorly explored to date. Advances in genetic screening technologies now enable comprehensive investigations of the canine disease heritage, and generate health-related big data that can be turned into action. We pursued population screening of genetic variants implicated in Mendelian disorders in the largest canine study sample examined to date by examining over 83,000 mixed breed and 18,000 purebred dogs representing 330 breeds for 152 known variants using a custom-designed beadchip microarray. We further announce the creation of MyBreedData (www.mybreeddata.com), an online updated inherited disorder prevalence resource with its foundation in the generated data. We identified the most prevalent, and rare, disease susceptibility variants across the general dog population while providing the first extensive snapshot of the mixed breed disease heritage. Approximately two in five dogs carried at least one copy of a tested disease variant. Most disease variants are shared by both mixed breeds and purebreds, while breed- or line-specificity of others is strongly suggested. Mixed breed dogs were more likely to carry a common recessive disease, whereas purebreds were more likely to be genetically affected with one, providing DNA-based evidence for hybrid vigor. We discovered genetic presence of 22 disease variants in at least one additional breed in which they were previously undescribed. Some mutations likely manifest similarly independently of breed background; however, we emphasize the need for follow up investigations in each case and provide a suggested validation protocol for broader consideration. In conclusion, our study provides unique insight into genetic epidemiology of canine disease risk variants, and their relevance for veterinary medicine, breeding programs and animal welfare. Like any human, dogs may suffer from or pass on a variety of inherited disorders. Knowledge of how likely a typical dog is to carry an inherited disorder in its genome, and which disorders are the most common and relevant ones across dog breeds, is valuable for both veterinary care and breeding of healthy dogs. We have explored the largest global dog study sample collected to date, consisting of more than 100,000 mixed breed and purebred dogs, to advance research on this subject. We found that mixed breed dogs and purebred dogs potentially suffer from many of the same inherited disorders, and that around two in five dogs carried at least one of the conditions that we screened for. A dog carrying an inherited disorder is not a “bad dog”–but we humans responsible for breeding selections do need to make sustainable decisions avoiding inbreeding, i.e. mating of dogs that are close relatives. The disease prevalence information we generated during this study is made available online (www.mybreeddata.com), as a free tool for breed and kennel clubs, breeders, as well as the veterinary and scientific community.

A rural environment and farming lifestyle are known to provide protection against allergic diseases. This protective effect is expected to be mediated via exposure to environmental microbes that are needed to support a normal immune tolerance. However, the triangle of interactions between environmental microbes, host microbiota, and immune system remains poorly understood. Here, we have studied these interactions using a canine model (two breeds, n = 169), providing an intermediate approach between complex human studies and artificial mouse model studies. We show that the skin microbiota reflects both the living environment and the lifestyle of a dog. Remarkably, the prevalence of spontaneous allergies is also associated with residential environment and lifestyle, such that allergies are most common among urban dogs living in single-person families without other animal contacts, and least common among rural dogs having opposite lifestyle features. Thus, we show that living environment and lifestyle concurrently associate with skin microbiota and allergies, suggesting that these factors might be causally related. Moreover, microbes commonly found on human skin tend to dominate the urban canine skin microbiota, while environmental microbes are rich in the rural canine skin microbiota. This in turn suggests that skin microbiota is a feasible indicator of exposure to environmental microbes. As short-term exposure to environmental microbes via exercise is not associated with allergies, we conclude that prominent and sustained exposure to environmental microbiotas should be promoted by urban planning and lifestyle changes to support health of urban populations. Significance Urban, Westernized populations suffer extensively from noncommunicable diseases such as allergies. However, the overlapping effects of living environment and lifestyle are difficult to separate. Intriguingly, also our fellow animals, dogs, suffer from analogous diseases. Therefore, we suggest that pet dogs, sharing their environment and lifestyle with humans but having a comparatively simple life, provide a valuable model for understanding origins of noncommunicable diseases. We show that living environment and lifestyle concurrently, but still independently, shape both the skin microbiota and the risk of allergic disease in dogs. Urbanized lifestyle, featuring restricted animal contacts and small family size, is allergy promoting both in rural and urban dogs. Hence, both environment and lifestyle seem to influence the microbiota and, probably consequently, immune tolerance.

Primary glaucoma is one of the most common causes of irreversible blindness both in humans and in dogs. Glaucoma is an optic neuropathy affecting the retinal ganglion cells and optic nerve, and elevated intraocular pressure is commonly associated with the disease. Glaucoma is broadly classified into primary open angle (POAG), primary closed angle (PCAG) and primary congenital glaucoma (PCG). Human glaucomas are genetically heterogeneous and multiple loci have been identified. Glaucoma affects several dog breeds but only three loci and one gene have been implicated so far. We have investigated the genetics of primary glaucoma in the Norwegian Elkhound (NE). We established a small pedigree around the affected NEs collected from Finland, US and UK and performed a genome-wide association study with 9 cases and 8 controls to map the glaucoma gene to 750 kb region on canine chromosome 20 (p_raw = 4.93×10⁻⁶, p_genome = 0.025). The associated region contains a previously identified glaucoma gene, ADAMTS10, which was subjected to mutation screening in the coding regions. A fully segregating missense mutation (p.A387T) in exon 9 was found in 14 cases and 572 unaffected NEs (p_Fisher = 3.5×10⁻²⁷) with a high carrier frequency (25.3%). The mutation interrupts a highly conserved residue in the metalloprotease domain of ADAMTS10, likely affecting its functional capacity. Our study identifies the genetic cause of primary glaucoma in NEs and enables the development of a genetic test for breeding purposes. This study establishes also a new spontaneous canine model for glaucoma research to study the ADAMTS10 biology in optical neuropathy.

The growing number of identified genetic disease risk variants across dog breeds challenges the current state-of-the-art of population screening, veterinary molecular diagnostics, and genetic counseling. Multiplex screening of such variants is now technologically feasible, but its practical potential as a supportive tool for canine breeding, disease diagnostics, pet care, and genetics research is still unexplored. To demonstrate the utility of comprehensive genetic panel screening, we tested nearly 7000 dogs representing around 230 breeds for 93 disease-associated variants using a custom-designed genotyping microarray (the MyDogDNA® panel test). In addition to known breed disease-associated mutations, we discovered 15 risk variants in a total of 34 breeds in which their presence was previously undocumented. We followed up on seven of these genetic findings to demonstrate their clinical relevance. We report additional breeds harboring variants causing factor VII deficiency, hyperuricosuria, lens luxation, von Willebrand’s disease, multifocal retinopathy, multidrug resistance, and rod-cone dysplasia. Moreover, we provide plausible molecular explanations for chondrodysplasia in the Chinook, cerebellar ataxia in the Norrbottenspitz, and familiar nephropathy in the Welsh Springer Spaniel. These practical examples illustrate how genetic panel screening represents a comprehensive, efficient and powerful diagnostic and research discovery tool with a range of applications in veterinary care, disease research, and breeding. We conclude that several known disease alleles are more widespread across different breeds than previously recognized. However, careful follow up studies of any unexpected discoveries are essential to establish genotype-phenotype correlations, as is readiness to provide genetic counseling on their implications for the dog and its breed.

The dog, Canis lupus familiaris, is an important model for studying human diseases. Unlike many model organisms, the dog genome has a comparatively poor functional annotation, which hampers gene discovery for development, morphology, disease, and behavior. To fill this gap, we established a comprehensive tissue biobank for both the dog and wolf samples. The biobank consists of 5485 samples representing 132 tissues from 13 dogs, 12 dog embryos, and 24 wolves. In a subset of 100 tissues from nine dogs and 12 embryos, we characterized gene expression activity for each promoter, including alternative and novel, i.e., previously not annotated, promoter regions, using the 5’ targeting RNA sequencing technology STRT2-seq. We identified over 100,000 promoter region candidates in the recent canine genome assembly, CanFam4, including over 45,000 highly reproducible sites with gene expression and respective tissue enrichment levels. We provide a promoter and gene expression atlas with interactive, open data resources, including a data coordination center and genome browser track hubs. We demonstrated the applicability of Dog Genome Annotation (DoGA) data and resources using multiple examples spanning canine embryonic development, morphology and behavior, and diseases across species.

Experiments show that nitrogen-doped carbon nanotubes subjected to the electron beam in a transmission electron microscope can easily lose dopant atoms and that overall they are less stable under electron irradiation than the pristine tubes. To understand the lower stability of nitrogen-doped nanotubes we use a density-functional-theory-based tight-binding model and simulate impacts of energetic electrons onto the nanotubes. We show that the dopant atom displacement energy and thus the electron threshold energy is lower for nanotubes with smaller diameter and that, independent of the nanotube diameter, the dopant nitrogen atoms can be displaced more easily than the host carbon atoms. Our results set a limit on the threshold electron energy for damage production in N-doped tubes and indicate that spatially localized electron irradiation of doped nanotubes can be used for local atomic and band structure engineering.