Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes and health

Dogs are the most phenotypically diverse mammalian species, and they possess more known heritable disorders than any other non-human mammal. Efforts to catalog and characterize genetic variation across well-chosen populations of canines are necessary to advance our understanding of their evolutionary history and genetic architecture. To date, no organized effort has been undertaken to sequence the world's canid populations. The Dog10K Consortium (http://www.dog10kgenomes.org) is an international collaboration of researchers from across the globe who will generate 20× whole genomes from 10 000 canids in 5 years. This effort will capture the genetic diversity that underlies the phenotypic and geographical variability of modern canids worldwide. Breeds, village dogs, niche populations and extended pedigrees are currently being sequenced, and de novo assemblies of multiple canids are being constructed. This unprecedented dataset will address the genetic underpinnings of domestication, breed formation, aging, behavior and morphological variation. More generally, this effort will advance our understanding of human and canine health

The dog as an animal model for DISH?

Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic disorder of the axial and peripheral skeleton in humans and has incidentally been described in dogs. The aims of this retrospective radiographic cohort study were to determine the prevalence of DISH in an outpatient population of skeletally mature dogs and to investigate if dogs can be used as an animal model for DISH. The overall prevalence of canine DISH was 3.8% (78/2041). The prevalence of DISH increased with age and was more frequent in male dogs, similar to findings in human studies. In the Boxer breed the prevalence of DISH was 40.6% (28/69). Dog breeds represent closed gene pools with a high degree of familiar relationship and the high prevalence in the Boxer may be indicative of a genetic origin of DISH. It is concluded that the Boxer breed may serve as an animal model for DISH in humans

History and structure of the closed pedigreed population of Icelandic Sheepdogs

<p>Abstract</p> <p>Background</p> <p>Dog breeds lose genetic diversity because of high selection pressure. Breeding policies aim to minimize kinship and therefore maintain genetic diversity. However, policies like mean kinship and optimal contributions, might be impractical. Cluster analysis of kinship can elucidate the population structure, since this method divides the population in clusters of related individuals. Kinship-based analyses have been carried out on the entire Icelandic Sheepdog population, a sheep-herding breed.</p> <p>Results</p> <p>Analyses showed that despite increasing population size and deliberately transferring dogs, considerable genetic diversity has been lost. When cluster analysis was based on kinships calculated seven generation backwards, as performed in previous studies, results differ markedly from those based on calculations going back to the founder-population, and thus invalidate recommendations based on previous research. When calculated back to the founder-population, kinship-based clustering reveals the distribution of genetic diversity, similarly to strategies using mean kinship.</p> <p>Conclusion</p> <p>Although the base population consisted of 36 Icelandic Sheepdog founders, the current diversity is equivalent to that of only 2.2 equally contributing founders with no loss of founder alleles in descendants. The maximum attainable diversity is 4.7, unlikely achievable in a non-supervised breeding population like the Icelandic Sheepdog. Cluster analysis of kinship coefficients can provide a supporting tool to assess the distribution of available genetic diversity for captive population management.</p

A canine model of Cohen syndrome: Trapped Neutrophil Syndrome

<p>Abstract</p> <p>Background</p> <p>Trapped Neutrophil Syndrome (TNS) is a common autosomal recessive neutropenia in Border collie dogs.</p> <p>Results</p> <p>We used a candidate gene approach and linkage analysis to show that the causative gene for TNS is <it>VPS13B</it>. We chose <it>VPS13B </it>as a candidate because of similarities in clinical signs between TNS and Cohen syndrome, in human, such as neutropenia and a typical facial dysmorphism. Linkage analysis using microsatellites close to <it>VPS13B </it>showed positive linkage of the region to TNS. We sequenced each of the 63 exons of <it>VPS13B </it>in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein. Cohen syndrome patients present with mental retardation in 99% of cases, but learning disabilities featured in less than half of TNS affected dogs. It has been implied that loss of the alternate transcript of <it>VPS13B </it>in the human brain utilising an alternate exon, 28, may cause mental retardation. Mice cannot be used to test this hypothesis as they do not express the alternate exon. We show that dogs do express alternate transcripts in the brain utilising an alternate exon homologous to human exon 28.</p> <p>Conclusion</p> <p>Dogs can be used as a model organism to explore the function of the alternately spliced transcript of VPS13B in the brain. TNS in Border collies is the first animal model for Cohen syndrome and can be used to study the disease aetiology.</p

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Differences in trait impulsivity indicate diversification of dog breeds into working and show lines

Impulsiveness describes the inability to inhibit behaviour in the presence of salient cues. Trait-level impulsivity exists on a continuum and individual differences can be adaptive in different contexts. While breed related differences in behavioural tendency in the domestic dog (Canis familiaris) are well established, the phenomenon within lines of a breed which have been selected more recently is not well studied, although it may challenge the popular notion of breed-typical behaviour. We describe differences in impulsivity between and within two dog breeds with working and show lines selected for different levels of impulsivity: Border Collies (herding work) and Labrador Retrievers (gun work). Recent show line selection might have lessened differences in impulsivity between breeds. We tested this hypothesis on a dataset of 1161 individuals assessed using a validated psychometric tool (Dog Impulsivity Assessment Scale - DIAS). Collies were more impulsive on average, consistent with the original purpose of breed selection. Regarding line, working Collies differed from working Labradors, but show lines from the two breeds were not significantly different. Altered or relaxed artificial selection for behavioural traits when appearance rather than behaviour become the primary focus for breeders may reduce average differences in impulsivity between breeds in show lines

Population structure and genetic history of Tibetan Terriers

International audienceAbstractBackgroundTibetan Terrier is a popular medium-sized companion dog breed. According to the history of the breed, the western population of Tibetan Terriers includes two lineages, Lamleh and Luneville. These two lineages derive from a small number of founder animals from the native Tibetan Terrier population, which were brought to Europe in the 1920s. For almost a century, the western population of Tibetan Terriers and the native population in Tibet were reproductively isolated. In this study, we analysed the structure of the western population of Tibetan Terriers, the original native population from Tibet and of different crosses between these two populations. We also examined the genetic relationships of Tibetan Terriers with other dog breeds, especially terriers and some Asian breeds, and the within-breed structure of both Tibetan Terrier populations.ResultsOur analyses were based on high-density single nucleotide polymorphism (SNP) array (Illumina HD Canine 170 K) and microsatellite (18 loci) genotypes of 64 Tibetan Terriers belonging to different populations and lineages. For the comparative analysis, we used 348 publicly available SNP array genotypes of dogs from other breeds. We found that the western population of Tibetan Terriers and the native Tibetan Terriers clustered together with other Asian dog breeds, whereas all other terrier breeds were grouped into a separate group. We were also able to differentiate the western Tibetan Terrier lineages (Lamleh and Luneville) from the native Tibetan Terrier population.ConclusionsOur results reveal the relationships between the western and native populations of Tibetan Terriers and support the hypothesis that Tibetan Terrier belongs to the group of ancient dog breeds of Asian origin, which are close to the ancestors of the modern dog that were involved in the early domestication process. Thus, we were able to reject the initial hypothesis that Tibetan Terriers belong to the group of terrier breeds. The existence of this native population of Tibetan Terriers at its original location represents an exceptional and valuable genetic resource

Understanding hereditary diseases using the dog and human as companion model systems

Animal models are requisite for genetic dissection of, and improved treatment regimens for, human hereditary diseases. While several animals have been used in academic and industrial research, the primary model for dissection of hereditary diseases has been the many strains of the laboratory mouse. However, given its greater (than the mouse) genetic similarity to the human, high number of naturally occurring hereditary diseases, unique population structure, and the availability of the complete genome sequence, the purebred dog has emerged as a powerful model for study of diseases. The major advantage the dog provides is that it is afflicted with approximately 450 hereditary diseases, about half of which have remarkable clinical similarities to corresponding diseases of the human. In addition, humankind has a strong desire to cure diseases of the dog so these two facts make the dog an ideal clinical and genetic model. This review highlights several of these shared hereditary diseases. Specifically, the canine models discussed herein have played important roles in identification of causative genes and/or have been utilized in novel therapeutic approaches of interest to the dog and human