Canine Genetics Research Articles

Rising trends in the use of frozen dog sperm: a retrospective study in Belgium and the Netherlands

IntroductionSperm cryopreservation is a valuable technique for storing valuable canine genetics. However, little is known concerning the fate of frozen sperm stored in a sperm bank. This study aimed to characterize dogs presented for sperm cryopreservation and describe the use and popularity of frozen sperm in the Netherlands and Belgium over recent years.MethodsMedical records from dogs presented for sperm cryopreservation between January 1, 2014 and December 31, 2022 at two different freezing centers were reviewed retrospectively. Imported frozen sperm was excluded due to lack of usage information. Each sperm cryopreservation was considered a single event, and data were collected separately for each cryopreserved sample.ResultsA total of 3,090 ejaculates from 1,040 males of 157 different breeds were included and investigated using exploratory data analysis. The findings showed a steady rise in the popularity of sperm cryopreservation, with annual growth rates ranging from 8.4 to 41.9%. The majority of dogs (88.5%) were between 1 and 9 years old at the time of sperm cryopreservation, with nearly one-third aged 2–4 years. Most dogs were collected for sperm cryopreservation once (62.8%) or twice (21.6%). Sperm banks were used for both short- and long-term storage needs, and 6.83% of ejaculates were eventually discarded. The primary use of froze sperm was for international shipment, while 21.8% was used locally for artificial insemination. Depending on the year of cryopreservation, between 44.1 and 79.6% of frozen ejaculates remained unused or only partially used at the time of data collection.DiscussionThe results of this study provides the first comprehensive analysis of the use and popularity of frozen sperm among dog breeders in Belgium and the Netherlands and suggest a change in breeding practices in recent years. The percentage of breeders resorting to sperm cryopreservation and the extent of frozen sperm use in current breeding strategies remain to be defined in future studies.

An Evolutionary Perspective on Dog Behavioral Genetics.

Dogs have played an outsized role in the field of behavioral genetics since its earliest days. Their unique evolutionary history and ubiquity in the modern world make them a potentially powerful model system for discovering how genetic changes lead to changes in behavior. Genomic technology has supercharged this potential by enabling scientists to sequence the DNA of thousands of dogs and test for correlations with behavioral traits. However, fractures in the early history of animal behavior between biological and psychological subfields may be impeding progress. In addition, canine behavioral genetics has included almost exclusively dogs from modern breeds, who represent just a small fraction of all dog diversity. By expanding the scope of dog behavior studies, and incorporating an evolutionary perspective on canine behavioral genetics, we can move beyond associations to understanding the complex interactions between genes and environment that lead to dog behavior.

A map of canine sequence variation relative to a Greenland wolf outgroup.

For over 15years, canine genetics research relied on a reference assembly from a Boxer breed dog named Tasha (i.e., canFam3.1). Recent advances in long-read sequencing and genome assembly have led to the development of numerous high-quality assemblies from diverse canines. These assemblies represent notable improvements in completeness, contiguity, and the representation of gene promoters and gene models. Although genome graph and pan-genome approaches have promise, most genetic analyses in canines rely upon the mapping of Illumina sequencing reads to a single reference. The Dog10K consortium, and others, have generated deep catalogs of genetic variation through an alignment of Illumina sequencing reads to a reference genome obtained from a German Shepherd Dog named Mischka (i.e., canFam4, UU_Cfam_GSD_1.0). However, alignment to a breed-derived genome may introduce bias in genotype calling across samples. Since the use of an outgroup reference genome may remove this effect, we have reprocessed 1929 samples analyzed by the Dog10K consortium using a Greenland wolf (mCanLor1.2) as the reference. We efficiently performed remapping and variant calling using a GPU-implementation of common analysis tools. The resulting call set removes the variability in genetic differences seen across samples and breed relationships revealed by principal component analysis are not affected by the choice of reference genome. Using this sequence data, we inferred the history of population sizes and found that village dog populations experienced a 9-13 fold reduction in historic effective population size relative to wolves.

Dogs and their genes: what ever will they think of next?

The Edward Novitski Prize recognizes creativity and intellectual ingenuity in the solution of problems in genetics research. The prize honors scientific experimental work-either a single experimental accomplishment or a body of work. Ostrander is recognized for work developing the domestic dog as an experimental system for solving fundamental biological problems and identifying genetic sequences of relevance to human health and disease. Including work on disease and behavioral health, Ostrander has shown a dedication to creative methods for understanding canine genetics and the value of translating research organisms to human genetics.

Comparative neurogenetics of dog behavior complements efforts towards human neuropsychiatric genetics.

Domestic dogs display a wide array of heritable behaviors that have intermediate genetic complexity thanks to a long history of human-influenced selection. Comparative genetics in dogs could address the scarcity of non-human neurogenetic systems relevant to human neuropsychiatric disorders, which are characterized by mental, emotional, and behavioral symptoms and involve vastly complex genetic and non-genetic risk factors. Our review describes the diverse behavioral "phenome" of domestic dogs, past and ongoing sources of behavioral selection, and the state of canine behavioral genetics. We highlight two naturally disordered behavioral domains that illustrate how dogs may prove useful as a comparative, forward neurogenetic system: canine age-related cognitive dysfunction, which can be examined more rapidly given the attenuated lifespan of dogs, and compulsive disorders, which may have genetic roots in purpose-bred behaviors. Growing community science initiatives aimed at the companion dog population will be well suited to investigating such complex behavioral phenotypes and offer a comparative resource that parallels human genomic initiatives in scale and dimensionality.

Identification of Genetic Risk Factors for Monogenic and Complex Canine Diseases.

Advances in DNA sequencing and other technologies have greatly facilitated the identification of genetic risk factors for inherited diseases in dogs. We review recent technological developments based on selected examples from canine disease genetics. The identification of disease-causing variants in dogs with monogenic diseases may become a widely employed diagnostic approach in clinical veterinary medicine in the not-too-distant future. Diseases with complex modes of inheritance continue to pose challenges to researchers but have also become much more tangible than in the past. In addition to strategies for identifying genetic risk factors, we provide some thoughts on the interpretation of sequence variants that are largely inspired by developments in human clinical genetics.

Challenging stereotypes improves understanding of canine behavioral genetics.

A recent study by Morrill et al. (2022) highlights important connections between genetics and behavior in domestic dogs (Canis familiaris), while also contesting the idea that common breed stereotypes accurately predict individual dog behavior. These findings challenge scientists and dog professionals to deepen our understanding of dog behavior, moving past generalizations and toward approaches that better account for the behavior of individuals.

Canine coat pigmentation genetics: a review.

Our understanding of canine coat colour genetics and the associated health implications is developing rapidly. To date, there are 15 genes with known roles in canine coat colour phenotypes. Many coat phenotypes result from complex and/or epistatic genetic interactions among variants within and between loci, some of which remain unidentified. Some genes involved in canine pigmentation have been linked to aural, visual and neurological impairments. Consequently, coat pigmentation in the domestic dog retains considerable ethical and economic interest. In this paper we discuss coat colour phenotypes in the domestic dog, the genes and variants responsible for these phenotypes and any proven coat colour-associated health effects.

Improving the resolution of canine genome-wide association studies using genotype imputation: A study of two breeds.

SummaryGenotype imputation using a reference panel that combines high-density array data and publicly available whole genome sequence consortium variant data is potentially a cost-effective method to increase the density of extant lower-density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed-specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R2 = 0.94) and the highest for the Italian Spinone dataset (mean R2 = 0.97). This study’s findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed-specific array data and multi-breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed-specific data, is described in detail to facilitate and encourage use of this technique in canine genetics.

Dog10K_Boxer_Tasha_1.0: A Long-Read Assembly of the Dog Reference Genome.

The domestic dog has evolved to be an important biomedical model for studies regarding the genetic basis of disease, morphology and behavior. Genetic studies in the dog have relied on a draft reference genome of a purebred female boxer dog named “Tasha” initially published in 2005. Derived from a Sanger whole genome shotgun sequencing approach coupled with limited clone-based sequencing, the initial assembly and subsequent updates have served as the predominant resource for canine genetics for 15 years. While the initial assembly produced a good-quality draft, as with all assemblies produced at the time, it contained gaps, assembly errors and missing sequences, particularly in GC-rich regions, which are found at many promoters and in the first exons of protein-coding genes. Here, we present Dog10K_Boxer_Tasha_1.0, an improved chromosome-level highly contiguous genome assembly of Tasha created with long-read technologies that increases sequence contiguity >100-fold, closes >23,000 gaps of the CanFam3.1 reference assembly and improves gene annotation by identifying >1200 new protein-coding transcripts. The assembly and annotation are available at NCBI under the accession GCF_000002285.5.

Prevalence, geographic distribution, and impact on lifespan of a dilated cardiomyopathy-associated RNA-binding motif protein 20 variant in genotyped dogs

IntroductionThe study objectives were to determine the prevalence and geographic distribution of a dilated cardiomyopathy (DCM)-associated RNA-binding motif protein 20 (RBM20) variant in canine DNA samples submitted for testing and to evaluate the influence of the genotype on cardiac phenotype and lifespan. AnimalsSamples from 2136 dogs including 1834 Standard Schnauzers (SSNZ), 266 Giant Schnauzers (GSNZ), and 36 dogs of other breeds. MethodsThe University of Missouri Canine Genetics Laboratory's sample-accession spreadsheet and Orthopedic Foundation for Animals' database were retrospectively reviewed for samples submitted for RBM20 genotyping from November, 2013, through May, 2018. Data analyzed included breed, date of birth, RBM20 genotype (homozygous wild-type, heterozygous variant [HET], or homozygous variant [HOM]), geographic origin of submission, pedigree, cardiac phenotype, and date of death or current age if alive. Results and DiscussionThe RBM20 variant was only detected in SSNZ and GSNZ. A total of 389 SSNZ were variant-positive (prevalence = 21.2%), with 361 HET (19.7%) and 28 HOM (1.5%). Of the HOM SSNZ, DCM was confirmed in 26 of 28 (92.9%), with the remainder lost to follow-up. The median lifespan of HOM SSNZ (3.06 years) was significantly shorter than that for HET (15.11 years) and wild-type (15.18 years) SSNZ. Twenty-six GSNZ were variant-positive (prevalence = 9.8%), with 23 HET (8.6%) and three HOM (1.1%). Nine GSNZ belonged to one family, including the three HOM GSNZ that all had DCM. ConclusionsThe HOM genotype is associated with DCM and premature death in SSNZ and GSNZ.

Expanding the genetic toolbox

Knowledge of canine genetics has advanced rapidly in recent years. Researchers say even deeper understanding is ahead, and that it could support a shift to more preventative veterinary care. But...

Selected canine abstracts from the Companion Animal Genetic Health conference 2018 (CAGH 2018): Canine Genetics and Epidemiology

Selected canine abstracts from the Companion Animal Genetic Health conference 2018 (CAGH 2018): Canine Genetics and Epidemiology

Genetic diversity of Barbary lion based on genealogic analysis

Genetic diversity of Barbary lion based on genealogic analysis

Give a Dog a Genome

A group of researchers are constructing a precision tool that will be used to shape the future health of the UK dog population. That team is made up of geneticists rather than engineers, and the technology they are developing will help them identify the genes responsible for inherited diseases in pedigree breeds. Dr Cathryn Mellersh, head of canine genetics at the Animal Health Trust, told John Bonner how it works.

Canine Behaviour and Genetics: Special issue on the London, 2015 meetings

Canine Behaviour and Genetics: Special issue on the London, 2015 meetings

Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders.

BackgroundThe 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.ResultsTo 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.ConclusionsThese 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 First Canine Behavior and Genetics Conference: Summary and recommendations for future directions in canine behavioral science

Abstract This paper is a narrative descriptive review of the oral presentations from the first Canine Behavior and Genetics Conference and is a synthesis of the general themes from these messages to generate key conclusions on future directions for canine behavior science. The conference was set in London in June 2015 and had 91 attendees from 10 countries. There were 17 oral presentations supported by a poster schedule with 16 posters. Two rapporteurs were invited to attend the conference and to give their conclusions on routes forward for Canine Behavioral Science. The oral presentations covered diverse topics including behavioral genetics and genomics, phenotype assessment, neurobiology and sensory biology, evolution, and socialization. The rapporteurs concluded from these presentations that global consensus on standardized systems for behavioral nomenclature (definitions) and behavioral measurement were required for the improvement of scientific output from canine behavioral research. A multidisciplinary research model and the use of linked databases were also deemed critical for effective advancement of canine behavioral science. The first Canine Behavior and Genetics Conference acted as an incubator for many nascent ideas and collaborations in canine behavioral science. The coming years will judge whether these eggs hatch and generate real welfare improvements for dogs and increased respect of the dog as both a valued working animal and a model of important translational diseases worldwide.

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.

Canine Models for Copper Homeostasis Disorders.

Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.