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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.

Direct-to-consumer canine genetic testing is becoming increasingly popular among dog owners. The data collected therein provides intriguing insight into the current status of morphological variation present within purebred populations. Mars WISDOM PANELTM data from 11,790 anonymized dogs, representing 212 breeds and 4 wild canine species, were evaluated at genes associated with 7 coat color traits and 5 physical characteristics. Frequencies for all tested alleles at these 12 genes were determined by breed and by phylogenetic grouping. A sub-set of the data, consisting of 30 breeds, was divided into separate same-breed populations based on country of collection, body size, coat variation, or lineages selected for working or conformation traits. Significantly different (p ≤ 0.00167) allele frequencies were observed between populations for at least one of the tested genes in 26 of the 30 breeds. Next, standard breed descriptions from major American and international registries were used to determine colors and tail lengths (e.g. genetic bobtail) accepted within each breed. Alleles capable of producing traits incongruous with breed descriptions were observed in 143 breeds, such that random mating within breeds has probabilities of between 4.9e-7 and 0.25 of creating undesirable phenotypes. Finally, the presence of rare alleles within breeds, such as those for the recessive black coloration and natural bobtail, was combined with previously published identity-by-decent haplotype sharing levels to propose pathways by which the alleles may have spread throughout dog breeds. Taken together, this work demonstrates that: 1) the occurrence of low frequency alleles within breeds can reveal the influence of regional or functional selection practices; 2) it is possible to visualize the potential historic connections between breeds that share rare alleles; and 3) the necessity of addressing conflicting ideals in breed descriptions relative to actual genetic potential is crucial.

Genetic testing for dogs is big business. It is too easy for companies to sell false hope, warn Lisa Moses, Steve Niemi and Elinor Karlsson. They call for regulation. Genetic testing for dogs is big business. It is too easy for companies to sell false hope, warn Lisa Moses, Steve Niemi and Elinor Karlsson. They call for regulation.

Abstract Background Clinical signs and their progression in Beagles with Lafora disease are poorly described. Objectives To describe clinical signs in Beagles with Lafora disease. Animals Twenty-eight Beagles with Lafora disease confirmed by genetic testing or histopathology. Methods Retrospective multicenter case series. Data regarding signalment, clinical signs, diagnostic tests and treatment were retrieved from hospital data files. A questionnaire was sent to owners asking about neurological deficits, changes in cognitive functions, behavioral changes, response to treatment and survival time. Results Onset of clinical signs was 8.3 years (mean; range, 6.3-13.3). All dogs had myoclonic episodes as an initial clinical sign with tonic-clonic seizures in n = 11/28 (39%) and n = 12/28 (43%) later developing tonic-clonic seizures. Deficits of coordination (n = 21/25; 84%), impaired vision (n = 15/26; 58%), and impaired hearing (n = 13/26; 50%) developed later. Mental decline was observed as loss of house training (urination; n = 8/25; 32%), difficulties performing learned tasks (n = 9/25; 36%), and difficulties learning new tasks (n = 7/23; 30%). Common behavioral changes were: increased photosensitivity (n = 20/26; 77%), staring into space (n = 16/25; 64%), reduced stress resistance (n = 15/26; 58%), increased noise sensitivity (n = 14/26; 54%), and separation anxiety (n = 11/25; 44%). Twenty-one dogs were alive (median age 11.9 years; range, 9.8-18.6), and 7 dogs were dead (mean age 12.1 years; SD: 1.3; range, 10.5-12.6) at time of writing. Conclusions and Clinical Importance Lafora disease in Beagles causes significant behavioral changes, and mental decline as well as neurological deficits in addition to myoclonic episodes and generalized tonic-clonic seizures. Nevertheless, a relatively normal life span can be expected.

In southern European countries, multicentric lymphoma and leishmaniosis are the main differential diagnoses in dogs presented with generalized lymphadenomegaly. The cytological examination is in some cases inconclusive and polymerase chain reaction (PCR) for antigen receptor rearrangement (PARR) has become a common method to confirm or rule out a lymphoproliferative neoplasia. According to the literature, leishmaniosis may lead to clonal arrangements and therefore to a false diagnosis of lymphoma, but this assumption is made from a single leishmania infected dog. Therefore, the objective of this study was to prospectively evaluate results from PARR in dogs with lymphadenomegaly due to clinical leishmaniosis at the moment of diagnosis. 31 dogs with a diagnosis of leishmaniosis based on the LeishVet guidelines were included in the study. Samples from enlarged lymph nodes were taken for cytological examination, clonality testing and Leishmania infantum PCR. All 31 dogs had medium to high positive antibody titers against Leishmania spp. and 30/31 had a positive Leishmania PCR from the lymph node. A polyclonal arrangement for B cells (immunoglobulin heavy chain gene) and T cells (T-cell receptor gamma chain gene) antigen receptors was found in 28/31 dogs. Two out of 31 dogs showed a monoclonal arrangement for Ig with high (1:2) and low (1:7) polyclonal background respectively; and one of the 31 dogs showed a monoclonal arrangement for T cell receptor with low (1:3) polyclonal background. Infections with Leishmania infantum resulted in clonal rearrangement, and therefore in a possible false diagnosis of lymphoma, in 3 out of 31 dogs (9.7%). Although, PARR is a useful method to differentiate lymphoma from reactive lymphoid hyperplasia in dogs with leishmaniosis, mono-/biclonal results should be interpreted carefully, especially in the presence of any degree of polyclonal background, and together with other clinicopathological findings.

Abstract Background Immune-mediated myositis (IMM) in American Quarter Horses (QHs) causes acute muscle atrophy and lymphocytic infiltration of myofibers. Recently, an E321G mutation in a highly conserved region of the myosin heavy chain 1 (MYH1) gene was associated with susceptibility to IMM and nonexertional rhabdomyolysis. Objectives To estimate prevalence of the E321G MYH1 variant in the QH breed and performance subgroups. Animals Three-hundred seven elite performance QHs and 146 random registered QH controls. Methods Prospective genetic survey. Elite QHs from barrel racing, cutting, halter, racing, reining, Western Pleasure, and working cow disciplines and randomly selected registered QHs were genotyped for the E321G MYH1 variant and allele frequencies were calculated. Results The E321G MYH1 variant allele frequency was 0.034 ± 0.011 in the general QH population (6.8% of individuals in the breed) and the highest among the reining (0.135 ± 0.040; 24.3% of reiners), working cow (0.085 ± 0.031), and halter (0.080 ± 0.027) performance subgroups. The E321G MYH1 variant was present in cutting (0.044 ± 0.022) and Western Pleasure (0.021 ± 0.015) QHs at lower frequency and was not observed in barrel racing or racing QHs. Conclusions and Clinical Importance Knowing that reining and working cow QHs have the highest prevalence of the E321G MYH1 variant and that the variant is more prevalent than the alleles for hereditary equine regional dermal asthenia and hyperkalemic periodic paralysis in the general QH population will guide the use of genetic testing for diagnostic and breeding purposes.

Background This study aimed at (1) comparing the accuracies of genomic prediction for parasite resistance in sheep based on whole-genome sequence (WGS) data to those based on 50k and high-density (HD) single nucleotide polymorphism (SNP) panels; (2) investigating whether the use of variants within quantitative trait loci (QTL) regions that were selected from regional heritability mapping (RHM) in an independent dataset improved the accuracy more than variants selected from genome-wide association studies (GWAS); and (3) comparing the prediction accuracies between variants selected from WGS data to variants selected from the HD SNP panel. Results The accuracy of genomic prediction improved marginally from 0.16 ± 0.02 and 0.18 ± 0.01 when using all the variants from 50k and HD genotypes, respectively, to 0.19 ± 0.01 when using all the variants from WGS data. Fitting a GRM from the selected variants alongside a GRM from the 50k SNP genotypes improved the prediction accuracy substantially compared to fitting the 50k SNP genotypes alone. The gain in prediction accuracy was slightly more pronounced when variants were selected from WGS data compared to when variants were selected from the HD panel. When sequence variants that passed the GWAS - l o g 10 ( p v a l u e ) threshold of 3 across the entire genome were selected, the prediction accuracy improved by 5% (up to 0.21 ± 0.01), whereas when selection was limited to sequence variants that passed the same GWAS - l o g 10 ( p v a l u e ) threshold of 3 in regions identified by RHM, the accuracy improved by 9% (up to 0.25 ± 0.01). Conclusions Our results show that through careful selection of sequence variants from the QTL regions, the accuracy of genomic prediction for parasite resistance in sheep can be improved. These findings have important implications for genomic prediction in sheep.

The Cleveland Bay horse is one of the oldest equines in the United Kingdom, with pedigree data going back almost 300 years. The studbook is essentially closed and because of this, there are concerns about loss of genetic variation across generations. The breed is one of five equine breeds listed as \"critical\" (<300 registered adult breeding females) by the UK Rare Breeds Survival Trust in their annual Watchlist. Due to their critically endangered status, the current breadth of their genetic diversity is of concern, and assessment of this can lead to improved breed management strategies. Herein, both genealogical and molecular methods are combined in order to assess founder representation, lineage, and allelic diversity. Data from 15 microsatellite loci from a reference population of 402 individuals determined a loss of 91% and 48% of stallion and dam lines, respectively. Only 3 ancestors determine 50% of the genome in the living population, with 70% of maternal lineage being derived from 3 founder females, and all paternal lineages traced back to a single founder stallion. Methods and theory are described in detail in order to demonstrate the scope of this analysis for wider conservation strategies. We quantitatively demonstrate the critical nature of the genetic resources within the breed and offer a perspective on implementing this data in considered breed management strategies.

DNA testing for autosomal recessive disease mutations in many dog breeds is now relatively commonplace. There have, however, been few efforts made to determine changes in the frequency of disease causing mutations as a result of probable selection based on the results of DNA testing. This study makes use of genotype data from both DNA test results reported to the UK Kennel Club and where known from a 'hereditary status' (where a definitive genotype may be inferred and ascribed based on known parental genotypes) to do so. The results, using all known genotype data, show a general and sizeable decline in disease causing mutation frequency across eight diseases in eight breeds (by between 12-86% in dogs born 2-4 years after publication of the mutation, and by nearly 90% or more in those born 8-10 years after). In contrast, data from test results only, while revealing an almost complete and immediate end to the production of affected individuals, show little general decline in either the derived mutation frequency or the proportion of heterozygote carriers. It appears that the numerical size of the breed is an important determinant on the rate of uptake of a DNA test (as judged by the proportion of a breed born four years after publication of the disease-causing mutation with a known genotype). These results show that dog breeders appear to be incorporating the results of DNA testing into their selection strategies to successfully decrease the frequency of the mutation. It is shown that use of DNA test result data alone does not reveal such trends, possibly as some breeders undertake testing to determine clear stock which can then be used to produce future disease-free generations in the knowledge they are not carrying the disease causing mutation.

Canine hip dysplasia is a common, non-congenital, complex and hereditary disorder. It can inflict severe pain via secondary osteoarthritis and lead to euthanasia. An analogous disorder exists in humans. The genetic background of hip dysplasia in both species has remained ambiguous despite rigorous studies. We aimed to investigate the genetic causes of this disorder in one of the high-risk breeds, the German Shepherd. We performed genetic analyses with carefully phenotyped case-control cohorts comprising 525 German Shepherds. In our genome-wide association studies we identified four suggestive loci on chromosomes 1 and 9. Targeted resequencing of the two loci on chromosome 9 from 24 affected and 24 control German Shepherds revealed deletions of variable sizes in a putative enhancer element of the NOG gene. NOG encodes for noggin, a well-described bone morphogenetic protein inhibitor affecting multiple developmental processes, including joint development. The deletion was associated with the healthy controls and mildly dysplastic dogs suggesting a protective role against canine hip dysplasia. Two enhancer variants displayed a decreased activity in a dual luciferase reporter assay. Our study identifies novel loci and candidate genes for canine hip dysplasia, with potential regulatory variants in the NOG gene. Further research is warranted to elucidate how the identified variants affect the expression of noggin in canine hips, and what the potential effects of the other identified loci are.