Search

A linear mixed model analysis of elbow and hip score data from UK Labrador retrievers was used to estimate the heritability of elbow score (0.16-0.19) and to determine a moderate and beneficial genetic correlation with hip score (0.40). A small improvement in the genetic trend of elbow score was observed during the years 2000-2008, equivalent to avoiding only the worst 3-4% of scored dogs for breeding, but close to what may have been anticipated if the current British Veterinary Association-approved guidelines were followed. Calculations suggested that a correlated response to indirect selection on hip score may elicit a greater response than direct selection on elbow score and that the genetic trend in elbow score may be explained as a consequence of the stronger selection pressure that has been placed on hip score. Increases in the accuracy of estimated breeding values for elbow score of 4-7% for dogs with elbow data only and 7-11% for dogs with both hip and elbow score were observed from bivariate analysis of elbow and hip data. A selection index confirmed the benefits of bivariate analysis of elbow and hip score data by identifying increases in accuracy (directly related to the response to selection) of 14% from the use of optimum coefficients compared to use of hip data only. The quantified genetic correlation means that hip score effectively acts as a 'secondary indicator' of elbow score in this breed and the preponderance of hip data means that it acts as a major source of information that may be used to improve the accuracy of estimates of genetic risk for elbow dysplasia. [ABSTRACT FROM AUTHOR]

This paper examines the outcomes from recent genetic analyses of hip and elbow scores from British Veterinary Association (BVA)/UK Kennel Club (KC) screening programmes targeted at reducing the prevalence of hip dysplasia (HD) and elbow dysplasia in UK Labrador retrievers. The analyses made use of 25,243 hip scores and 3613 elbow scores. Heritabilities (± standard error) for hip score, analysed on a log scale, and for elbow score were 0.35 ± 0.02 and 0.19 ± 0.04, respectively, with a genetic correlation of 0.41 ± 0.09. For both hip and elbow scores, there was a near perfect genetic correlation between the left and right joint; analysis of hip score showed a predictive benefit of using the total of left and right scores rather than worst score and the benefit of using all component scores rather than their aggregate score. Downward genetic trends were observed in both hip and elbow scores, although the latter was consistent with it being correlated to response to genetic change in hip score. Estimated breeding values (EBVs) offered substantial benefits in accuracy and hence genetic progress when compared to the use of phenotypes for both hip and elbow scores. There are major opportunities for improving selection against elbow dysplasia through the use of bivariate evaluations, although progress against dysplasia would be improved by more widespread elbow scoring. The studies highlighted a number of ways in which data recording for addressing complex traits may be improved in the future. Ongoing advances in genomic technology may be utilised for increasing the rate of genetic progress in selection against HD and for complex diseases in general, through the use of genomic evaluations. [ABSTRACT FROM AUTHOR]

Racehorses competing in short (i.e., ‘sprinters’), middle- or longer-distance (i.e., ‘stayers’) flat races are assumed to have natural variation in locomotion; sprinters having an innately shorter stride than stayers. No study has objectively tested this theory. Here, racehorses (n = 421) were categorised as sprinters, milers or stayers based on known race distance (n = 3269 races). Stride parameters (peak length and frequency) of those racehorses were collected from prior race-pace training sessions on turf (n = 2689; ‘jumpout’, n = 1013), using a locomotion monitoring device. Pedigree information for all 421 racehorses was extracted to three-generations. In training, sprinters had a shorter stride of higher frequency and covered consecutive furlongs faster than stayers (p < 0.001). Relatively short or longer stride did not predict race success, but stayers had greater race success than sprinters (p < 0.001). Peak stride length and frequency were moderately heritable (h2 = 0.15 and 0.20, respectively). In conclusion, differences in stride were apparent between sprinters and stayers (e.g., shorter stride in sprinters) during routine training, even after accounting for their pedigree. Objective data on stride characteristics could supplement other less objectively obtained parameters to benefit trainers in the appropriate selection of races for each individual racehorse.

Small gene effects involved in complex/omnigenic traits remain costly to analyse using current genome-wide association studies (GWAS) because of the number of individuals required to return meaningful association(s), a.k.a. study power. Inspired by field theory in physics, we provide a different method called genomic informational field theory (GIFT). In contrast to GWAS, GIFT assumes that the phenotype is measured precisely enough and/or the number of individuals in the population is too small to permit the creation of categories. To extract information, GIFT uses the information contained in the cumulative sums difference of gene microstates between two configurations: (i) when the individuals are taken at random without information on phenotype values, and (ii) when individuals are ranked as a function of their phenotypic value. The difference in the cumulative sum is then attributed to the emergence of phenotypic fields. We demonstrate that GIFT recovers GWAS, that is, Fisher's theory, when the phenotypic fields are linear (first order). However, unlike GWAS, GIFT demonstrates how the variance of microstate distribution density functions can also be involved in genotype-phenotype associations when the phenotypic fields are quadratic (second order). Using genotype-phenotype simulations based on Fisher's theory as a toy model, we illustrate the application of the method with a small sample size of 1000 individuals., (Creative Commons Attribution license.)

Exercise-induced pulmonary haemorrhage (EIPH) occurs in horses performing high-intensity athletic activity. The application of physics principles to derive a 'physical model', which is coherent with existing physiology and cell biology data, shows that critical parameters for capillary rupture are cell-cell adhesion and cell stiffness (cytoskeleton organisation). Specifically, length of fracture in the capillary is a ratio between the energy involved in cell-cell adhesion and the stiffness of cells suggesting that if the adhesion diminishes and/or that the stiffness of cells increases EIPH is more likely to occur. To identify genes associated with relevant cellular or physiological phenotypes, the physical model was used in a post-genome-wide association study (GWAS) to define gene sets associated with the model parameters. The primary study was a GWAS of EIPH where the phenotype was based on weekly tracheal wash samples collected over a two-year period from 72 horses in a flat race training yard. The EIPH phenotype was determined from cytological analysis of the tracheal wash samples, by scoring for the presence of red blood cells and haemosiderophages. Genotyping was performed using the Illumina Equine SNP50 BeadChip and analysed using linear regression in PLINK. Genes within significant genome regions were selected for sets based on their GeneOntology biological process, and analysed using fastBAT. The gene set analysis showed that genes associated with cell stiffness (cytoskeleton organisation) and blood flow have the most significant impact on EIPH risk., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Many common and relevant diseases affecting equine welfare have yet to be tested regarding structural variants such as copy number variations (CNVs). CNVs make up a substantial proportion of total genetic variability in populations of many species, resulting in more sequence differences between individuals than SNPs. Associations between CNVs and disease phenotypes have been established in several species, but equine CNV studies have been limited. Aim of this study was to identify CNVs and to perform a genome-wide association (GWA) study in Friesian horses to identify genomic loci associated with insect bite hypersensitivity (IBH), a common seasonal allergic dermatitis observed in many horse breeds worldwide., Results: Genotypes were obtained using the Axiom® Equine Genotyping Array containing 670,796 SNPs. After quality control of genotypes, 15,041 CNVs and 5350 CNV regions (CNVRs) were identified in 222 Friesian horses. Coverage of the total genome by CNVRs was 11.2% with 49.2% of CNVRs containing genes. 58.0% of CNVRs were novel (i.e. so far only identified in Friesian horses). A SNP- and CNV-based GWA analysis was performed, where about half of the horses were affected by IBH. The SNP-based analysis showed a highly significant association between the MHC region on ECA20 and IBH in Friesian horses. Associations between the MHC region on ECA20 and IBH were also detected based on the CNV-based analysis. However, CNVs associated with IBH in Friesian horses were not often in close proximity to SNPs identified to be associated with IBH., Conclusions: CNVs were identified in a large sample of the Friesian horse population, thereby contributing to our knowledge on CNVs in horses and facilitating our understanding of the equine genome and its phenotypic expression. A clear association was identified between the MHC region on ECA20 and IBH in Friesian horses based on both SNP- and CNV-based GWA studies. These results imply that MHC contributes to IBH sensitivity in Friesian horses. Although subsequent analyses are needed for verification, nucleotide differences, as well as more complex structural variations like CNVs, seem to contribute to IBH sensitivity. IBH should be considered as a common disease with a complex genomic architecture.

While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions.

The clinical presentation and progression (over 9 months to 13 years) of congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in the Cavalier King Charles spaniel dog are described for six new cases and six previously described cases. Cases presented with a congenitally abnormal (rough/curly) coat and signs of KCS from eyelid opening. Persistent scale along the dorsal spine and flanks with a harsh frizzy and alopecic coat was evident in the first few months of life. Ventral abdominal skin was hyperpigmented and hyperkeratinized in adulthood. Footpads were hyperkeratinized from young adulthood with nail growth abnormalities and intermittent sloughing. Long-term follow-up of cases (13/25) is described. Immunomodulatory/lacrimostimulant treatment had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis. Histopathological analysis of samples (skin/footpads/lacrimal glands/salivary glands) for three new cases was consistent with an ichthyosiform dermatosis, with no pathology of the salivary or lacrimal glands identified histologically. Pedigree analysis suggests the syndrome is inherited by an autosomal recessive mode., (© 2011 American College of Veterinary Ophthalmologists.)

Purpose: To identify causative mutation(s) for congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in Cavalier King Charles spaniel (CKCS) dogs using a candidate gene approach., Methods: DNA samples from 21 cases/parents were collected. Canine candidate genes (CCGs) for similar inherited human diseases were chosen. Twenty-eight candidate genes were identified by searching the Pubmed OMIM database (http://www.ncbi.nlm.nih.gov/omim). Canine orthologues of human candidate genes were identified using the Ensembl orthologue prediction facility (http://www.ensembl.org/index.html). Two microsatellites flanking each candidate gene were selected, and primers to amplify each microsatellite were designed using the Whitehead Institute primer design website (http://frodo.wi.mit.edu/primer3/). The microsatellites associated with all 28 CCGs were genotyped on a panel of 21 DNA samples from CKCS dogs (13 affected and eight carriers). Genotyping data was analyzed to identify markers homozygous in affected dogs and heterozygous in carriers (homozygosity mapping)., Results: None of the microsatellites associated with 25 of the CCGs displayed an association with CKCSID in the 21 DNA samples tested. Three CCGs associated microsatellites were monomorphic across all samples tested., Conclusions: Twenty-five CCGs were excluded as cause of CKCSID. Three CCGs could not be excluded from involvement in the inheritance of CKCSID., (© 2012 American College of Veterinary Ophthalmologists.)

The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML). Of 4143 puppies that met the inclusion criteria, 97.6% had normal hearing status, 2.0% were unilaterally deaf and 0.4% were bilaterally deaf. Heritability of deafness as a trichotomous trait (normal/unilaterally deaf/bilaterally deaf) was estimated at 0.42 using multivariate analysis. Genetic correlations of deafness with iris colour and merle coat colour were 0.58 and 0.26, respectively. These results indicate that there is a significant genetic effect on CSD in Border Collies and that some of the genes determining deafness also influence pigmentation phenotypes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Mixed model analysis of 1252 records of cardiac auscultation of 4- to 5-year-old Cavalier King Charles spaniels (CKCS) from 1991 to 2008 in conjunction with the Kennel Club pedigree records of all dogs registered from the mid 1980s to September 2007 was used to estimate variance parameters of premature mitral valve disease (MVD). Data were limited to dogs ≥4 and <5 years of age to ensure diagnostic distinction between early and late onset MVD. Cardiac murmurs were detected in 108/1252 (8.6%) dogs. Heritability estimates of 0.67 (standard error, SE 0.071) for the grade of murmur and 0.33 (SE 0.072) for the presence/absence of murmur were calculated. The variance due to clinician was 0.02 (SE 0.012) for grade and 0.03 (SE 0.017) for presence/absence of murmur. These results indicate that the presence and severity of MVD, as assessed by cardiac auscultation, in 4- to 5-year-old CKCS is highly heritable and that selection against the disease should be successful., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Mixed model analysis of 384 Cavalier King Charles spaniels (CKCS), with a magnetic resonance imaging diagnosis for the presence or absence of a syrinx, in conjunction with the Kennel Club pedigree records of all dogs registered from the mid 1980s to September 2007, revealed a moderately high estimate of heritability of syringomyelia (h(2)=0.37+/-0.15 standard error) when analysed as a binary trait. Inspection of cases where the disease segregated within families pointed to genes at more than one locus influencing syringomyelia. The availability of estimated breeding values for Kennel Club registered CKCS is a significant step in being able to select against syringomyelia, particularly given the difficulty of ascertaining the disease phenotype., (2009 Elsevier Ltd. All rights reserved.)

Recurrent airway obstruction (RAO) is a multifactorial and polygenic disease. Affected horses are typically 7 years of age or older and show exercise intolerance, increased breathing effort, coughing, airway neutrophilia, mucus accumulation and hyperreactivity as well as cholinergic bronchospasm. The environmental factors responsible are predominantly allergens and irritants in haydust, but the immunological mechanisms underlying RAO are still unclear. Several studies have demonstrated a familiar predisposition for RAO and it is now proven that the disease has a genetic basis. In offspring, the risk of developing RAO is 3-fold increased when one parent is affected and increases to almost 5-fold when both parents have RAO. Segregation analysis in two high-prevalence families demonstrated a high heritability and a complex inheritance with several major genes. A whole genomescan showed chromosome-wide significant linkage of seven chromosomal regions with RAO. Of the microsatellites, which were located near atopy candidate genes, those in a region of chromosome 13 harboring the IL4R gene were strongly associated with the RAO phenotype in the offspring of one RAO-affected stallion. Furthermore, IgE-levels are influenced by hereditary factors in the horse, and we have evidence that RAO-affected offspring of the same stallion have increased levels of specific IgE against moldspore allergens. The identification of genetic markers and ultimately of the responsible genes will not only allow for an improved prophylaxis, i.e. early identification of susceptible individuals and avoidance of high-risk matings, but also improve our ability to find new therapeutic targets and to optimize existing treatments.