Determining the heritable component of dairy cattle foot lesions.

Lameness and hoof health affect dairy cows as an animal welfare issue, in decreased milk production, and in premature culling. Selection schemes for dairy cattle focus on sire contribution to milk production, with little consideration of the cow's physical structure or disease probability. On 3 commercial California dairies, 6 phenotypic binary hoof traits that contribute to lameness were recorded: white line disease, sole ulcer, other claw horn lesions, foot rot (interdigital phlegmon), foot warts (digital dermatitis), and other lesions. Monthly lactation records were collected from December 2006 to April 2009 with weekly observations of hoof lesions for lame and dry cows. In addition to hoof lesion information, data on cows (n=5,043) included parentage, birth date, freshening date, lactation number, and date of lameness diagnosis. The prevalence of hoof lesions ranged from a low of 2.2% (foot rot) to a high of 17.1% (foot warts). The farm environment increased the odds ratio depending upon the lesion. Lameness was more common in early lactation and as lactation number increased. Using a threshold model, heritabilities and repeatabilities were estimated for each binary trait. The heritability for risk varied by lesion, with the higher estimates being 0.40 (95% confidence interval: 0.20-0.67) for digital dermatitis and 0.30 (95% confidence interval: 0.08-0.63) for sole ulcer. Including terms to account for cow productivity on either a 305-d mature-equivalent basis or a per-lactation basis had minimal effect on the heritability estimates, suggesting that selection for hoof health is not correlated with response to selection for greater milk production and that improvement could be made for both traits. The genetic component lends support for further genetic studies to identify loci contributing to some of the lesion phenotypes such as foot warts or sole ulcers, 2 of the top 3 causes of lameness in dairy cattle.

Folic acid supplementation does not decrease stillbirths and congenital malformations in a guide dog colony.

OBJECTIVES: To investigate if maternal folic acid supplementation (5 mg) is associated with a reduction of cleft palates, umbilical hernias, stillbirths and caesarean sections in a guide dog breeding colony. MATERIALS AND METHODS: Labrador retrievers, golden retrievers and Labrador/golden Crosses from the breeding colony of a professional guide dog training organisation were eligible for inclusion. Dams in the treatment group (n = 137) received 5 mg oral folic acid supplementation daily from the start of pro-oestrous through day 40 of gestation. A historical control group (n = 134) was selected from the previous calendar year for comparison. A logistic regression model identified the relative risk of disease (cleft palates, umbilical hernias, stillbirths and caesarean sections) for puppies whose dams did or did not receive folic acid supplementation. RESULTS: A total of 1917 puppies (890 control, 1027 treatment; from 294 litters) were produced during the entire study period, with 994 puppies (494 control, 500 treatment; from 144 litters) born to the subset of dams (n = 72) who produced litters during both the control and treatment periods. All 95% highest posterior densities of relative risk included 1.0, failing to detect differences between the treatment and control groups on incidence rate of cleft palate (control: 2.25%; treatment: 2.34%), umbilical hernias (control: 1.91%; treatment: 3.12%), stillbirths (control: 3.26%; treatment: 2.92%) and caesarean sections (control: 1.45%; treatment: 1.28%). CLINICAL SIGNIFICANCE: There was no observable reduction of cleft palate, umbilical hernia, stillbirth or caesarean section associated with folic acid supplementation during pregnancy in the study colony. For a domestic dog cohort with a low tendency of hereditary malformations, such as this study colony, 5 mg dietary folic acid supplementation should not be expected to drastically improve or eradicate these diseases.

Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis.

Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.

A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for ocular squamous cell carcinoma in Belgian horses.

BACKGROUND: Belgian horses are commonly affected with ocular squamous cell carcinoma (SCC), the most common cancer of the equine eye. A missense mutation in damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) has been established as a recessive genetic risk factor for ocular SCC in the Haflinger breed. A sample of Belgian horses with unknown SCC phenotype was shown to possess this variant at a similar frequency to the Haflinger breed. Retrospective studies indicate that chestnut coat colour may predispose to the development of SCC. OBJECTIVES: To determine if DDB2 c.1013C>T is a risk factor for ocular SCC in a strictly phenotyped sample of Belgian horses. To investigate associations between coat colour loci genotypes and ocular SCC. STUDY DESIGN: Retrospective and prospective case identification, genetic investigation. METHODS: Genomic DNA was isolated from blood, hair or formalin-fixed paraffin-embedded tissue from 25 Belgian horses with histologically confirmed ocular SCC and 18 unaffected Belgian horses. Association testing of 34 single nucleotide variants from 11 genomic loci and genotyping for DDB2 c.1013C>T and coat colour alleles were performed. Exons of DDB2 were sequenced in four cases and two controls. Associations were analysed by Chi-square or Fisher's exact tests and relative risk was calculated. RESULTS: Homozygosity for DDB2 c.1013C>T was significantly associated with ocular SCC (P = 7.4 × 10-7 ). Seventy-six per cent of affected horses were homozygous for the variant. Relative risk for homozygous horses developing SCC was 4.0 (P = 1.0 × 10-4 ). Sequencing DDB2 did not identify a variant more concordant with disease phenotype. An association between disease and coat colour loci was not identified. MAIN LIMITATIONS: Phenotyping was determined at a single timepoint. Each included horse genotyped as chestnut, so association with this MC1R variant could not be investigated. CONCLUSIONS: A missense variant, DDB2 c.1013C>T, p.Thr338Met, is a risk factor for ocular SCC in Belgian horses. A genetic risk test is commercially available.

Influence of genetic architecture on contemporary local evolution in the soapberry bug, Jadera haematoloma: artificial selection on beak length.

Little is known about the influence of genetic architecture on local adaptation. We investigated the genetic architecture of the rapid contemporary evolution of mouthparts, the flight polymorphism and life history traits in the soapberry bug Jadera haematoloma (Hemiptera) using laboratory selection. The mouthparts of these seed-feeding bugs have adapted in 40-50 years by decreasing in length following novel natural selection induced by a host switch to the seeds of an introduced tree with smaller fruits than those of the native host vine. Laboratory selection on beak length in both an ancestral population feeding on the native host and a derived population feeding on the introduced host reveals genetic variance allowing a rapid response (heritabilities of 0.51-0.87) to selection for either longer or shorter beaks. This selection resulted in reverse evolution by restoring long beaks in the derived population and forward evolution by re-creating short beaks in the ancestral bugs. There were strong genetic correlations (0.68-0.84) in both populations between beak lengths and the frequency of flight morphs, with short beaks associated with short wings. The results reveal a genetically interrelated set of adaptive multivariate traits including both beak length and flight morph. This suite of traits reflects host plant patchiness and seeding phenology. Weaker evidence suggests that egg mass and early egg production may be elements of the same suite. Reversible or forward evolution thus may occur in a broad set of genetically correlated multivariate traits undergoing rapid contemporary adaptation to altered local environments.

Maternal omega-3 polyunsaturated fatty acid supplementation on offspring hip joint conformation.

Unsaturated omega-3 fatty acids, especially docosahexaenoic acid (DHA), when fed to dogs improves cognitive and neurological development. Supplementation with omega-3 fatty acids such as DHA and eicosapentaenoic acid (EPA) has also been associated with lipid peroxidation, which in turn has been implicated in reduced body weight and altered bone formation. To assess the impact of omega-3 fatty acid supplementation on skeletal growth, diets containing three levels of DHA and EPA (0.01 and 0.01%, 0.14 and 0.12%, and 0.21 and 0.18%, respectively) were fed to bitches during gestation and lactation with puppies also supplemented through weaning. Thus, the subjects studied were the puppies supplemented with DHA and EPA through gestation and early postnatal life. The hip joint conformation of the puppies (n = 676) was recorded at adulthood using two radiographic, non-invasive evaluations. In this population, females had higher hip distraction indices (DI) than males. Males from the lower two levels of DHA and EPA supplementation had significantly smaller hip DI than all females and males from the highest DHA and EPA supplementation. In contrast, there were no diet effects on anatomical indicators of hip joint conformation and no visible arthritic changes. These data suggest that dietary supplementation of DHA and EPA during gestation and the perinatal period to weaning does not adversely influence hip joint formation of dogs.

Long-term genetic selection reduced prevalence of hip and elbow dysplasia in 60 dog breeds.

Canine hip dysplasia (CHD) and elbow dysplasia (ED) impact the health and welfare of all dogs. The first formally organized assessment scheme to improve canine health centered on reducing the prevalence of these orthopedic disorders. Phenotypic screening of joint conformation remains the currently available strategy for breeders to make selection decisions. The present study evaluated the efficacy of employing phenotypic selection on breed improvement of hips and elbows using the Orthopedic Foundation for Animals complete database spanning the 1970-2015 time period. Sixty breeds having more than 1000 unique hip evaluations and 500 elbow evaluations (1,056,852 and 275,129 hip and elbow records, respectively) were interrogated to derive phenotypic improvement, sex and age at time of assessment effects, correlation between the two joints, heritability estimates, estimated breeding values (EBV), and effectiveness of maternal/paternal selection. The data demonstrated that there has been overall improvement in hip and elbow conformation with a reduction in EBV for disease liability, although the breeds differed in the magnitude of the response to selection. Heritabilities also differed substantially across the breeds as did the correlation of the joints; in the absence of a universal association of these differences with breed size, popularity, or participation in screening, it appears that the breeds themselves vary in genetic control. There was subtle, though again breed specific, impact of sex and older ages on CHD and ED. There was greater paternal impact on a reduction of CHD. In the absence of direct genetic tests for either of these two diseases, phenotypic selection has proven to be effective. Furthermore, the data underscore that selection schemes must be breed specific and that it is likely the genetic profiles will be unique across the breeds for these two conditions. Despite the advances achieved with phenotypic selection, incorporation of EBVs into selection schemes should accelerate advances in hip and elbow improvement.

Cardiac adaptations in SCNT newborn cloned calves during the first month of life assessed by echocardiography.

The aim of this study was to compare cardiac morphology in newborn and month-old control and cloned calves. A total of 10 in vivo-derived (IVD) control (five Holstein, five Hereford) and seven cloned (five Holstein, two Hereford) calves were subjected to echocardiographic examination, including 2D, M-mode, spectral and color flow Doppler evaluation at Day 1 (mean 26.3 h) and Day 30 (mean 29.2 days) after birth. Echocardiographic measurements were compared between control and cloned calves, and between Hereford and Holstein control calves of the same age. At Day 1 and at Day 30 after birth, left ventricular free wall (LVFW) and interventricular septal (IVS) thicknesses were greater in Holstein calves than Hereford calves. Several indices of myocardial wall thickness were increased in cloned versus control calves at Day 1 after birth, and included systolic LVFW thickness, systolic right ventricular free wall (RVFW) thickness, diastolic LVFW thickness, diastolic RVFW thickness and diastolic IVS thickness (p < 0.05). Differences between cloned and non-cloned calves were no longer evident at Day 30 after birth. The apparent disappearance of the cloning effect on cardiac structures may reflect the influence of placenta on fetal cardiac morphology, suggestive of a placental hemodynamic role in fetal cardiac muscle development. Differences seen in clones at birth spontaneously resolved by Day 30 of age, after organ development recovery from cardiovascular abnormalities of presumed placental origin. Echocardiographic measurements should provide useful data for research and clinical evaluation of high-risk neonatal calves of both breeds and from clones of the same breed.

Genetic evaluation of Addison's disease in the Portuguese Water Dog.

BACKGROUND: Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. RESULTS: The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (+/- 0.16); there were no differences in risk for disease across sexes (p > 0.49). Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. CONCLUSION: The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.

Heritability and segregation analysis of deafness in U.S. Dalmatians.

Hereditary loss of hearing affects many breeds of the domestic dog, but the Dalmatian has the highest prevalence. Approximately 30% are affected in the United States (U.S.) population. It is widely accepted that a relationship exists between deafness and pigmentation in the dog and also in other animals. While the Dalmatian exemplifies this relationship, the genetic origin and mode of inheritance of deafness in this breed are unknown. The goals of this study were to: (1) estimate the heritability of deafness in an extended kindred of U.S. Dalmatians and (2) determine, through complex segregation analysis, whether there is a major segregating locus that has a large effect on the expression of deafness. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 considering it as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a single major gene affecting the disorder is not persuasive.

Spatial distribution of growth hormone receptor, insulin-like growth factor-I receptor and apoptotic chondrocytes during growth plate development.

Linear bone growth depends upon proliferation, maturation, and apoptosis of growth plate chondrocytes, processes regulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I). To investigate the contribution of GH, IGF-I and apoptosis to growth plate function, the expression of GH receptor (GHR) and IGF-I receptor (IGF-IR) mRNA were evaluated by in situ hybridization in fractionated costochondral growth plates of growing rats (at 2, 4, and 7 weeks). Apoptosis was determined by TUNEL assay and morphology in histological sections. GHR mRNA was greatest in resting cells with hypertropic cells increasing GHR expression with increasing age. Hypertropic and resting cell IGF-IR mRNA declined over the ages studied. Receptor mRNA expression was altered by exposing cells to GH or IGF-I. GH and IGF significantly decreased GHR mRNA in proliferative cells. GH and IGF also decreased IGF-IR mRNA in resting cells and the 2- and 4-week-old proliferative and hypertropic cells. Treating cells in culture with GH increased the number of apoptotic cells across all ages and zones. Histologically, apoptotic cells were observed at the chondro-osseous junction and within actively proliferating chondrocytes but not in resting cells. Apoptosis was highest at 4 weeks of age with lateral regions displaying the greatest number of cells undergoing apoptosis. These data indicate that apoptosis plays a role in growth plate function, particularly spatial configuration as indicated by the preferential lateral cell apoptosis. The susceptibility of proliferative cells to GHR and IGF-IR down regulation during the period of greatest apoptosis supports a role for the GH-IGF axis in both proliferation and apoptosis during growth plate development.

Partitioning of feed intake into maintenance and gain in growing beef cattle: Evaluation of conventional and Bayesian analyses.

The robustness of efficiency estimates depends on theoretical consistency of models from which those estimates are developed; functional forms of the variables must be globally consistent with theoretical properties regarding feed utilization for maintenance and gain in growing and finishing cattle. Model parameter estimates and their dimensions must be unique or estimates of feed utilization and gain will not reflect reality. A linear equation commonly used to estimate daily DMI by the th individual animal (ADFI), based on mean weight and gain during a feeding period, was evaluated to determine if that model was correctly specified and if the vector predicted ADFI differed from the vector observed ADFI. Three independently gathered data sets were evaluated using a multiple linear regression model; variability described by that model failed to capture observed variability in the data (lack of fit, < 0.10), and predicted ADFI differed from observed ( < 0.05); for 1 of the 3 data sets, residuals were not normally distributed ( < 0.001). Functional forms of the variables in the first model evaluated, characterizing ADFI required for maintenance ( × BW) and gain ( × ADG), were consistent with neither published empirical nor theoretical relationships among ADFI, BW, and ADG. Parameter estimates determined for that linear model were not BLUE. Better fits among final BW, initial BW, and ADFI were found for a first-order relationship, in which final BW was a function of initial BW and ADFI, as indicated by > 0.90. The linear model and, to a lesser degree, the first nonlinear model lacked theoretical and global consistency. A second nonlinear model, which described retained energy as a function of ME intake, best fit the data, and functional forms of variables describing ME intake at maintenance and the efficiency of ME utilization for gain were consistent with theoretical estimates found in the literature. Changes in feed intake and live BW in linear and nonlinear models failed to adequately describe efficiencies of metabolic processes, which are better characterized by changes in retained energy as a function of ME intake in nonlinear models.

Ten inherited disorders in purebred dogs by functional breed groupings.

BACKGROUND: Analysis of 88,635 dogs seen at the University of California, Davis Veterinary Medical Teaching Hospital from 1995 to 2010 identified ten inherited conditions having greater prevalence within the purebred dog population as compared to the mixed-breed dog population: aortic stenosis, atopy/allergic dermatitis, gastric dilatation volvulus (GDV), early onset cataracts, dilated cardiomyopathy, elbow dysplasia, epilepsy, hypothyroidism, intervertebral disk disease (IVDD), and hepatic portosystemic shunt. The objective of the present study was to ascertain if disorders with higher prevalence in purebreds were restricted to particular breed group classifications within the purebred population, specifically the American Kennel Club breed grouping or groups with genomic similarities based upon allele sharing. For each disorder, healthy controls seen at the hospital during that same time period were matched for age, weight, and sex to each affected dog to determine risk of disease presentation in the purebred group as compared to that of the mixed-breed population. To enhance reliability of the analyses, sampling of matched healthy to affected dogs was repeated 50 times. For each comparison, the purebred subgroups to mixed-breed odds ratio was determined as was the mean P value used to test this ratio. RESULTS: For aortic stenosis, GDV, early onset cataracts, dilated cardiomyopathy, elbow dysplasia, epilepsy, and portosystemic shunt, most purebred groups were not statistically distinct from the mixed-breed population with higher prevalence in purebreds restricted to distinct subsets of purebred dogs. The conditions of atopy/allergic dermatitis, hypothyroidism, and IVDD were more pervasive across the purebred population with many groups having higher prevalence than the mixed-breed population. The prevalence of IVDD in purebred terrier groups was statistically lower than that observed for mixed-breed dogs. CONCLUSIONS: The results offer an assessment of the distribution of inherited disorders within purebred dogs and illustrate how mixed-breed and subpopulations of purebred dogs do not differ statistically in prevalence for certain disorders. Some disorders appear linked to common ancestors providing insight into disease allele origin whereas others may be due to selection for common structural morphology. Knowledge of the origin of a condition may aid in reducing its prevalence in the dog population as a whole.

Reducing the incidence of epileptic seizures in the Belgian Tervuren through selection.

There is growing evidence that idiopathic epilepsy in the Belgium Tervuren has a genetic foundation. Reducing the incidence of this disorder, which may afflict as much as 17% of the breed, will rely upon the wise selection of parents. Seizure data on 997 dogs from the American Belgian Tervuren Club were collected through questionnaires in which animals were classified into one of four mutually exclusive categories: 1) no seizures observed, 2) one seizure observed, 3) two to five seizures, and 4) more than five seizures. The analysis of this ordered data made use of a threshold model of Bayesian inference. Integration of posterior densities was accomplished through Gibbs sampling. Through this analysis we are able to predict that the offspring of the mating of two non-epileptic dogs has a probability of 0.99 of never suffering from a seizure. The offspring of the mating of two dogs who have each had 1 seizure has a predicted probability 0.58 of never suffering from a seizure. Prevention of this disease is best prescribed through the selection of non-epileptic dogs as parents of future generations.

Gender effects in hearing loss in Dalmatians.

Brainstem auditory-evoked-response data were collected from 3101 Dalmatian dogs from 1984 to 1998 at the Veterinary Medicine Teaching Hospital at the University of California, Davis. Also collected were data on eye color and the presence or absence of a color-patch at birth. Our objective was to evaluate the role of gender in hearing loss, including the possibility that the probability of suffering unilateral or bilateral deafness was greater if the dam was hearing impaired than if the sire was hearing impaired. Results of a multiple-trait threshold-model analysis support the commonly held observation that females were more likely to be deaf than males. In addition, females were also more likely to have two blue eyes (a condition associated with an increased prevalence of deafness). However, gender differences in hearing loss were limited to these direct observations. There was no detectable difference in the prevalence of hearing loss between offspring of deaf mothers and the offspring of deaf fathers. Finally, there was no detectable decrease in the prevalence of hearing loss over the years covered in the data set - suggesting that Dalmatian breeders are not yet selecting against hearing problems.

Boar sperm plasma membrane protein profile: Correlation with the zona-free hamster ova bioassay.

This study was designed to compare differences among porcine sperm plasma membrane proteins with the ability of spermatozoa to interact with zona-free hamster ova. Sperm plasma membrane vesicles were recovered from 24 ejaculates from 10 fertile boars, and from cauda epididymal spermatozoa from 3 fertile and 1 very subfertile boar. Solubilized sperm plasma membrane proteins were run on 1D SDS-PAGE gels, transferred to western blots, stained, and analyzed for quantity of protein per band by scanning laser densitometry. Variation in the quantities of individual sperm plasma membrane proteins in the 20 identified bands were statistically compared with the ability of spermatozoa from the same ejaculate to penetrate zona-free hamster ova. The percentages of plasma membrane protein present in 3 bands (90, 84 and 60 kD) were positively correlated with the ability of spermatozoa from the same ejaculate to fuse with zona-free hamster ova (P = 0.002, 0.01, 0.04; R = 0.53, 0.40, 0.38, respectively). The quantities of protein in 2 other bands (69 and 35 kD) were significantly but negatively correlated with the results of the zona-free hamster ova bioassay (P = 0.02, 0.01; R = -0.42, -0.37, respectively). The sperm plasma membrane profiles were quantitatively similar between the ejaculated samples and the fertile epididymal samples. Six epididymal sperm plasma membrane proteins were present in statistically different quantities in the subfertile boar sample and the 3 fertile controls. The 90 kD band positively correlated with the hamster ova bioassay in the ejaculated samples was not detected in the subfertile epididymal sperm plasma membrane sample. These results suggest that protein(s) in one or more of the 3 positively correlated ejaculated sperm plasma membrane protein bands may be involved in sperm-oocyte interaction.

Inheritance of urinary calculi in the Dalmatian.

Dalmatians are unique among dogs in that they excrete uric acid in their urine as the end product of purine metabolism rather than allantoin as do other breeds of dogs. Urinary calculi form from urate (salts of uric acid) and can cause urethral obstruction in male Dalmatians. Although all Dalmatians have the primary defect, only a subset develops clinical disease. We postulated that calculi formation might have a genetic component that segregates within the breed, causing some animals to form calculi and others to never form calculi despite excreting uric acid in their urine. We used a survey to ascertain the urinary calculi status based on clinical signs of adult Dalmatians aged 6 years or older, and we used pedigrees from these same animals to estimate the heritability of the clinical manifestation of urate calculi within the breed to be .87 (.75-.96). The prevalence of the disease was 34% (24.99-43.70%) among male Dalmatians in our survey. The high heritability of the disease makes it possible for breeders to effectively select against the disease.

The contribution of progeny of uncertain paternity to the accuracy of sire evaluation.

Recent advances in statistical methodology now permit the genetic evaluation of animals with uncertain pedigrees. Although widescale practice of these techniques is not likely, implementation will never occur until we characterize the effect of uncertain pedigrees on the accuracy of animal evaluation. This work develops the framework for such a characterization, illustrating the contribution of uncertainly identified records to accuracy of evaluation through a hypothetical example. The effect of including records of uncertain paternity is greatest for sires with few certainly identified progeny. Thus, young sires stand to benefit the most from the inclusion of progeny records with uncertain paternity. In general, as the level of uncertainty in the data is replaced by the inclusion of progeny with certain paternity, the accuracy of evaluation increases. However, situations do arise in which the accuracy unexpectedly declines with the addition of progeny records with certain paternity.

Identifying single genes of large effect in quantitative traits using best linear unbiased prediction.

The recent discovery of a major gene for rapid postweaning growth has reinforced the hypothesis that other quantitative continuous traits may be influenced by single genes of large effect. However, most methods for the detection of such genes rely on the discovery of multimodality in the population frequency distribution. The complicating effects of environment and artificial selection make the identification of such genes with field-collected data a formidable problem. An index is proposed that may serve as an indicator that a major gene is segregating within a population. The index is based on the assumption that under polygenic inheritance, an offspring's deviation from the midparent average is smaller than the deviation from either parent. Whereas, for the Mendelian segregation of a major gene, the opposite would be expected. A proposed class of indices is then based on the ratio [O - .5(S + D)]k/([O - S]k/2 [O - D]k/2) where O, S and D are the additive genetic values of an offspring and its sire and dam estimated via best linear unbiased prediction. Values of the index greater than 1. would be indicative of major gene inheritance. Simulation of small populations indicates that the index is quite sensitive to the existence of segregating major genes even in the absence of multimodality of the phenotypic distribution. However, the index remains dependent on the accuracy of genetic value estimation.

Simple and rapid inversion of additive relationship matrices incorporating parental uncertainty.

Animals bred in pastoral systems are often part of multiple-sire groups, introducing uncertainty into pedigrees. Genetic evaluation of sires and dams in such instances is complicated by the uncertainty of parenthood. This article defines a simple and rapid algorithm to compute the inverse of a numerator relationship matrix under uncertain parenthood. The algorithm can accommodate inbreeding and uncertainty of parenthood on both paternal and maternal sides of the pedigree.