Pedigree analysis of the Hungarian Thoroughbred population

The aim of the study was to analyse the pedigree information of Thoroughbred horses which were participating in gallop races between 1998 and 2010 in Hungary. Among the 3043 individuals of the reference population there were imported animals from foreign countries (e.g. Germany, England or Ireland) and horses that were born in Hungary. The number of complete generations was 15.64 (varied between 0 for the founders and 25.20), the mean number of full generations was 6.69, and the mean maximum generations were 28.96. The number of founders was 1062, and the effective number of founders was 42. Two hundred and thirty-two founders were born before 1793 (when the stud book of the Thoroughbred breed was closed), therefore these founders are considered as true founders of the breed. These 232 founders were responsible for 88.58% of the gene pool in the reference genome. The significant difference between the number of founders and effective number of founders indicate that the genetic diversity decreased greatly from the founders to the reference population. The number of ancestors was 908 and only 6 of them were responsible for 50% of the genetic diversity in the examined population. The effective number of ancestors was 15.32. From the ratio of the effective number of founders and effective number of ancestors we concluded to a bottleneck effect that characterizes the pedigree under study. Generation interval was more than a year longer for stallions (12.17) than it was for mares (10.64). More than 94% of the individuals in the pedigree were inbred, and the average inbreeding of the population was 9.58%. Considering the changes of the inbreeding status of the examined population 4 large time periods were appointed. The first lasted until 1780, the second period was from 1780 until 1952, the third period was between 1946 and 1998 and the last one was from 1998 until 2008. Rate of inbreeding in the last generation was 0.3%, which forecasts further increase in inbreeding. The effective population size was above 100 in the last 30 generations, proving the genetic diversity did not decrease by a level that would make long-term selection impossible.     

Prediction of the genetic risk for fragmented coronoid process in labrador retrievers

In a cohort of 252 Dutch labrador retrievers born between 1988 and 1992, seven founders for fragmented coronoid process were identified. The 185 labrador retrievers born to this cohort between January 1, 1993 and January 1, 1997, were examined clinically, and radiographs of both elbows taken in four directions at 12 to 18 months of age, or earlier when they had signs of lameness, were evaluated. The diagnosis of fragmented coronoid process was confirmed by arthrotomy. The incidence of the condition in the 185 dogs was 17.3 per cent, and for each dog a genetic risk factor was calculated on the basis of its relatedness to the seven founders. The risk factors ranged from 0.07 to 0.41. The dogs were divided into classes of increasing predicted risk, and the mean risk for each class was then compared with the clinical outcome. There were no significant differences between the predicted risk and the outcome in any of the classes.     

Copper Toxicosis in Bedlington Terriers

Copper toxicosis of Bedlington Terriers (Chronic progressive hepatitis) is a genetically transmitted disease. The typical feature of this disease is accumulation of copper in the liver tissue. The changes vary from mild hepatitis to chronic progressive hepatitis and cirrhosis.The material of this study consists of 2 cases of copper toxicosis examined at the Department of Pathology in Helsinki in the years 1980–82. Moreover a re-examination of tissue samples was made of all Bedlington Terriers examined during the years 1969–1982 at the same department. Six of the 14 examined dogs showed a positive reaction for copper in their liver tissues. The possible relationship of the examined dogs is not yet known.     

Evaluation of haplotypes associated with copper toxicosis in Bedlington Terriers in Australia

OBJECTIVE: To evaluate the haplotype distribution associated with the copper toxicosis gene and the segregation of the mutated allele in a Bedlington Terrier population in Australia. ANIMALS: 131 Bedlington Terriers. PROCEDURE: Samples of DNA and RNA were obtained from each dog. Genetic status of each dog was evaluated by use of the DNA markers C04107; single nucleotide polymorphism (SNP), which was adjacent to exon 2 of Murr1; and a deletion marker for exon 2. A subgroup of the study population was evaluated by use of biochemical and histologic techniques to elucidate the correlation between genotype and phenotype. RESULTS: We identified a recombination between the C04107 marker and Murr1 and a variation in a nucleotide in the splice site of exon 2 in our Bedlington Terrier cohort. Furthermore, we identified a novel haplotype associated with copper toxicosis in this cohort. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings indicate that the deletion of exon 2 was not the sole cause of copper toxicosis, although only exon 2 deletion of Murr1 has been responsible for copper toxicosis in Bedlington Terriers. Although we failed to find a novel mutation in our cohort, we identified an affected dog family with an intact exon 2. Furthermore, we found that an SNP in the 5' splicing site of exon 2 may or may not be associated with a novel mutation of the Murr1 gene or other genes. Loss of linkage between the C04107 marker and the Murr1 gene was also identified in a certain family of dogs.     

Genetic diversity in Polish hounds estimated by pedigree analysis

Data from 247 litters of Polish hounds born at 105 kennels between 1960 and 2004 was analysed in order to evaluate the genetic variability of the breed. The breed originated from 19 founders and the founder genome equivalent ranged from 2.043 to 1.287 over the span of forty-four years of breeding. The high imbalance of founder contributions to the gene pool was noted, with the dominant contribution of four founders. The low number of the founders and the high disproportion of particular dogs in breeding use resulted in the increasing value of inbreeding coefficient which ranged from 0.0771 to 0.370. The poor gene pool seems to be strictly connected to the deteriorating health of the population which draws into question the future of the breed.     

Population structure and genetic diversity of worldwide Nova Scotia Duck Tolling Retriever and Lancashire Heeler dog populations

The aim of this study was to research the population structure and genetic diversity of the Nova Scotia Duck Tolling Retriever (NS) and the Lancashire Heeler (LH) dog breeds. Data consisted of nearly all the worldwide registration history for both breeds, including 28 668 NS and 4 782 LH individuals. A reference population, including the females born between 1999 and 2008, was defined for genetic analyses for each breed. Average depth of the pedigrees known for the reference population dogs was 12.9 complete generation equivalents in the NS and 6.0 in the LH. Only a small fraction of the born dogs were used later for breeding. Effective number of founders was 9.8 in the NS and 15.2 in the LH. More than 50% of the genetic diversity in the reference population was explained by two ancestors in the NS and five in the LH. Average inbreeding coefficients in the reference populations were 0.26 in the NS and 0.10 in the LH. Average kinships were 0.26 and 0.08 and realised effective population sizes 18 and 28, respectively. Failure to use available genetic resources for sustainable breeding has resulted in depletion of genetic variation in both breeds. To increase genetic variation, a larger proportion of the dogs should be used in reproduction and the contributions of reproducing animals should be equalized. In the LH, it is necessary to use the unregistered farm dogs in breeding. In the NS, crosses with another breed are needed.     

Use of zinc acetate to treat copper toxicosis in dogs.

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.     

Copper-associated liver disease in Dalmatians: a review of 10 dogs (1998-2001)

This retrospective study summarizes 10 Dalmatians suspected of having hepatic copper toxicosis. Hepatic copper toxicosis can result from either a primary metabolic defect in hepatic copper metabolism or from altered hepatic biliary excretion of copper. An inherited copper-associated hepatopathy has been documented in Bedlington Terriers, and there is evidence for familial copper-associated liver disease in West Highland White (WHW) Terriers and Skye Terriers. Nine of the 10 Dalmatians in this study presented for gastrointestinal clinical signs, including anorexia and vomiting. All animals had increased alanine aminotransferase (ALT) enzyme activity, and 9 of 10 had increased alkaline phosphatase (ALP) enzyme activity. The relative increase in ALT activity was much greater than the relative increase in ALP activity, suggesting a predominantly hepatocellular rather than cholestatic liver disease. The mean hepatic copper concentration for 9 Dalmatians was 3,197 microg/g dry weight liver (dwl) (normal, <450 microg/g). In 5 of these 9 dogs, hepatic copper concentrations exceeded 2,000 microg/g dwl. Necroinflammatory alterations associated with copper-laden parenchymal cells were the notable histopathologic finding. The inflammatory infiltrate was either primarily lymphocytic or neutrophilic. Morphologic features of cholestasis generally were not prominent except in those dogs with severe pathology. These findings lend support to the hypothesis that a primary metabolic defect in hepatic copper metabolism occurs in the Dalmatian breed. The mechanism and genetic basis of this condition require further study.     

Rates of inbreeding and genetic diversity in Iranian Holstein Cattle

The accumulation of inbreeding and the loss of genetic diversity is a potential problem in Holstein dairy cattle. The goal of this study was to estimate inbreeding levels and other measures of genetic diversity, using pedigree information from Iranian Holstein cattle. Edited pedigree included 1 048 572 animals. The average number of discrete generation equivalents and pedigree completeness index reached 13.4 and 90%, respectively. The rate of inbreeding was 0.3% per year. Effective number of founders, founder genomes, non‐founders and ancestors of animals born between 2003 and 2011 were 503, 15.6, 16.1 and 25.7, respectively. It was proven that the unequal founder contributions as well as bottlenecks and genetic drift were important reasons for the loss of genetic diversity in the population. The top 10 ancestors with the highest marginal genetic contributions to animals born between 2003 and 2011 and with the highest contributions to inbreeding were 48.20% and 63.94%, respectively. Analyses revealed that the most important cause of genetic diversity loss was genetic drift accumulated over non‐founder generations, which occurred due to small effective population size. Therefore, it seems that managing selection and mating decisions are controlling future co‐ancestry and inbreeding, which would lead to better handling of the effective population size.     

Use of 64Copper Measurements to Diagnose Canine Copper Toxicosis

Inherited canine copper toxicosis is a serious problem in Bedlington terriers and West Highland White terriers, and may also be a problem in other less-studied breeds. Affected dogs become ill at midlife with progressive and ultimately fatal liver disease. Treatments for removal of copper and prevention of copper accumulation are available, but are most effective if begun before the dog becomes ill. Until recently diagnosis has not been available until the dog is 1 year of age, and then only by an invasive liver biopsy with determination of liver copper concentration. The authors studied the use of 64copper for early diagnosis of canine copper toxicosis. Two procedures were evaluated. The first involved measuring the concentration of 64copper in blood 24 hours after oral administration of the radioisotope. At this time, 64copper was associated primarily with ceruloplasmin secreted into the blood by the liver. This procedure is useful in the diagnosis of the human counterpart, Wilson's disease. However, the authors found it to be nondiscriminatory between affected and unaffected dogs. In contrast, the second procedure, which involved measuring 64copper excreted in stool during 48 hours after an intravenous dose of radioisotope, yielded results that differentiated most affected and unaffected dogs.     

Microsatellite marker C04107 as a diagnostic marker for copper toxicosis in the Danish population of Bedlington terriers

The linkage phase of marker C04107 was evaluated before implementation of the marker in a diagnostic test. Blood samples from 68 dogs were collected and genotyped by PCR. Two alleles were detected with sizes of 160 bp and 164 bp and allele frequencies of 0.45 and 0.55 respectively. Genotyping revealed that 35 dogs were heterozygous (51.5%), 22 dogs were homozygous for the normal allele (32.3%) and 11 dogs were homozygous for the disease allele (16.2%). Liver biopsies were taken from 14 selected dogs and the copper content was evaluated histologically. Biopsies from 8 dogs homozygous for the disease allele showed many copper granules along with single cell necrosis, haemosiderosis and cellular infiltration. In liver biopsies from 6 dogs genotyped to be heterozygous or homozygous for the normal allele, copper granules were absent or moderate in number and no lesions were present. The survey demonstrates that the linkage phase of marker C04107 in the Danish population of Bedlington terriers is similar to the linkage phase detected in other countries. Thus, the marker can be used in a diagnostic test for copper toxicosis in Denmark.     

Familial clustering and risk analysis for fragmented coronoid process and elbow joint incongruity in Bernese Mountain Dogs in The Netherlands.

OBJECTIVE: To analyze familial clustering and genetic risk for various forms of elbow dysplasia (ED) in Bernese Mountain Dogs (BMD) in The Netherlands and define possible means to select against ED. ANIMALS: 98 BMD born in 1992 and 64 BMD born in 1995. PROCEDURE: Dogs were examined radiographically when 12 to 18 months old. The population was resolved into familial clusters, and distribution of ED for the clusters was analyzed. Common ancestors associated with each form of ED were identified, and risk for having ED in the 64 offspring born in 1995 was calculated by relatedness to common ancestors. Risk was compared with radiographic outcome. RESULTS: The 2 forms of ED identified were fragmented coronoid process (FCP) and elbow joint incongruity (INC). Incidence of ED decreased from 63/98 (64%) in 1992 to 29/64 (45%) in 1995. None of the familial clusters was free of FCP or INC. Common ancestors associated with FCP differed from those associated with INC. There was more potential variation in risk for FCP and INC in the 64 offspring than was achieved by breeders, indicating a decrease in population heterogeneity. CONCLUSIONS AND CLINICAL RELEVANCE: FCP and INC had differing familial sources; thus, they most likely are different genetic traits. Although incidence of ED decreased from 1992 through 1995, we did not detect variation among pedigrees in genetic risk for ED remaining in the offspring born in 1995; thus, selection among families cannot further improve ED health status of BMD in The Netherlands. Phenotypic selection within families remains the only alternative.     

Population structure and genetic variability in the Murrah dairy breed of water buffalo in Brazil accessed via pedigree analysis

The objective of this study was to use pedigree analysis to evaluate the population structure and genetic variability in the Murrah dairy breed of water buffalo (Bubalus bubalis) in Brazil. Pedigree analysis was performed on 5,061 animals born between 1972 and 2002. The effective number of founders (fe) was 60, representing 6.32?% of the potential number of founders. The effective number of ancestors (fa) was 36 and the genetic contribution of the 17 most influent ancestors explained 50?% of the genetic variability in the population. The ratio fe/fa (effective number of founders/effective number of ancestors), which expresses the effect of population bottlenecks, was 1.66. Completeness level for the whole pedigree was 76.8, 49.2, 27.7, and 12.8?% for, respectively, the first, second, third, and fourth known parental generations. The average inbreeding values for the whole analyzed pedigree and for inbreed animals were, respectively, 1.28 and 7.64?%. The average relatedness coefficient between individuals of the population was estimated to be 2.05?%??the highest individual coefficient was 10.31?%. The actual inbreeding and average relatedness coefficient are probably higher than estimated due to low levels of pedigree completeness. Moreover, the inbreeding coefficient increased with the addition of each generation to the pedigree, indicating that incomplete pedigrees tend to underestimate the level of inbreeding. Introduction of new sires with the lowest possible average relatedness coefficient and the use of appropriate mating strategies are recommended to keep inbreeding at acceptable levels and increase the genetic variability in this economically important species, which has relatively low numbers compared to other commercial cattle breeds. The inclusion of additional parameters, such as effective number of founders, effective number of ancestors, and fe/fa ratio, provides better resolution as compared to the inclusion of inbreeding coefficient and may help breeders and farmers adopt better precautionary measures against inbreeding depression and other deleterious genetic effects.     

Copper inhibition of the thiobarbituric acid reaction in Bedlington terriers

The effect of copper on thiobarbituric acid (TBA) reaction values, an index of lipid peroxidation, was examined in Bedlington Terriers, healthy dogs, and rats. High hepatic concentrations of copper appeared to lower TBA values in the inherited, chronic, progressive hepatic degeneration of Bedlington Terriers, a disease associated with copper toxicosis. The suspected TBA inhibition was confirmed when Cu2+ was added to homogenates of healthy dog or rat liver or a malondialdehyde standard. The amount of copper added approximated that in diseased Bedlington Terriers. Because of the interference by copper, the TBA test was judged to be an inappropriate test for the evaluation of lipid peroxidation in samples containing high copper concentrations such as those in diseased Bedlington Terriers.     

Genetic variability in Hanoverian warmblood horses using pedigree analysis

A data set constituting a total of 310,109 Hanoverian warmblood horses was analyzed to ascertain the genetic variability, coefficients of inbreeding, and gene contributions of foreign populations. The reference population contained all Hanoverian horses born from 1980 to 2000. In addition, Hanoverian stallions born from 1980 to 1995 and Hanoverian breeding mares from the birth years 1980 to 1995 with registered foals were analyzed for the same genetic parameters. The average complete generation equivalent was approximately 8.43 for the reference population. The mean coefficient of inbreeding was 1.33, 1.19, and 1.29% for the reference population, stallions, and breeding mares, respectively. The effective number of founders was largest in stallions (364.3) and smallest in the reference population (244.9). The ratio between the effective number of founders and the effective number of ancestors was 3.15 for the reference population, 3.25 for the stallions, and 3.06 for the breeding mares. The effective population size in the Hanoverian warmblood reference population was 372.34. English Thoroughbreds contributed nearly 35% of the genes to the Hanoverian reference population and even slightly greater contributions (39%) to the stallions. Trakehner and Arab horses contributed approximately 8 and 2.7%, respectively, to the Hanoverian gene pool. The most important male ancestors were Aldermann I from the A/E line, Fling from the F/W line, and Absatz from the Trakehner line, whereas the breeding mare Costane had the greatest contribution to the reference population, stallions, and breeding mares. From 1996 onward, the stallions Weltmeyer and Donnerhall had the largest genetic impact on the Hanoverian horse population.     

Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier King Charles Spaniels

Occipital bone hypoplasia with foramen magnum obstruction and secondary syringomyelia (SM) is a common condition in the Cavalier King Charles Spaniel (CKCS) that is similar to human Chiari type I malformation. A worldwide family tree of more than 5,500 CKCSs spanning a maximum of 24 generations was established by obtaining pedigree information from 120 dogs diagnosed with SM secondary to occipital bone hypoplasia. The ongoing study showed 6 of 8 great grandparents of all affected dogs could be traced back to 2 female ancestors so that all 8 were descended from one or the other or both. The disease appears to be more severe and have an earlier onset with increased inbreeding, especially when breeding from affected dogs. The family tree of idiopathic epilepsy (IE) appears to be a different subset of the CKCS population, although some overlap was observed. Idiopathic epilepsy is more frequent in lines originating from whole-color dogs. Selection for coat color is believed to have influenced the development of both occipital hypoplasia with secondary SM and IE. In addition, breeding guidelines to reduce the incidence of mitral valve disease have placed further pressures on the gene pool.     

Inherited copper toxicosis in the Bedlington terrier: the prevalence in asymptomatic dogs

Copper toxicosis in the Bedlington terrier is an inherited defect. This paper describes the investigation of 62 Bedlington terriers, none of which had shown any clinical signs of liver disease, in order to assess the prevalence of copper toxicosis in the breed in the United Kingdom. Twenty one (33·9 per cent) of the dogs investigated had abnormally high levels of copper in the liver. No reliable circulating haematological or biochemical parameters were found to identify those dogs with increased hepatic copper levels and the diagnosis could only be established by liver biopsy. Affected dogs had liver copper levels of between 257·5 and 2558·0 μpg per g of wet weight (1163·8 ± 164 μg/g, mean ± SEM) compared with normal dogs which had between 9·9 and 118·6 μg/g of wet weight (49·0 & 4·4 μg/g, mean ± SEM). Copper accumulation in the liver of affected dogs could also be detected on histological examination using special stains.     

Status Epilepticus and Epileptic Seizures in Dogs

Background: A special form of epileptic seizures (ES) is the life-threatening condition of status epilepticus (SE), which requires immediate and specific treatment based on a correct diagnosis of the underlying disease condition.
Hypothesis/Objectives: The objectives of this retrospective study were to determine prevalence of ES and SE in dogs presenting at a veterinary teaching hospital, to identify the etiology and relative risk (RR) for SE in general and at the onset of seizures. Furthermore the outcome for dogs suffering from SE was to be evaluated.
Animals: Three hundred and ninety-four dogs that were admitted to a veterinary teaching hospital (January 1, 2002 to March 31, 2008) with ES.
Methods: All medical records of dogs with ES were identified by screening the clinical documentation system and evaluated for inclusion in this retrospective study.
Results: Dogs with reactive seizures caused by poisoning had a significantly higher risk of developing SE ( P < .001; RR = 2.74), particularly as 1st manifestation of a seizure disorder ( P = .001; RR = 1.97). After SE, dogs with symptomatic epilepsy had a significantly lower probability of survival than dogs with idiopathic epilepsy ( P < .001) and reactive ESs ( P = .005).
Conclusion and Clinical Importance: In dogs showing SE as the 1st manifestation of a seizure disorder, intoxication should always be considered and appropriate investigations undertaken. Dogs with SE owing to toxicosis have more favorable outcomes than dogs with symptomatic epilepsy ( P < .001).     

Mushroom toxicosis in dogs in general practice causing gastroenteritis,ptyalism and elevated serum lipase activity

Mushroom toxicosis is rarely diagnosed in dogs and is poorly reported in the veterinary literature. This report suggests that mushroom toxicosis is a potentially under‐diagnosed condition in first opinion practice in the UK. Nine dogs with clinical signs consistent with mushroom toxicosis were identified from the records of an out‐of‐hours emergency service between August 2010 and January 2011. Four dogs were later excluded because of clinical inconsistencies. Clinical signs included acute profuse ptyalism (5/5), diarrhoea (5/5), vomiting (4/5), hypovolaemia (4/5), stuporous (3/5) or obtunded mentation (1/5), miosis (2/5) and hypothermia (2/5). Serum lipase activity was elevated in 4/4 dogs; canine‐specific pancreatic lipase was elevated in the remaining dog. Four dogs recovered with aggressive intravenous fluid therapy, analgesia and supportive care; the remaining dog was euthanased due to severe clinical signs and financial constraints. Mushroom toxicosis is an important differential diagnosis for acute gastroenteritis and one possible cause of some cases of “Seasonal Canine Illness”. Affected dogs may demonstrate elevated pancreatic enzymes and mushroom toxicosis should be considered in cases of elevated lipase or abnormal semi‐quantitative canine‐specific pancreatic lipase activities.     

Retrospective study of toxic metal analyses requested at a veterinary diagnostic toxicology laboratory in Ontario (1990-1995).

During the 5-year period from January 1, 1990, to December 31, 1995, 887 diagnoses of metal toxicosis in domestic animals and wild birds were documented at the Veterinary Laboratory Services Branch of the Ontario Ministry of Agriculture, Food and Rural Affairs. Most of these cases involved cattle, sheep, and birds. Lead toxicosis was diagnosed in 399 cases, copper toxicosis in 387, zinc toxicosis in 49, mercury toxicosis in 44, iron toxicosis in 4, and selenium in 4 cases. Trends in species affected and sources of metals are discussed.