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O Distl - One of the best experts on this subject based on the ideXlab platform.
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Multiple loci associated with canine hip dysplasia (CHD) in German Shepherd dogs
Mammalian Genome, 2014Co-Authors: Lena Fels, Yvonne Marschall, Ute Philipp, O DistlAbstract:Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we developed 37 informative single nucleotide polymorphisms (SNPs) within 13 quantitative trait loci (QTL) previously identified for German Shepherd dogs. These SNPs were genotyped in 95 German Shepherd dogs affected by CHD and 95 breed, sex, and birth year-matched controls. A total of ten SNPs significant at a nominal P value of 0.05 were validated in 843 German Shepherd dogs including 277 unaffected dogs and 566 CHD-affected dogs. Cases and controls were sampled from the whole German Shepherd dog population in Germany in such a way that mean coancestry coefficients were below 0.1 % within cases and controls as well as among cases and controls. We identified nine SNPs significantly associated with CHD within five QTL on dog chromosomes (CFA) 3, 9, 26, 33, and 34. Genotype effects of these nine SNPs explained between 22 and 34 % of the phenotypic variance of hip dysplasia in German Shepherd dogs. The strongest associated SNPs were located on CFA33 and 34 within the candidate genes PNCP , TRIO , and SLC6A3 . Thus, the present study validated positional candidate genes within five QTL for CHD.
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identification and validation of quantitative trait loci qtl for canine hip dysplasia chd in German Shepherd dogs
PLOS ONE, 2014Co-Authors: Lena Fels, O DistlAbstract:Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we genotyped 96 German Shepherd Dogs affected by mild, moderate and severe CHD and 96 breed, sex, age and birth year matched controls using the Affymetrix canine high density SNP chip. A mixed linear model analysis identified five SNPs associated with CHD scores on dog chromosomes (CFA) 19, 24, 26 and 34. These five SNPs were validated in a by sex, age, birth year and coancestry stratified sample of 843 German Shepherd Dogs including 277 unaffected dogs and 566 CHD-affected dogs. Mean coancestry coefficients among and within cases and controls were <0.1%. Genotype effects of these SNPs explained 20–32% of the phenotypic variance of CHD in German Shepherd Dogs employed for validation. Genome-wide significance in the validation data set could be shown for each one CHD-associated SNP on CFA24, 26 and 34. These SNPs are located within or in close proximity of genes involved in bone formation and related through a joint network. The present study validated positional candidate genes within two previously known quantitative trait loci (QTL) and a novel QTL for CHD in German Shepherd Dogs.
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genetic analyses of elbow and hip dysplasia in the German Shepherd dog
Journal of Animal Breeding and Genetics, 2011Co-Authors: K F Stock, S Klein, Bernd Tellhelm, O DistlAbstract:Summary Results from radiographic screening for canine hip dysplasia (CHD) and elbow dysplasia (CED) of 48 367 German Shepherd dogs born in 2001– 07 were used for the population genetic analyses. Available information included CHD scores for 47 730 dogs, CED scores for 28 011 dogs and detailed veterinary diagnoses of primary ED lesions for a subsample of 18 899 dogs. Quasi-continuous traits were CHD, CED and cases of CED without radiographically visible primary lesion (CED-ARTH). Binary coding was used for fragmented medial coronoid process of the ulna (FCP), borderline findings and mild to severe signs of dysplasia in hip and elbow joints. Genetic parameters were estimated in univariate threshold and multivariate linear and mixed linear-threshold models using Gibbs sampling. Correlations between univariately predicted breeding values (BV) indicated genetic differences between borderline and affected disease status for both CHD (rBV = 0.5) and CED (rBV = 0.3). Multivariate genetic analyses with separate consideration of borderline findings revealed moderate heritabilities of 0.2–0.3 for the quasi-continuous traits with positive additive genetic correlation of 0.3 between CHD and both CED and CED-ARTH. For FCP, heritability of 0.6 and additive genetic correlations of +0.1 to CHD and )0.1 to CEDARTH were estimated. Results supported the relevant genetic determination of CHD and CED, argued for both diseases against interpretation of borderline findings as healthy and implied genetic heterogeneity of CED. Accordingly, future breeding strategies to reduce the prevalences of CHD and CED in the German Shepherd dog should be most efficient when based on BV from multivariate genetic evaluation for CHD, CEDARTH and FCP with use of the whole scale of categories for classification of CHD and CED.
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mapping quantitative trait loci for canine hip dysplasia in German Shepherd dogs
Mammalian Genome, 2007Co-Authors: Yvonne Marschall, O DistlAbstract:Canine hip dysplasia (CHD) is a common hereditary developmental disease of the coxofemoral joints. CHD is characterized by subluxation of the femoral head and deformation of the acetabulum leading to a painful osteoarthrosis. Analyses of mode of inheritance have shown the involvement of a major gene in expression of CHD in German Shepherd dogs. Thus, a whole genome scan for quantitative trait loci (QTL) was performed in German Shepherd dogs. For this purpose 11 paternal half-sib families, including a total of 459 purebred German Shepherd dogs with sires, dams, and offspring, were genotyped for 261 microsatellites. These markers were equidistantly distributed over all 38 autosomes and the X chromosome with an average marker distance of 11.7 cM. The mean observed heterozygosity of the marker set was 50%. The CHD status for the dogs was scored according to the official rules of the Federation Cynologique Internationale. At the genome-wide level of significance at p < 0.05, QTL for CHD were located on nine different canine chromosomes: 1, 3, 4, 8, 9, 16, 19, 26, and 33. The minimal QTL regions containing the CHD genes spanned on average 5 Mb with a range between 1 and 8.2 Mb. Chromosome-wide level of significance at p < 0.05 was found for QTL on 19 chromosomes. Further analyses can now be performed to refine these map positions of QTL already identified in German Shepherd dogs.
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genetic analysis of three different classification protocols for the evaluation of elbow dysplasia in German Shepherd dogs
Journal of Small Animal Practice, 2006Co-Authors: V Janutta, H Hamann, S Klein, Bernd Tellhelm, O DistlAbstract:Objectives: Three different scoring systems for elbow dysplasia and its radiographic signs were genetically evaluated in 2645 German Shepherd dogs. Methods: An animal model was used to estimate heritabilities and additive genetic and residual correlations for the three scoring systems: ED-SV, which is recommended by the International Elbow Working Group; ED-LA, developed by Lang and others; and ED-TH, proposed by Tellhelm. Results: The effects of sex, age at examination and the correlation between the two factors were significant for all three scoring systems. Heritability estimates (se) were 0·18 (0·04) for ED-SV, 0·11 (0·03) for ED-LA and 0.16 (0·04) for ED-TH. The additive genetic correlations among the different single criteria for elbow dysplasia and the different elbow dysplasia scores were between 0·68 and 0·98, except for the criteria ununited anconeal process and osteochondrosis dissecans of the trochlea humeri, which were mostly genetically negatively correlated to the other radiological criteria. Clinical Significance: The elbow dysplasia scores were determined by two genetically different traits. The possibilities for selecting German Shepherd dogs with respect to elbow dysplasia might be improved by taking into account these two traits in the prediction of breeding values.
Bruce G Kornreich - One of the best experts on this subject based on the ideXlab platform.
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cardiomyocyte calcium cycling in a naturally occurring German Shepherd dog model of inherited ventricular arrhythmia and sudden cardiac death
Journal of Veterinary Cardiology, 2013Co-Authors: Sophy A Jesty, Bruce G Kornreich, Shari A Hemsley, Seung Woo Jung, Jonathan M Cordeiro, Teresa M Gunn, Jose M Di Diego, Giles Hooker, Charles Antzelevitch, Sydney N MoiseAbstract:Abstract Objective To further characterize arrhythmic mechanisms in German Shepherd dogs (GSDs) affected with inherited ventricular arrhythmias by evaluating intracellular calcium cycling and expression of calcium handling genes. Animals Twenty five GSDs, 9 backcross dogs, and 6 normal mongrel dogs (controls) were studied. The GSDs and backcross dogs were from a research colony of inherited ventricular arrhythmias. The control research dogs were purchased. Methods Action potentials (APs) and pseudo-electrocardiograms (ECG) were recorded from left ventricular (LV) wedge preparations of GSDs and normal dogs. Midmyocardial (Mid) LV cells from GSDs and normal mongrels were isolated by enzymatic digestion. Cells were either field stimulated or voltage clamped and calcium transients were measured by confocal microscopy using the indicator Fluo-3AM. Expression of calcium handling genes was measured by quantitative RT-PCR. Results Mean calcium transient decay (tau) was not different between affected GSDs and control dogs, but striking cell-to-cell variability for tau was observed within affected GSDs and between affected GSDs and controls (P Conclusions German Shepherd dogs with inherited ventricular arrhythmias have electrophysiologic abnormalities in calcium cycling associated with reduced ATP2A2/SERCA2a expression. These animals provide a unique opportunity to study calcium remodeling at the genetic and molecular level in familial ventricular arrhythmias.
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inherited ventricular arrhythmias and sudden death in German Shepherd dogs
Journal of the American College of Cardiology, 1994Co-Authors: Sydney N Moise, V N Meyerswallen, William J Flahive, B A Valentine, Janet M Scarlett, Cynthia A Brown, Matthew J Chavkin, Dee A Dugger, Shari Renaudfarrell, Bruce G KornreichAbstract:Abstract Objectives. This report describes a unique group of German Shepherd dogs with inherited ventricular arrhythmias and sudden death. Before death, these dogs have no evidence of cardiovascular failure. Background. There are few spontaneous animal models of sudden death that permit intensive investigation. Methods. To determine the temporal evolution of ventricular arrhythmias and to characterize ihe syndrome of sudden cardiac death in these dogs, 24-h ambulatory electrocardiographic (ECG) monitoring, echocardiograms, electrophysiologic testing and breeding studies were conducted. Results. The 24-h ambulatory ECGs from dogs that died showed frequent ventricular arrhythmias with rapid polymorphic ventricular tachycardia (rates > 480 beats/min). Affected dogs had a window of vulnerability for arrhythmias, with the highest incidence and severity of arrhythmias between 20 to 30 and 40 to 50 weeks of age. Affected dogs that died did not have prolongation of the QT interval over a spectrum of heart rates compared with unaffected dogs. The clinical arrhythmia was not induced in dogs during programmed electrical stimulation. Severely affected dogs monitored > 5 years did not develop any evidence of heart failure or cardiomyopathy, and no histopathologic abnormalities existed. Seventeen dogs died suddenly (age 4 to 30 months) and were either 1) found dead at first observation in the morning (n = 8), 2) observed to die during sleep (n = 4), 3) observed to die while resting after exercise (n = 3), or 4) observed to die during exercise (n = 2). All sudden deaths occurred between the end of September and April, with most (n = 11) during January and February. Conclusions. The cause of the inherited severe ventricular arrhythmias and sudden death in these young German Shepherd dogs is still undetermined. A purely arrhythmic disorder is supported by the lack of cardiac pathology. Moreover, the window of vulnerability to ventricular arrhythmias and the age and circumstances of death invite speculation about the role of the autonomic nervous system.
Lena Fels - One of the best experts on this subject based on the ideXlab platform.
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Multiple loci associated with canine hip dysplasia (CHD) in German Shepherd dogs
Mammalian Genome, 2014Co-Authors: Lena Fels, Yvonne Marschall, Ute Philipp, O DistlAbstract:Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we developed 37 informative single nucleotide polymorphisms (SNPs) within 13 quantitative trait loci (QTL) previously identified for German Shepherd dogs. These SNPs were genotyped in 95 German Shepherd dogs affected by CHD and 95 breed, sex, and birth year-matched controls. A total of ten SNPs significant at a nominal P value of 0.05 were validated in 843 German Shepherd dogs including 277 unaffected dogs and 566 CHD-affected dogs. Cases and controls were sampled from the whole German Shepherd dog population in Germany in such a way that mean coancestry coefficients were below 0.1 % within cases and controls as well as among cases and controls. We identified nine SNPs significantly associated with CHD within five QTL on dog chromosomes (CFA) 3, 9, 26, 33, and 34. Genotype effects of these nine SNPs explained between 22 and 34 % of the phenotypic variance of hip dysplasia in German Shepherd dogs. The strongest associated SNPs were located on CFA33 and 34 within the candidate genes PNCP , TRIO , and SLC6A3 . Thus, the present study validated positional candidate genes within five QTL for CHD.
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identification and validation of quantitative trait loci qtl for canine hip dysplasia chd in German Shepherd dogs
PLOS ONE, 2014Co-Authors: Lena Fels, O DistlAbstract:Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we genotyped 96 German Shepherd Dogs affected by mild, moderate and severe CHD and 96 breed, sex, age and birth year matched controls using the Affymetrix canine high density SNP chip. A mixed linear model analysis identified five SNPs associated with CHD scores on dog chromosomes (CFA) 19, 24, 26 and 34. These five SNPs were validated in a by sex, age, birth year and coancestry stratified sample of 843 German Shepherd Dogs including 277 unaffected dogs and 566 CHD-affected dogs. Mean coancestry coefficients among and within cases and controls were <0.1%. Genotype effects of these SNPs explained 20–32% of the phenotypic variance of CHD in German Shepherd Dogs employed for validation. Genome-wide significance in the validation data set could be shown for each one CHD-associated SNP on CFA24, 26 and 34. These SNPs are located within or in close proximity of genes involved in bone formation and related through a joint network. The present study validated positional candidate genes within two previously known quantitative trait loci (QTL) and a novel QTL for CHD in German Shepherd Dogs.
Hans S. Kooistra - One of the best experts on this subject based on the ideXlab platform.
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pituitary dwarfism in 4 German Shepherd dogs
Veterinaria (Cremona), 2010Co-Authors: Stefanie Corradini, A Voorbij, E Mercuriali, S Sella, Hans S. Kooistra, Federico FracassiAbstract:Pituitary dwarfism in German Shepherd dogs is an autosomal, recessive inherited disorder cha-racterized by underdevelopment of the pituitary and a deficiency of growth hormone, thyrotro-pin, prolactin, and the gonadotropins, but unaffected corticotropin secretion. Probably, a muta-tion of a gene encoding a transcription factor that precludes effective expansion of pituitary stem cells after differentiation of the corticotropic cells is the cause of this disorder. Identifica-tion of the mutation would enable the development of a DNA test for potential breeding animals and could lead to the eradication of this condition. The main clinical manifestations of pituitary dwarfism are proportionate growth retardation and alopecia. Definite diagnosis should ideally rely on the results of a combined pituitary anterior lobe function test. Although the prognosis improves significantly when dwarfs are properly treated with levo-thyroxine and either porcine growth hormone or progestins, the prognosis remains guarded.
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the leukemia inhibitory factor receptor gene is not involved in the etiology of pituitary dwarfism in German Shepherd dogs
Research in Veterinary Science, 2006Co-Authors: J M Hanson, Peter A.j. Leegwater, Hans S. Kooistra, Björn P. MeijAbstract:Abstract Pituitary dwarfism in German Shepherd dogs is characterized by combined pituitary hormone deficiency (CPHD) and intrapituitary cyst formation. Activation of the leukemia inhibitory factor (LIF)–LIF receptor (LIFR) signal transduction pathway results in a similar phenotype in (transgenic) mice. We therefore assessed the role of the LIFR in the etiology of pituitary dwarfism in German Shepherd dogs. A polymorphic microsatellite marker (UULIFR) was used to analyze the segregation of the LIFR gene in 22 German Shepherd dogs from 4 pedigrees, each including one dwarf. There was no allelic association between UULIFR and the dwarfism phenotype. Based on our findings LIFR was excluded as a candidate gene for CPHD.
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exclusion of the lim homeodomain gene lhx4 as a candidate gene for pituitary dwarfism in German Shepherd dogs
Molecular and Cellular Endocrinology, 2002Co-Authors: Bernard A Van Oost, Sandra Imholz, Serge A Versteeg, Hans S. KooistraAbstract:Pituitary dwarfism in the German Shepherd dog is an autosomal recessive inherited abnormality. We tested the hypothesis that a variant of the LIM homeodomain gene LHX4 is responsible for the dwarfism phenotype. To this end, we isolated Bacterial Artificial Chromosome clones for the canine LHX4 gene. Southern blotting experiments showed that the LHX4 gene is a single copy gene in the canine genome. A complex CA-repeat was isolated from the BAC clones and was found to be polymorphic in German Shepherd dogs. Genotyping 5 litters in which the dwarfism was segregating showed disconcordance between the inheritance of the dwarfism phenotype and the DNA marker. It is concluded that the LHX4 gene does not play a primary role in the pituitary dwarfism in the German Shepherd dogs.
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combined pituitary hormone deficiency in German Shepherd dogs with dwarfism
Domestic Animal Endocrinology, 2000Co-Authors: Hans S. Kooistra, G Voorhout, A RijnberkAbstract:Abstract In German Shepherd dogs pituitary dwarfism is known as an autosomal recessive inherited abnormality. To investigate whether the function of cells other than the somatotropes may also be impaired in this disease, the secretory capacity of the pituitary anterior lobe (AL) cells was studied by a combined pituitary AL stimulation test with four releasing hormones (4RH test) in four male and four female German Shepherd dwarfs. In addition, the morphology of the pituitary was investigated by computed tomography. The physical features of the eight German Shepherd dwarfs were primarily characterized by growth retardation and stagnant development of the hair coat. The results of the 4RH test confirmed the presence of hyposomatotropism. The basal plasma TSH and prolactin concentrations were also low and did not change upon stimulation. Basal plasma concentrations of LH were relatively low and responded only slightly to suprapituitary stimulation. With respect to the plasma FSH levels there was a clear gender difference. In the males plasma FSH concentrations remained below the detection limit throughout the 4RH test, whereas in the females the basal plasma FSH levels were slightly lower and there was only a small increase following suprapituitary stimulation, compared with the values in age-matched controls. In contrast, basal and stimulated plasma ACTH concentrations did not differ between the dwarfs and the controls. Computed tomography of the pituitary fossa revealed a normal sized pituitary with cysts in five dogs, an enlarged pituitary with cysts in two dogs, and a small pituitary gland without cysts in the remaining dog. The results of this study demonstrate that German Shepherd dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, whereas ACTH secretion is preserved. The combined pituitary hormone deficiency is associated with cyst formation and pituitary hypoplasia.
Yvonne Marschall - One of the best experts on this subject based on the ideXlab platform.
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Multiple loci associated with canine hip dysplasia (CHD) in German Shepherd dogs
Mammalian Genome, 2014Co-Authors: Lena Fels, Yvonne Marschall, Ute Philipp, O DistlAbstract:Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we developed 37 informative single nucleotide polymorphisms (SNPs) within 13 quantitative trait loci (QTL) previously identified for German Shepherd dogs. These SNPs were genotyped in 95 German Shepherd dogs affected by CHD and 95 breed, sex, and birth year-matched controls. A total of ten SNPs significant at a nominal P value of 0.05 were validated in 843 German Shepherd dogs including 277 unaffected dogs and 566 CHD-affected dogs. Cases and controls were sampled from the whole German Shepherd dog population in Germany in such a way that mean coancestry coefficients were below 0.1 % within cases and controls as well as among cases and controls. We identified nine SNPs significantly associated with CHD within five QTL on dog chromosomes (CFA) 3, 9, 26, 33, and 34. Genotype effects of these nine SNPs explained between 22 and 34 % of the phenotypic variance of hip dysplasia in German Shepherd dogs. The strongest associated SNPs were located on CFA33 and 34 within the candidate genes PNCP , TRIO , and SLC6A3 . Thus, the present study validated positional candidate genes within five QTL for CHD.
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mapping quantitative trait loci for canine hip dysplasia in German Shepherd dogs
Mammalian Genome, 2007Co-Authors: Yvonne Marschall, O DistlAbstract:Canine hip dysplasia (CHD) is a common hereditary developmental disease of the coxofemoral joints. CHD is characterized by subluxation of the femoral head and deformation of the acetabulum leading to a painful osteoarthrosis. Analyses of mode of inheritance have shown the involvement of a major gene in expression of CHD in German Shepherd dogs. Thus, a whole genome scan for quantitative trait loci (QTL) was performed in German Shepherd dogs. For this purpose 11 paternal half-sib families, including a total of 459 purebred German Shepherd dogs with sires, dams, and offspring, were genotyped for 261 microsatellites. These markers were equidistantly distributed over all 38 autosomes and the X chromosome with an average marker distance of 11.7 cM. The mean observed heterozygosity of the marker set was 50%. The CHD status for the dogs was scored according to the official rules of the Federation Cynologique Internationale. At the genome-wide level of significance at p < 0.05, QTL for CHD were located on nine different canine chromosomes: 1, 3, 4, 8, 9, 16, 19, 26, and 33. The minimal QTL regions containing the CHD genes spanned on average 5 Mb with a range between 1 and 8.2 Mb. Chromosome-wide level of significance at p < 0.05 was found for QTL on 19 chromosomes. Further analyses can now be performed to refine these map positions of QTL already identified in German Shepherd dogs.