%0 Journal Article %K bleeding disorder %K factor VIII activity %K mutation %K PCR %K protein modeling %B Berliner und Münchener Tierärztliche Wochenschrift %C Hannover %D 2017 %G English %I Schlütersche Verlagsgesellschaft mbH & Co. KG %R 10.2376/0005-9366-15121 %T Canine haemophilia A caused by a thymine to cytosine nucleotide exchange at nucleotide position 6217 in a Great Dane %V 130 %1 {"oldId":101188,"title":"Canine haemophilia A caused by a thymine to cytosine nucleotide exchange at nucleotide position 6217 in a Great Dane","topline":"","teaserText":"Canine H\u00e4mophilie A bei einer Deutschen Dogge, verursacht durch einen Thymin zu Cytosin Nukleotidaustausch an der Nukleotidposition 6217","content":"

Summary<\/span>
A male Great Dane was referred to the Small Animal Clinic, University of Veterinary Medicine Hannover at seven months of age with a known bleeding history. The dog was diagnosed with haemophilia A (factor VIII activity: 4%). To identify the underlying genetic defect responsible for haemophilia in the patient, the coding region and exon-intron boundaries of the canine factor VIII gene were analysed by polymerase chain reaction and electrophoresis. 25 Great Danes and 25 individuals of three different breeds each served as controls. Sequence analysis of exon 21 of the canine FVIII gene of the patient showed a thymine to cytosine nucleotide exchange at nucleotide position 6217, which results in a tryptophan to arginine exchange. None of the remaining dogs studied showed the mutation. Analysis using several protein models demonstrated that the altered amino acid is located in the C1 domain of the canine FVIII protein and results in a change of the protein structure. To the knowledge of the authors, this is the first known mutation of the factor VIII gene in a Great Dane associated with haemophilia A.<\/p>

Keywords<\/span>
bleeding disorder, factor VIII activity, mutation, PCR, protein modeling<\/p>

Zusammenfassung<\/span>
Eine siebenj\u00e4hrige Deutsche Dogge wurde in die Klinik f\u00fcr Kleintiere der Tier\u00e4rztlichen Hochschule Hannover aufgrund von Blutungen \u00fcberwiesen. Dort wurde eine H\u00e4mophilie A (Faktor VIII-Aktivit\u00e4t: 4%) diagnostiziert. Um den verantwortlichen Gendefekt f\u00fcr die H\u00e4mophilie bei diesem Patienten identifizieren zu k\u00f6nnen, wurden die kodierenden Regionen und Exon-Intron-Grenzen des caninen Faktor VIII Gens mit Hilfe von Polymerase Kettenreaktion und Elektrophorese analysiert. Kontrollmessungen erfolgten an 25 Deutschen Doggen und jeweils 25 Individuen von drei anderen Rassen. Die Sequenzanalyse von Exon 21 des caninen Faktor VIII Gens identifizierte einen Thymin zu Cytosin Basenaustausch an der Nukleotidposition 6217, welcher einen Austausch von Tryptophan durch Arginin zur Folge hat. Keiner der anderen untersuchten Hunde zeigte die Mutation. Die Analysen mit verschiedenen Proteinmodellen zeigten, dass die ge\u00e4nderte Aminos\u00e4ure in der C1-Dom\u00e4ne des caninen Faktor VIII Proteins lokalisiert ist und eine ver\u00e4nderte Struktur dieses Proteins zur Folge hat. Nach Kenntnis der Autoren ist dies die erste bekannte, f\u00fcr eine H\u00e4mophilie A verantwortliche Mutation des Faktor VIII Gens in einer Deutschen Dogge.<\/p>

Schl\u00fcsselw\u00f6rter<\/span>
Gerinnungsst\u00f6rung, Faktor VIII-Aktivit\u00e4t, Mutation, PCR, Proteinmodelle<\/p>","categories":["Tier\u00e4rztliche Wochenschrift","Abostufe BMTW","Fachartikel"],"fromDate":"Mar 7, 2017 11:00:00 PM","oldUrls":["http:\/\/vetline.de\/canine-haemophilia-a-caused-by-a-thymine-to-cytosine-nucleotide-exchange-at-nucleotide-position-6217-in-a-great-dane\/150\/3130\/101188"],"doiLanguage":"englisch","doiProductFormat":"online","doiPublisher":"Schl\u00fctersche Verlagsgesellschaft mbH & Co. KG","doiSerialWorkTitle":"Berliner und M\u00fcnchener Tier\u00e4rztliche Wochenschrift","doiDocumentUri":"http:\/\/www.vetline.de\/canine-haemophilia-a-caused-by-a-thymine-to-cytosine-nucleotide-exchange-at-nucleotide-position-6217-in-a-great-dane\/150\/3130\/101188\/","doiSource":"Berliner und M\u00fcnchener Tier\u00e4rztliche Wochenschrift 2017","doiissn":"0005-9366","doiNr":"10.2376\/0005-9366-15121","doiFirstPage":".","doiLastPage":"..","doiTransmitted":true,"doiAuthor":"Alcaraz Rodr\u00edguez P, Kehl A, Cecil A, Shityakov S, Dandekar T, Mueller E, Mischke R","pdf":{"path":"http:\/\/data\/BMW_AOP_15121.pdf","title":"BMW_AOP_15121.pdf","description":"Canine haemophilia A caused by a thymine to cytosine nucleotide exchange at nucleotide position 6217 in a Great Dane "},"authors":[{"firstName":"P","middleName":"","lastName":"Alcaraz Rodr\u00edguez"},{"firstName":"A","middleName":"","lastName":"Kehl"},{"firstName":"A","middleName":"","lastName":"Cecil"},{"firstName":"S","middleName":"","lastName":"Shityakov"},{"firstName":"T","middleName":"","lastName":"Dandekar"},{"firstName":"E","middleName":"","lastName":"Mueller"},{"firstName":"R","middleName":"","lastName":"Mischke"}],"contentOptimised":"

Summary<\/strong>
A male Great Dane was referred to the Small Animal Clinic, University of Veterinary Medicine Hannover at seven months of age with a known bleeding history. The dog was diagnosed with haemophilia A (factor VIII activity: 4%). To identify the underlying genetic defect responsible for haemophilia in the patient, the coding region and exon-intron boundaries of the canine factor VIII gene were analysed by polymerase chain reaction and electrophoresis. 25 Great Danes and 25 individuals of three different breeds each served as controls. Sequence analysis of exon 21 of the canine FVIII gene of the patient showed a thymine to cytosine nucleotide exchange at nucleotide position 6217, which results in a tryptophan to arginine exchange. None of the remaining dogs studied showed the mutation. Analysis using several protein models demonstrated that the altered amino acid is located in the C1 domain of the canine FVIII protein and results in a change of the protein structure. To the knowledge of the authors, this is the first known mutation of the factor VIII gene in a Great Dane associated with haemophilia A.<\/p>

Keywords:<\/strong>
bleeding disorder, factor VIII activity, mutation, PCR, protein modeling<\/p>

Zusammenfassung<\/strong>
Eine siebenj\u00e4hrige Deutsche Dogge wurde in die Klinik f\u00fcr Kleintiere der Tier\u00e4rztlichen Hochschule Hannover aufgrund von Blutungen \u00fcberwiesen. Dort wurde eine H\u00e4mophilie A (Faktor VIII-Aktivit\u00e4t: 4%) diagnostiziert. Um den verantwortlichen Gendefekt f\u00fcr die H\u00e4mophilie bei diesem Patienten identifizieren zu k\u00f6nnen, wurden die kodierenden Regionen und Exon-Intron-Grenzen des caninen Faktor VIII Gens mit Hilfe von Polymerase Kettenreaktion und Elektrophorese analysiert. Kontrollmessungen erfolgten an 25 Deutschen Doggen und jeweils 25 Individuen von drei anderen Rassen. Die Sequenzanalyse von Exon 21 des caninen Faktor VIII Gens identifizierte einen Thymin zu Cytosin Basenaustausch an der Nukleotidposition 6217, welcher einen Austausch von Tryptophan durch Arginin zur Folge hat. Keiner der anderen untersuchten Hunde zeigte die Mutation. Die Analysen mit verschiedenen Proteinmodellen zeigten, dass die ge\u00e4nderte Aminos\u00e4ure in der C1-Dom\u00e4ne des caninen Faktor VIII Proteins lokalisiert ist und eine ver\u00e4nderte Struktur dieses Proteins zur Folge hat. Nach Kenntnis der Autoren ist dies die erste bekannte, f\u00fcr eine H\u00e4mophilie A verantwortliche Mutation des Faktor VIII Gens in einer Deutschen Dogge.<\/p>

Schl\u00fcsselw\u00f6rter:<\/strong>
Gerinnungsst\u00f6rung, Faktor VIII-Aktivit\u00e4t, Mutation, PCR, Proteinmodelle<\/p>","primaryLanguage":"englisch","summary":"A male Great Dane was referred to the Small Animal Clinic, University of Veterinary Medicine Hannover at seven months of age with a known bleeding history. The dog was diagnosed with haemophilia A (factor VIII activity: 4%). To identify the underlying genetic defect responsible for haemophilia in the patient, the coding region and exon-intron boundaries of the canine factor VIII gene were analysed by polymerase chain reaction and electrophoresis. 25 Great Danes and 25 individuals of three different breeds each served as controls. Sequence analysis of exon 21 of the canine FVIII gene of the patient showed a thymine to cytosine nucleotide exchange at nucleotide position 6217, which results in a tryptophan to arginine exchange. None of the remaining dogs studied showed the mutation. Analysis using several protein models demonstrated that the altered amino acid is located in the C1 domain of the canine FVIII protein and results in a change of the protein structure. To the knowledge of the authors, this is the first known mutation of the factor VIII gene in a Great Dane associated with haemophilia A.<\/p>

","keywords":["bleeding disorder","factor VIII activity","mutation","PCR","protein modeling"],"zusammenfassung":"Eine siebenj\u00e4hrige Deutsche Dogge wurde in die Klinik f\u00fcr Kleintiere der Tier\u00e4rztlichen Hochschule Hannover aufgrund von Blutungen \u00fcberwiesen. Dort wurde eine H\u00e4mophilie A (Faktor VIII-Aktivit\u00e4t: 4%) diagnostiziert. Um den verantwortlichen Gendefekt f\u00fcr die H\u00e4mophilie bei diesem Patienten identifizieren zu k\u00f6nnen, wurden die kodierenden Regionen und Exon-Intron-Grenzen des caninen Faktor VIII Gens mit Hilfe von Polymerase Kettenreaktion und Elektrophorese analysiert. Kontrollmessungen erfolgten an 25 Deutschen Doggen und jeweils 25 Individuen von drei anderen Rassen. Die Sequenzanalyse von Exon 21 des caninen Faktor VIII Gens identifizierte einen Thymin zu Cytosin Basenaustausch an der Nukleotidposition 6217, welcher einen Austausch von Tryptophan durch Arginin zur Folge hat. Keiner der anderen untersuchten Hunde zeigte die Mutation. Die Analysen mit verschiedenen Proteinmodellen zeigten, dass die ge\u00e4nderte Aminos\u00e4ure in der C1-Dom\u00e4ne des caninen Faktor VIII Proteins lokalisiert ist und eine ver\u00e4nderte Struktur dieses Proteins zur Folge hat. Nach Kenntnis der Autoren ist dies die erste bekannte, f\u00fcr eine H\u00e4mophilie A verantwortliche Mutation des Faktor VIII Gens in einer Deutschen Dogge.<\/p>

","schluesselwoerter":["Gerinnungsst\u00f6rung","Faktor VIII-Aktivit\u00e4t","Mutation","PCR","Proteinmodelle"],"translatedTitle":"Canine H\u00e4mophilie A bei einer Deutschen Dogge, verursacht durch einen Thymin zu Cytosin Nukleotidaustausch an der Nukleotidposition 6217","abstractE":"A male Great Dane was referred to the Small Animal Clinic, University of Veterinary Medicine Hannover at seven months of age with a known bleeding history. The dog was diagnosed with haemophilia A (factor VIII activity: 4%). To identify the underlying genetic defect responsible for haemophilia in the patient, the coding region and exon-intron boundaries of the canine factor VIII gene were analysed by polymerase chain reaction and electrophoresis. 25 Great Danes and 25 individuals of three different breeds each served as controls. Sequence analysis of exon 21 of the canine FVIII gene of the patient showed a thymine to cytosine nucleotide exchange at nucleotide position 6217, which results in a tryptophan to arginine exchange. None of the remaining dogs studied showed the mutation. Analysis using several protein models demonstrated that the altered amino acid is located in the C1 domain of the canine FVIII protein and results in a change of the protein structure. To the knowledge of the authors, this is the first known mutation of the factor VIII gene in a Great Dane associated with haemophilia A.","date":{"year":2017,"date":"03\/2017","accepted":"2017-03-07"},"volume":"2017","openAccess":false,"journal":"Berliner und M\u00fcnchener Tier\u00e4rztliche Wochenschrift","titleImageId":944,"pages":"","redirects":["canine-haemophilia-a-caused-by-a-thymine-to-cytosine-nucleotide-exchange-at-nucleotide-position-6217-in-a-great-dane\/150\/3130\/101188"],"tierartCategories":[],"artikelartCategories":["Tier\u00e4rztliche Wochenschrift","Abostufe BMTW","Fachartikel"]} %8 03/2017