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Orientador: Alexandre Secorun Borges / Resumo: A principal causa de miotonia não distrófica hereditária ocorre devido à mutações no gene CLCN1, codificante para a proteína CLC1 que forma o canal iônico seletivo para o íon cloreto predominante no tecido muscular esquelético. Mutações no gene CLCN1 foram descritas como causadoras de miotomia hereditária em humanos e em várias espécies animais. Não existe descrição de miotonia hereditária na espécie suína. O objetivo deste estudo foi realizar a caracterização clínica e molecular de uma forma de miotonia hereditária em suínos. A hipótese desse estudo foi que animais com sinais clínicos compatíveis apresentavam a miotonia hereditária. Esses animais foram avaliados sob aspectos clínicos, eletromiográficos, histopatológicos e moleculares. Os sinais clínicos verificados foram hipertrofia e rigidez musculares, miotonia com startle response formação de dimples e fenômeno warm-up evidentes. Não foi constatada distrofia muscular ao exame histopatológico. Ao exame eletromiográfico foram demonstradas descargas miotônicas clássicas com formação de som característico diver bomb. A nível molecular foi verificada a ausência dos nucleotídeos referentes aos éxons 15 e 16 utilizando amostras de cDNA dos animais afetados. No DNA genômico foi encontrada uma grande deleção de 4165pb (g. NC_010460.4 del 6912538_6916702) na região do gene CLCN1. Análises de expressão relativa demonstraram níveis de expressão em tecido muscular de animais wild type para um transcrito associado a miotonia hereditári... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The major cause of hereditary non-dystrophic myotonia occurs due to mutations in the CLCN1 gene, coding for the CLC1 protein that forms the ionic channel selective for the predominant chloride ion in skeletal muscle tissue. The resulting hereditary disease is called congenital myotonia in human medicine. Mutations in the CLCN1 gene have been described as causing hereditary myotomy in several animal species, but in the swine species, no mutation in this gene has been described. The objective of this study was to perform the clinical and molecular characterization of hereditary myotonia in swine. The hypothesis of this study was that animals with compatible clinical signs had hereditary myotonia. These animals were evaluated under clinical, electromyographic, histopathological and molecular aspects. The clinical signs verifed were muscular hypertrophy and stifness, myotonia with startle response and formation of dimples. The phenomenon warm-up was evident. No muscular dystrophy was observed at the histopathological examination. Electromyographic examination showed classic myotonic discharges with characteristic sound. At the molecular level, the absence of nucleotides from exons 15 and 16 was verifed using cDNA samples of afected animals. In genomic DNA a large deletion of 4165bp (g NC_010460.4 del 6912538_6916702) was found in the region of the CLCN1 gene. Relative expression analyzes demonstrated expression levels of wild type animals for a transcript associated with heredita... (Complete abstract click electronic access below) / Doutor

Progressive rod-cone degeneration (PRCD) is the late form of progressive retinal atrophy (PRA). It is an autosomal recessive hereditary retinal defect. This disease in dogs is consistent with one form of retinitis pigmentosa (RP) in humans. Phenotypic manifestations are identical and it is known to be an identical causal mutation. A study of this defect in dogs could also explain a lot in human medicine. The gene for PRCD was mapped in the region of centromer of the canine chromosome 9 (CFA9). In this thesis, genotyping of 120 dogs of different breeds and age was performed. Most represented a breed of English Cocker Spaniel which is predisposed to the disease. Analysis PRA-PRCD was performed by molecular genetic methods PCR-RFLP and the horizontal agarose electrophoresis. Genotypes were determined on the basis of different fragment lengths. The normal allele was 396 bp in length and the mutated allele had a length of 116 bp. Presence of mutated allele was only detected in 25 heterozygotes carriers which were usually breeds with this predisposition. Frequency of the mutated allele was 10.4 %. In the selected population 20.8 % of heterozygotes were represented. The results of the study show approximately one fifth of the tested dogs are heterozygous carriers. Findings of other studies confirm there are generally more heterozygotes than homozygotes in which the disease is manifested during life. However, if this fact is not clearly taken in consideration, the number of sick dogs can rapidly increase during short period of time. In the future, it would be appropriate to adopt measures which would definitely eliminate the occurrence of the mutated allele. These measures could include genetic tests that reliably reveal hidden carriers (heterozygotes) in predisposing breeds. Heterozygotes may increase the representation of this allele in the population. This leads to an increase in the number of diseased animals.

Ziel der vorliegenden Arbeit war die Erstellung einer Übersicht über alle monogenen Erbkrankheiten und -Merkmale bei Hunden, deren molekulargenetische Ursachen bisher (Stand: Oktober 2007) identifiziert werden konnten. Ein besonderer Schwerpunkt lag dabei auf der Darstellung der verfügbaren Genotypisierungsmethoden.Im Vergleich zu anderen Spezies herrscht auf dem Gebiet der Genomanalyse bei Hunden eine auffallend hohe Forschungsaktivität. Die erste Kopplungskarte wurde 1997 veröffentlicht und ist seitdem stetig erweitert worden. Seit 2001 steht eine integrierte Kopplungskarte zu Verfügung. Ein weiterer Meilenstein war die erste Assemblierung der Sequenz des gesamten caninen Genoms CanFam1.0 im Juli 2004. Seit Mai 2005 ist eine überarbeitete Version (CanFam2.0, Mai 2005) verfügbar. Das große Interesse an der Spezies Canis familiaris in diesem Zusammenhang ist vor allem durch die besondere Eignung des Hundes als Modelltier für humane Erbkrankheiten und -merkmale begründet. Die relativ starke Inzucht innerhalb von Rassen führt zum Auftreten zahlreicher monogener Erbkrankheiten, die phänotypisch und, wie die Forschungsergebnisse der letzten Jahre zeigen, häufig auch genotypisch homolog zu Erkrankungen des Menschen sind. Die Zahl der beim Hund im Zusammenhang mit Erbkrankheiten oder bestimmten morphologischen Merkmalen identifizierten Genmutationen ist in den letzten Jahren rapide angestiegen.Die Nutzung der ständig wachsenden Menge an Daten, die sich aus der beschriebenen Entwicklung ergeben, ist nicht nur für die humanmedizinische Forschung von Interesse, sondern bietet Hundezüchtern die Möglichkeit, über den Einsatz molekulargenetischer Genotypisierungsmethoden mit einer hohen Effizienz gegen Erbkrankheiten und unerwünschte morphologische Merkmale zu selektieren.Inzwischen konnten 86 pathogene Mutationen in 64 Genen als Ursache für bestimmte canine Erbkrankheiten identifiziert werden. Für 66 Mutationen sind DNA-Tests etabliert worden. Ein weiterer DNA-Test zum Nachweis einer pathogenen Mutation beruht auf der Assoziation eines Haplotyps mit der nachzuweisenden Erkrankung. Außerdem sind neun Polymorphismen in fünf Genen beschrieben worden, die mit bestimmten Farbvarianten des Fells und der Nase assoziiert sind. Für sieben dieser Polymorphismen sind DNA-Tests entwickelt worden. (Stand: Oktober 2007)Trotz zahlreicher Quellen (OMIA, Liste der Universität Bern: Gentests beim Hund , Internetseiten verschiedener Firmen und Einrichtungen, die Gentests anbieten und Patentschriften) sind die wesentlichen Detailinformationen oft erst nach längerem Suchen auffindbar. Die vorliegende Arbeit bietet die Grundlage für die Erstellung eines Handbuches, um Tierärzten und Hundezüchtern den Zugang zu verfügbaren DNA-Tests bei Hunden zu erleichtern.