The Maine Coon cat originates from the north east of the USA and belongs to most famous breeds in the world. This semi-long hair cat is one of the largest domestic cats worldwide. It can reach a weight from four to nine kilogram and a length up to 1.20 meters. Since 1983 it has been accepted in the last breeder foundation and has been a full-fledged pedigree cat.
During their breeding history typical hereditary diseases occurred. Most of these diseases contain the Hypertrophic cardiomyopathy and the spinal muscle atrophy which is a disease of motor neurons. But this comprises only a little part of all diseases.
Most common genetic heart disease which occurs in cats as well as in human beings is the Hypertrophic cardiomyopathy (HCM). It often leads to thrombo-genesis, heart failure or to a sudden cardiac death.
HCM is bequeathed autosomal dominant and more than 60% of cats are affected. There are already over 450 known mutations in 20 sarcomere related genes in human beings which lead to Hypertrophic cardiomyopathy. Currently it is a non-curable disease but there are efficient treatment possibilities if it is diagnosed in its early stages. HCM can be detected by clinical examinations and echocardiography. For examination the cats lay in lateral recumbence, on the left side as well as on the right side. At the same time the end diastolic left ventricular wall thickness and the interventricular septum are measured. The phenotype is positive if the left end diastolic wall thickness measures more than six millimeters. (Meurs et al, 2005) This leads to a higher left atrial pressure and a lower blood volume. Further symptoms are thickness of papillary muscles and a forward movement of the mitral valve. For a long time it was assumed that there are genetic defects on the sarcomere related genes. Frequently it is about point mutations that apply sarcomere proteins like myosin, myomesin, troponin C, T and I. Point mutations are thought to lead to amino acid changes and most likely lead to protein changes. Scientists believed that mutations, which lead to HCM in human beings, might also exist in cats. In cats especially two mutations called A74T and A31P polymorphisms, special gene sequences on the myosin binding protein C3 gene (MYBPC3) probably result in HCM. 34% of Maine Coon cats worldwide hold the A31P polymorphism. The A31P polymorphism has a base pair change from guanine to cytosine at the 31st codon in exon three and therefore alanine changes into proline. According to first published studies this can lead to a reduction of myomesin, an m-band protein, and MYBPC3 itself which was detected by a lower staining of immunofluorescence. Myomesin is important for developing the exact thickness of filaments and septum. Homologous sequences with point mutations were not only found in Maine Coon cats but also in Ragdoll cats, where they were located in a different place. (Meurs et al, 2005)
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There is heterogeneity between phenotype and genotype, which corresponds to the degree of effectiveness of mutations on the disease. Consequently, a cat can be genetically ill but phenotypically healthy. In earlier studies from Ohio a connection was detected between mutation and disease. It was pointed out that genotype positive cats develop Hypertrophic cardiomyopathy more often than genotype negative cats. As a result scientists developed a test to confirm the disease due to its genetic basis. Many commercial laboratories provide it nowadays. The test says if one polymorphism is detected, the genotype is positive. In 2010 a German study by Wess et al. controlled this assumption. The exonic regions of the Myosin binding protein C3 gene were amplified with a poly chain reaction (PCR) and sequences were analyzed. Then the sequences were compared for probable base pair changes and protein changes which were detected with SDS- PAGE and PolyPhen.
In this study 22% of all Maine Coon cats were tested genotype positive for the A31P polymorphism, whereas in reality 83% of them certainly are phenotypic healthy. Effectively only 17% of genotype positive cats are ill. One cat of them is bequeathed homozygous, the others are bequeathed heterozygous. This means that the outcome of the disease does not depend on this kind of inheritance. It is assumed, that homozygous cats are even more affected than heterozygous cats, but it is not a lethal factor. Whether a mutation is bequeathed heterozygous or homozygous is determined by sequencing. This applies also the other way round: There were some ill cats of all genotype negative cats. The same was found for the A74T polymorphism. It was also found out that the change from guanine to cytosine results only in begin protein changes, which do not affect the protein in a bad way, wherefore there is no damage in the proteins (Wess et al, 2010). This contrasts a study concerning human beings, where this kind of mutation leads to a malign protein change. This means that no mutations are detected which include all of the following criteria. The mutation is existent only in affected cats, but not in healthy ones; it always has amino acid changes and the mutation is connected with a change of polarity of amino acids. After all it was described that there is no association between phenotype and genotype in cats, which is different from human beings. Consequently, this mutation cannot be the only reason for the outbreak of the disease. It is likely that there are interactions between further mutations and the A31P polymorphism. It can also not be excluded that there are other mutations in promotor or untranslated regions. The number of mutations might be associated with the phenotype and the outbreak of the disease. If for example one cat has four different mutations and the other one has only one mutation, it is likely that the cat which has four mutations gets the disease sooner.
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Because of this heterogeneity a negative test result cannot eliminate the possibility that a genotype negative cat has HCM or will not develop it later in life. The sensitivities for this test with 0.25 and 0.08 for both polymorphisms are very low; therefore the validity is not satisfactory.
In 2005 the A31P mutation was first detected by Meurs et al. It was found in phenotype positive Maine Coon cats, which had an age of 24 to 36 months. To avoid mistakes scientists take mostly elderly cats for their studies. Therefore scientists and breeders cannot determine for sure that a phenotype negative cat will not develop HMC in the future. But scientists in later studies think it is improbable because most examined cats had an average age of 65 months. The reason for the differences between the studies could be that of deceased genetic variability because the cats of the Ohio study came from the USA and the cats of the German study were mostly from Germany, Switzerland and Austria. Admittedly, the degree of relationship barley deviates, because the import of these cats from the USA to Germany has not stopped yet and therefore there is still a genetic exchange. The prevalence of homozygous and heterozygous cats is nearly identical in each country. Accordingly the German study is also representative worldwide. (Wess et al, 2010) Nevertheless, for further analysis a long-term study is commendable in order to solve the age problem.
Summed up, it can be said that the A31P and the A74T polymorphisms are not the only reasons for the Hypertrophic cardiomyopathy and thus further mutations which have an effect on the outcome of disease must be there. Correspondingly the genetic test cannot be significant and therefore test results do not necessarily demonstrate if a cat is healthy or ill. Consequently, breeders should not believe the test results. The best option for them is to take the echocardiographic examinations periodically.
In spite of the called results there is still a contingent association of these polymorphisms, which is also relative to other mutations, thus scientists have to perform more research on this area.
B.Sc Biology, 5.Semester, 2684100