Test Design For Oculopharyngeal Muscular Dystrophy Essay — страница 4

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case, blue colonies will need to appear when the gene that is fused to the gene encoding for Gal4 BD is the wild-type form of PABP2. CONCLUSION: These binding experiments will greatly enhance the understanding of OPMD. They will find potential proteins which act downstream of the mutated PABP2, causing the continual disintegration of muscle tissue over time. Indeed, as mentioned before, sequencing, PCR, or restriction analysis of the elucidated mutant PABP2-binding proteins will need to be performed in order to characterize them. Also, point mutation studies of the genes encoding these proteins can help find regions that are essential for its function. Experiments involving mRNA expression can be done to see if these proteins are expressed in various muscle cells of normal vs.

diseased individuals. This can also be achieved by in situ hybridization using raised antibodies for the protein. Of course, even more binding experiments can be performed on these extended poly-A and mutant PABP2-binding proteins using methods already described. In addition, a future experiment can be to screen for compounds that can directly affect the gene defects by, for example, destabilizing the DNA structure that forms with the extra repeat. Somewhere down the road, for genetic disorders of muscle, lies the prospect of gene therapy. . Today, there has not yet been a single published report of a patient who was helped by gene therapy. These different experiments may someday propel the prospect of gene therapy for not only OPMD but for other genetic disorders of muscles.

However, it will be a difficult task due to the problem of intractability of muscle as a tissue (ie. difficult to reach each individual fibre or even enough of them to make a difference). Main problems of all muscular dystrophy disorders about how to get the correct version of a gene, with all its controlling elements, into muscle tissue remain to be solved. TABLE 1: Expected results for the possible outcome of protein binding leading to OPMD using affinity chromatography experiments. The +’s represent protein binding activity and -’s represent lack of protein binding. The number of +’s illustrate the amount of bound proteins. 6 7 8 9 10 11 12 13 14 Smooth – - – - – - – - - Eye – ++ +++ ++++ +++++ +++++ + +++++ ++ +++++ +++ +++++ ++++ Throat – ++ +++ ++++ +++++

+++++ + +++++ ++ +++++ +++ +++++ ++++ Leg – + ++ ++ ++ +++ +++ +++ +++ Hip – + ++ ++ ++ +++ +++ +++ +++ Shoulder – + ++ ++ ++ +++ +++ +++ +++ TABLE 2: Expected results for the possible outcome of the lack of protein binding leading to OPMD using affinity chromatography experiments. The +’s represent protein binding and the -’s represent lack of protein binding. The number of +’s illustrate the amount of bound proteins. 6 7 8 9 10 11 12 13 14 Smooth +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ +++++ Eye +++++ +++++ +++++ +++ +++++ ++ +++++ + +++++ ++++ +++ ++ + Throat +++++ +++++ +++++ +++ +++++ ++ +++++ + +++++ ++++ +++ ++ + Leg +++++ +++++ +++++ ++++ +++++ ++++ +++++ ++++ +++++ +++ +++++ +++ +++++ ++ +++++ ++

+++++ + Hip +++++ +++++ +++++ ++++ +++++ ++++ +++++ ++++ +++++ +++ +++++ +++ +++++ ++ +++++ ++ +++++ + Shoulder +++++ +++++ +++++ ++++ +++++ ++++ +++++ ++++ +++++ +++ +++++ +++ +++++ ++ +++++ ++ +++++ + REFERENCES: Brais, B.; Bouchard, J.; Rochefort, D.L.; Chretien, N; Tome, F.; Lafreniere, R.; Rommens, J; Uyama, E.; Nohira, O.; Blumen, S.; Korcyn, A.D.; Heutink, P; Mathieu, J; Duranceau, A.; Codere, F.; Fardeau, M.; Rouleau, G.A. (1998) Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nature Genet, 18: pp164-167. Fried, K.; Arlozorov, A.; Spria, R. (1975) Autosomal recessive oculopharyngeal muscular dystrophy. J. Med. Genet. 12: pp416-418. LaFontaine, G. (Feb 24, 1996) Quebec’s common muscular dystrophy gene mutation found. Medical Post: pp20.

MDA Publications (http://www.mdausa.org/publications/Quest/q5resup.html) (Feb. 1998) Research Updates. Quest vol.5, number 1. Rifugo, G. et al. (1997) Survey of maximum CTG/CAG repeat lengths in human and non-human primates: Total genome scan in population using the Repeat Extension Detection method. Human Molecular Genetics 6:3 pp403-408. 36b