CP+Data+Analysis

The MEGA alignment performed on the gene sequences showed a high degree of similarity between the sequences as indicated by the numerous stars found throughout the alignment (Figure 1). This suggests that the Muscle alignment was strong and that the AP4E1 gene sequence is similar to those of the other species examined. After producing the UPGMA phylogenetic tree, it was found that there were no bootstrap values below 70 (Figure 2). This means that the tree produced is statistically significant and can be used to interpret the results. The results indicate that each species' gene is genetically distinct from one another, as expected, but that they are all very similar as well. Because the bootstrap values are high, it is clear that the AP4E1 gene is conserved among the species examined. It also supports the hypothesis that the AP4E1 gene is highly conserved among other species that were not examined during this particular research.
 * Phylogenetic Analysis **

The protein analysis is very similar to that of the gene analysis. The MEGA alignment performed on the protein sequences also showed a high degree of similarity, with only a few gaps throughout the entire alignment (Figure 3). The alignment was strong and showed that the protein sequences used were all very similar to each other. After producing the Maximum Parsimony phylogenetic tree, once again there were no bootstrap values below 70 (Figure 4). Therefore, the protein tree was also considered statistically significant and was used for interpretation. The species' proteins are all genetically distinct from each other and are highly conserved.

Some relationships between species were also determined through the interpretation of the gene and protein phylogenetic trees (Figures 2 & 4). In both cases the Human sequences were most closely associated with the Sumatran Orangutan's sequences. This indicates that the Human and Orangutan's AP4E1 gene and proteins are most closely related. After that, the Marmoset was found to be the next most closely related specie to the Human and Orangutan.

** PDB and STRING Analysis ** The PDB tool was used mainly for examining the protein structure of AP4E1 (Figure 6). It is important to understand a protein's structure in order to fully understand its function. After looking at the 3D structure of the AP4E1 protein, a better understanding of the protein itself and the way it can interact with other proteins was developed.

Using the STRING tool, an interactive protein map was produced looking at the AP4E1 protein (Figure 5). The "confidence view" of the STRING tool was used to examine the strength of the association of the AP4E1 protein with other proteins. The strength of the interactions was depicted using thicker lines. It was found that the AP4E1 protein interacts with and is most closely associated with other AP-4 family proteins. The AP4E1 protein had the strongest association with the AP4S1, AP4M1, and AP4B1 proteins as depicted by the thicker blue lines connecting them. These results indicate that the AP-4 family proteins work very closely with each other and are associated very strongly with one another. This only supports further the idea that a disruption in one of the AP-4 subunits will have detrimental effects on the entire system in which it is a part of. Because the AP-4 family plays such a large role in the nervous system of a developing body, a disruption in the AP4E1 protein could greatly effect the functioning of its other family members and of the entire pathway in which it is involved, and result in an individual having intellectual disorders, like Cerebral Palsy.

** Research Conclusions ** Cerebral Palsy, depending on the severity, can greatly affect an individual's life in all aspects; it may affect learning abilities, employment/housing opportunities, or even the length of life. Even though CP is caused by a damage and is considered non-progressive, the secondary conditions that arise from CP make the condition a progressive one. The permanent neurological damage in an individual with severe CP compromises many motor functions like mobility and balance (Peterson, M. D., et al., 2012). The most common secondary condition found in patients with CP is muscle spasticity. As a result, muscle function and muscle use are greatly decreased in patients. This eventually leads to muscle degradation and muscle deformity (Gough, M. & Shortland, A. P., 2012). This alone typically requires many therapies and surgeries to correct, taking a great toll on the body of an individual with CP. Therefore, the damage done to the brain of a patient with severe CP may be static, but the symptoms and secondary effects of the condition can essentially turn the condition into a progressive one.

The research and data done enhance the hypothesis that some types of CP may be a result of genetic damage, specifically to the AP4E1 gene. Damage to the brain is a key characteristic of the CP disorder, but there is evidence to suggest that the damage does not necessarily have to be physical. A sickness, or complications during the labor/delivery of a child may not be the only way CP can arise. The primary research done on an autosomal recessive type of CP supplies evidence that the AP4E1 gene can play a significant role in the development of CP. Not only could the gene enhance the severity of the symptoms seen in someone with CP, but it may actually cause the disorder in some cases (Jamra, R. A., et al., 2011). It is also found that the AP4E1 gene is conserved among various species, indicating that the same disruption or mutation of the gene in another species may result in a harmful condition.

** What's Next? ** As science progresses, researchers are expecting to be able to better understand Cerebral Palsy's etiology. As of right now, the mechanism by which the different types of CP arise is still fairly unclear. Because CP is a chronic condition, it cannot be cured, so the focus continues to be on producing better therapies and treatments targeted at decelerating the harmful secondary conditions, like muscle spasticity. Studies have been conducted examining the effects of osteopathic manipulative treatment (OMT) that may improve function and overall quality of life for CP children. OMT is hands-on care that includes specific movement of muscles and joints aimed at relaxing and stretching certain parts of the body (Duncan, B., et al., 2008). Different types of OMT are currently being studied and should continue to be studied if improvement in function is shown. While at this point there is no cure, researchers are actively seeking new therapies and treatments that will help individuals suffering from CP.

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