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HGDP Selection Browser

This image, taken from the HGDP browser, shows all the genotypes SNPs associated with the FBN1 gene. Each SNP has a different manifestation, whether it is a classical case of MFS, or an undetectable phenotype. Although there is no specific SNP that results in Marfan syndrome, many of these attribute to the physical aspects of the disease. Additionally, more SNPs could be discovered in the future, as this is only an image of the genotyped SNPs on the FBN1 gene (FBN1 Region, 2015).

SNPs of the FBN1 gene Image taken from HGDP Selection Browser

This image, taken by selecting the rs7165060 SNP, shows where the variant is most common in the world. The blue represents the original "ancestral" allele, and the orange represents the mutated allele for this location. The European continent seems to be hardly affected by the SNP, while the most affected areas are in Eastern Asia, northern Mexico, and some Pacific Islands. Since this map is specific only to this allele, it should not be used for the prediction of any other SNP of FBN1. Many of the other SNPs reveal a very distribution pattern, contrary to this (FBN1 Region, 2015). Ancestral versus Derived allele of the SNP rs7165060 Image taken from HGDP Selection Browser

This image below is a depiction of the different FBN1 mutation around the world. The topmost line represents south Asia, where we know from the previous image has the highest incidence of SNPs. It is unclear as to why the Southeast Asian continent has such a high prevalence of SNPs. This image, unlike the map above, shows the collective SNPs of the FBN1 gene, as opposed to one SNP alone. However, we can still see that the Asian continent has the highest amount of SNPs of the FBN1 gene. Towards the middle of the chart, the European (orange lines) and Middle Eastern (blue lines) continents also have a high number of SNPs present in their populations. Below these lines, the Americas (yellow) and African (red) lines show a much lower incidence of SNPs. Where this graph differs from the map above is the prevalence in the East Asian SNPs. In the map above, the East Asian populations have a very high incidence of the SNP, but the chart below shows one of the lowest incidences. This can be attributed to the fact that the map above only represents one SNP, while the chart below represents all SNPs of the FBN1 gene (FBN1 Region, 2015). Comparison of SNPs on each continent Image Taken From HGDP Selection Browser

Protein Data Bank

Fibrillin-1 Protein Image taken from the Protein Data Bank

This is a 3 dimensional image of the protein fibrillin-1. As seen from the image, it is an extremely complex protein with many terminals and functions. Any damage to the formation of this protein leads to the disastrous effects of Marfan Syndrome. Since this protein is such an integral structural protein, the damage caused by the mutated gene responsible for it's production is extremely dangerous. Although it is unable to be seen from this image, the protein is mainly made up of beta pleated sheets. There is a very small number of alpha helices present in the composition of this protein (Yadin, et al., 2016).

Comparative Toxicogenomics Database

The results from this database show a wide variety of interacting chemicals, drugs, and affected pathways.

<span style="font-family: Georgia,serif; font-size: 120%;">The main interactions of the FBN1 gene and pharmaceuticals revolved around anti-hypertensive medications. What is interesting about this interaction is the fact that many patients who have MFS need to be prescribed high blood pressure medications, due to the high incidence of aneurisms and other cardiovascular problems. High blood pressure medications can reduce the probability of the aneurism rupturing, or the aorta shredding. The interaction between the FBN1 gene and the medication causes a decreased expression of the FBN1 mRNA, which causes less of the fibrillin protein to be produced (Chemical, 2016).

<span style="font-family: Georgia,serif; font-size: 120%;">The main pathway that the FBN1 gene is a part of is the extracellular matrix organization. This pathway is responsible for the makeup of connective tissue and the environment of cells. It is mainly composed of microfibrils, collagen, elastin, and other connective tissues. Since microfibrils are such a large part of this organization, any damage to the gene responsible for its makeup will cause problems in the connective tissue. Collagen is made up of microfibrils,and is responsible for providing elasticity and strength to the connective tissues. Once again, microfibrils are the main source of the organization. Since collagen is important to the makeup of cartilage, tendons, tissues, and bones, the damage caused by a mutated FBN1 gene ripples through and causes all the manifestations of MFS (S., Jupe, 2013).

<span style="color: #4962c3; display: block; font-family: Georgia,serif; font-size: 200%; text-align: center;">Ensembl <span style="font-family: Georgia,serif; font-size: 120%;">Information regarding the FBN1 gene shows that it is an important component of integrin binding, calcium binding, protein binding, and also responsible for the elasticity of the extracellular matrix. This reinforces the idea that the FBN1 gene is highly important regarding the structural integrity of all the connective tissue. The gene also plays an important role in the development of humans from the time of conception. FBN1 is responsible for skeletal, renal, cardiac, and ocular development. This explains why these four systems are the most affected in patients suffering from MFS. Additionally, the gene is extremely active during fetal development, which can also explain cases of neonatal MFS. Another biological role is the binding of transforming growth factor beta. This is a crucial component, since the manifestation of MFS surrounds the fact that mutated fibrillin proteins cannot bind enough growth factor to support a normal growth period. Without the adequate amount of growth factor bound, the individual is seen with the elongated limbs, fingers, and face that is a symptom of the disease (Ensembl, 2016).

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