Results+of+Genomics+of+Cystic+Fibrosis

__Results-continued __
Cystic Fibrosis occurs when a person receives two mutated CFTR genes from both their mother and father. This disease is most common among the white population, which occurs within every 1 in 2,500 to 3,500 white newborns. There have been well over a thousand mutations found in this specific gene alone. The human CFTR gene is located on the long arm of chromosome 7 and is quite large at about 189kb in length (1,480 amino acids), making there a lot of room for variation. Among the many mutations, the most common are ΔF508, G542X, G551D, N1303K, and W1282X.

With so many possible mutations, there are a lot of phenotypes that result. Most complications are present in the lungs and pancreas but can also been experienced elsewhere in the body. Cystic fibrosis patients will usually experience symptoms of excessive mucus buildup in the lungs and airways that result in reoccurring bacterial infections that eventually lead to damage of the respiratory system that can progress to respiratory failure. Many treatment and therapy options are available, such as, airway clearance therapies and inhaled medication being among the most used. Since patients typically deal with reoccurring bacterial infections, maybe kinds of antibiotics are also prescribed by physicians.

Many studies research to develop new, more efficient treatment and therapy options that could work better to help increase the lifespan of cystic fibrosis patients. Techniques like CRISPR/Cas9 and stem cell correction research are being used to find a potential correction of this genetic disease. These techniques are still in very initial stages, but could show a promising future in cystic fibrosis research.

Scientists have the ability to use comparative genomics to better understand the conservation of the CFTR gene within various species. It was apparent that between a selected few species, the CFTR gene was highly conserved and experienced very minimal evolutionary variation between species.

**Figure 6**. Human CFTR Crystalized Protein Structure (Image retrieved from RCSB The Protein Databank, []).

**__Discussion __**
Cystic Fibrosis is a disease that occurs when there is a point mutation present in the gene encoding the cystic fibrosis transmembrane conductance regulator. The CFTR gene provides the instructions for the making of the ABC transporter-class chloride ion channel, which is responsible for transporting negatively charged chloride ions into and out of cells. The channel's main function is to allow water and chloride ions to flow through the channel to help control the movement of water in tissues. This water movement is essential for the production of thin, freely flowing mucus. A normal functioning CFTR channel would result with the movement of chloride ions out of the cell along with water molecules. This channel has four serine amino acids contained in it, which get phosphorylated by the cyclic adenosine monophosphate (cAMP) dependent protein, serine kinase. This mechanism is dependent on whether or not a peptide hormone is detected by a receptor at the membrane of a cell. The pumping of this channel will not occur unless it is phosphorylated at all four of its serine sites.

Due to the size of the CFTR gene, there have been hundreds of documented mutations in the gene in humans, indicating high variation that can result with several phenotypes. Most of these mutations are found to change single amino acids in the CFTR protein or delete a small fragment of DNA from the CFTR gene. The most common mutation, ΔF508, is a deletion of the amino acid at position 508 in the CFTR protein which results with the immediate breakdown of the abnormal channel, meaning it will never reach the cell membrane for chortled ion transport. Any mutation in the CFTR gene would cause dysfunction in the chloride ion channel function, thus not allowing any flow of chloride ions or water across the cell membrane, (Tayoun, et al., 2013).

Due to so many mutations that can occur in the CFTR gene, there are many phenotypes that a patient can experience. Many treatment and therapy options work to reduce mucus in the airways to allow the patient to breath easier and feel less discomfort. Mucolytic mediations, for example, work to thin mucus and allow a patient to cough it up easier. These kinds of treatments also work to prevent future bacterial infections that are very common in cystic fibrosis patients. Since the environment in the lungs is coated with mucus, more unique bacteria tend to grow and cause infection. This leads to physicians having to prescribe less common antibiotics that work on these specific bacteria.

Comparative genomic research was used to determine the conservation of the CFTR gene within variously selected species. It was determined that the gene was rather conserved, which indicates high importance in this gene. Again, the CFTR gene codes for the chloride ion channel that is responsible for exporting chloride ions and water into and out of epithelial cells. It is used in many biochemical pathways and plays an important role in regulation.

A lot of research using future technology is leading scientists to a possible cure for cystic fibrosis. These technologies include CRISPR/Cas9 and stem cells correction research. CRISPR/Cas9 is a genome editing system that seeks correction of harmful or undesired mutations in genes. In a study performed at the University Medical Center Utrecht in The Netherlands CRISPR/Cas9 system was used to correct the CFTR locus using homologous recombination in previously culture intestinal stem cells of known cystic fibrosis patients. This corrected allele’s function was measured to be fully expressed and functional in clonally expanded organoids. Studies such as this provide great evidence of gene correction utilizing adult stem cells. It is important to understand that this type of technology does not cure cystic fibrosis, but rather provides a very initial start in understanding gene editing in very basis systems. Technology as powerful as this would require many years of research and trialing in order to be fully functional in a human model. Many similar studies have been developed using this same combination of CRISPR/cas9 and stem cell research. This technology is the future and is the possible solution for the unimaginable.

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