Problem Summary 1: Cystic Fibrosis
Cystic Fibrosis (or CF) is a genetic disorder that affects ion movement through the plasma membranes of some organs (Karp, 2010). CF usually ends up causing a build up of mucus in the lungs which interferes with the lungs' main functions, breathing and removing bacteria, and eventually causes death at an early age (Karp, 2010). An estimated 1 in 2500 infants in the Caucasian population will be born with CF (Karp, 2010). In this essay, I will explain how CF arises in patients and how it causes these deteriorating effects on the lungs. I will also talk about current and potential CF treatments and their risks on the affected individual and the society.
CF is caused by a defect in the genes that transcribes the protein Cystic Fibrosis Transmembrane Conductance Regulator (or CFTR) (Karp, 2010). CFTR allows water to pass to the lungs (Karp, 2010). There are many mutations to the CFTR that causes CF to develop, but the most common mutation is called delta-F508 (DF508) (Karp, 2010). DF508 is a deletion (D) of a phenylalanine (F) at location 508 of the CFTR (Karp, 2010). This deletion, among others, causes the lung cells to stop supplying the lungs with water, thus causing dehydration (Karp, 2010).
CFTR hydrates the lungs by transporting chloride ions to the outside of the epithelial cells. Water transport is activated by osmosis across the generated ion gradient (Karp, 2010). This hydrates the lungs, allowing mucus (and bacteria) to be swept outside of the lungs (Karp, 2010). However, since CF is hereditary, if both CFTR genes translates to a defected CFTR protein in an individual, that patient will develop CF (Hartwell, 2008). On the other hand, if only one CFTR gene translates to a defected CFTR protein, then the other gene will be able to supply enough CFTR proteins to prevent CF from occurring (Hartwell, 2008). However, since water transport is dependent on the concentration gradient across the plasma membrane, this gradient must be maintained to ensure hydration of lungs. If the other CFTR gene defects do not cause a complete loss of the protein or its function, then, theoretically, a mild form of CF could be observed depending on the rate of chloride ion transportation (Hartwell, 2008). The chances of such an incident is extremely small, considering that there are a lot of mutations and not all of them have such an effect.
The different mutations in the CFTR gene could cause different affinities for the chloride ion in the protein, thus slowing down its passage outside of the cell. Some mutations could be severe enough to block all ion transport activity and hence result in loss of function. In CF patients with DF508, the mutation disrupts the endoplasmic reticulum's function in processing this protein (Karp, 2010). This causes the mutated CFTR to be destroyed and the lung epithelial cells to lack CFTR in their plasma membranes (Karp, 2010). Without the CFTR, water cannot flow in adequate amounts into the lungs, thus causing the thick mucus to develop on the lining of the epithelial cells (Karp, 2010). However, certain treatments can help reduce the effects of CF.
There are various methods to treat CF, but the results show very little success. Some treatments include inhaling certain molecules, like mannitol, to allow more water to leave the epithelial cells (Karp, 2010). Another option is a lung transplant. A lung transplant is not a very good option, since there are many complications to it. Removing a lung from a donor necessarily means that the donor will die, so rarely do people donate their lungs, unless they are terminally ill. Also, there are certain type compatibility between organs of donors and bodies of recipients, which applies to lungs (Freeman, 2008). One more issue is that CF is prevalent in an affected individual from birth; finding a lung with the right size reduces the chances of lung transplant even further.
With more information and data discovered about CF and CFTR, it is possible to find an effective treatment or even a cure. For example, assume someone discovered that the CFTR protein does not deteriorate and does not need continuous replacement by the cells once they are in adequate quantities. Then a good potential treatment might be to transfer the CFTR proteins from an unaffected individual to the CF patient. However, such treatments increase the number of affected individuals. Since CF is inherited, two homozygote recessive individuals can live long enough to reproduce and have children also affected by CF (Hartwell, 2008). This means that the treatment needs to be cost-effective and able to help an increasing population of CF patients.
In conclusion, CF is caused by an ion transport deficiency which prevents the epithelial cells from hydrating the lungs from the outside (Karp, 2010). This causes thick mucus to develop in the lungs and eventually causes early death (Karp, 2010). CF is a genetic disorder and there are many different mutations that causes CF to develop differently (Hartwell, 2008). Researchers have found some treatments, but no cure has been found.
Freeman, S (Ed.). (2008). Biological Science. San Francisco, CA: Pearson Education, Inc.
Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, Veres RC (Ed.). (2008). Genetics: From Genes to Genomes. New York, NY: McGraw-Hill Companies, Inc.
Karp G. (Ed.). (2010). Cell and Molecular Biology: Concepts and Experiments. Danvers, MA: John Wiley and Sons, Inc.
I relied heavily on textbooks for this essay, since they give detailed information compiled from the findings of other researches, not recent discoveries as I would see in journal articles. I approached this problem from the molecular (including genetics) and cellular approach and I learned some information from it about CF. As little as a single amino acid deletion could cause very adverse effects and prevents organelles from working on it. Also, the biological system is interconnected that the failure of a protein from functioning hinders the function of other cellular activities.