Cystic Fibrosis as a Genetic Disorder - Essay Example

Cystic Fibrosis Cystic fibrosis is a recessive genetic disorder caused by a single mutated gene; the mutated gene is cystic fibrosis transmembrane regulator (CFTR). It occurs when both parents to a patient are carriers of the defective CFTR gene thereby contributing to the embryo. The carrier of a single mutated gene is asymptomatic and cystic fibrosis is passed by co-inheritance of two mutated CFTR genes, single gene from each parent. It is a deadly disease affecting an approximate 30,000 people living in the United States and about 70,000 around the world. Caucasians are the highly affected by cystic fibrosis patients, although it occurs in all races (Giddings 7). The CFTR protein is located in epithelial cells, which form a lining of major body organs. The CFTR protein in people without cystic Fibrosis controls the flow of salt and water through the epithelial walls. As a result, it retains mucus secreted thin and watery. The thin mucus is important since it protects the lining of the liver, lungs, pancreatic glands, reproductive organs and digestive organs. A Cystic Fibrosis patient who has a mutated CFTR gene, the passage of sodium chloride through the epithelial cells does not occur normally. The body lacks a healthy CFTR protein needed to maintain a balance of salt and water leading to a lot of salt in sweat and making the mucus produced by the mucous gland too thick and sticky. The thick mucus clogs and obstructs body organs, linings and passageways thus preventing the normal functioning of body organs (Bjorklund 15-16). Cystic fibrosis causes acute respiratory problems; this is due to acute haemoptysis and pneumonia. The infecting organisms of patients who have pneumonia include Staphylococcus aureus and Pseudomonas aeruginosa. The body has a small amount of functional CFTR to bind with the infectious bacteria resulting in obstruction of the airways. As the obstruction increases, it becomes very hard for air to pass through during inhalation and exhalation. This leads to expansion of the alveoli leading to trapping of air in small tubes. Over time, this causes barrel-shaped chest leading to increased pulmonary artery pressure that in turn causes heart failure. In addition, thick and sticky mucus, which is the main symptom in cystic fibrosis patients, clogs the bronchioles and as a result, parts of the lungs become blocked off. The small air passage also becomes weak and loses the ability to work properly; this often develops to bronchiecstasis. The patient coughs a lot and wheezes while breathing. In addition, cystic fibrosis patients get infections of the lungs due to fungus Aspergillus fumigatus which causes very thick secretions which are resistant to antibiotics. The infections are very deadly if not well treated (Grossman and Lisa 47-48). Cystic fibrosis patients experience problems in the gastrointestinal tract, which are majorly due to inability of the pancreas to function properly to supply digestive enzymes to the digestive organs. The loss of CFTR function leads to changed viscosity of the pancreas and eventual destruction of the organ. The volume of pancreatic enzymes produced by the pancreas decrease therefore it secretes thick mucus that clogs the pancreatic ducts leading to lower pancreatic enzymes being secreted. This causes poor digestion and absorption of proteins into the body, in order to correct this; the Cystic fibrosis patients use pancreatic enzymes supplements, which mostly impair absorption of iron. The distal part of the intestine is filled with faecal matter that manifests in constant vomiting, anorexia and a decrease in one’s bowel movement. Distal intestinal obstruction syndrome (DIOS) results due to faulty secretion of sodium chloride and water from the epithelium of the intestines; leading to acute dehydration. The patients pass a lot of undigested food out of the body leading to the body becoming weak. The poor nutrition leads to the body developing slowly and its reduced ability to handle infections (Grossman and Lisa 48). Most cystic fibrosis patients are reported to suffer from liver cirrhosis. The main age of prevalence is 7-9 years and increases with increase in one’s age. The liver cirrhosis is majorly associated with the failure of the pancreas to work properly. Patients with liver disease thus have mutations linked to the loss of CFTR function in addition to pancreatic insufficiency. In addition, cystic fibrosis affects the patient’s endocrine system. A large percentage of the patients have Cystic fibrosis -related diabetes that is majorly diagnosed after the age of thirty years. The condition causes insulin deficiency caused by the obstruction of the pancreas. The patients require high-energy meals unlike the diabetes mellitus patients. The high glucose metabolism is caused by severe dehydration, poor absorption of nutrients, numerous infections and slowed gastrointestinal transport time (Cutting 249). Cystic fibrosis causes the sweat glands to work improperly. Due to the decreased levels of CFTR protein, which regulates sodium chloride in sweat, cystic fibrosis patients experience excessive loss of sodium chloride due to intense heat or following intense exercise. Due to minimal sodium chloride level in the body, the patients experience tiredness, fever, stomach pain, dehydration, weakness and reduced appetite. Moreover, cystic fibrosis among men causes the malformation of vas deferens and even some lacking it, this causes sterility in most men. On the other hand, women tend to remain fertile but take more time to conceive as compared to women who lack Cystic fibrosis. The thick mucus produced plug the oviduct and clog the cervix; decreasing sperm movement therefore reducing the chances of conception (Grossman and Lisa 49). Identification of new genes and their mutations improve the understanding of single gene disorder and complex disease processes associated with the genes. There are numerous molecular methods, which are used to detect cystic fibrosis mutations, which include Restriction fragment length polymorphism (RFLP). This method uses restrictive enzymes in the study of genes. The restrictive enzymes recognize and cleave DNA at a specific sequence in order to produce a small group of fragments. Mutation of a gene results in the elimination or creation of a restriction enzyme at a recognition-cut point. This method uses polymerase chain reaction (PCR) amplification of the focus fragment hence often referred to as RFLP-PCR. The point mutation is recognised easily after multiplication of the DNA, which entails mutation and incubation together with the restriction enzyme. The incubation products are then separated using a dye and are developed with UV radiation. The size and number of the fragments are clearly changed by mutation and the change can be studied (Konstantinos et al 156). Moreover, Allele specific oligonucleotide probes (ASO) is a molecular method used in detection of the CFTR gene mutation. Bead array technology is majorly used in this method. The method uses small portions of synthetic DNA molecules consisting 20 nucleotides and composed in order to detect recognition-point mutations. The nucleotides undergo hybridization with complementary sequences and the position of the modification is centre of the molecule. Usually each investigation entails two probes synthesized per mutation. The first complements the normal sequence while the second one complements the mutated. Finally, the PCR result is hybridized with the probes in a nylon membrane used for hybridization. Single-Strand Conformation Polymorphism (SSCP) is another method used to detect gene mutation. This method uses PCR amplification to denature the PCR product with heat and then electrophoresis on a non-denaturing gel. During electrophoresis the single strand DNA fragment form a three-dimensional shape, which depends on the initial sequence? Eletrophoretic mobility of separation influences the shape of the single strand fold formed. The difference in the sequence between the normal and the mutated DNA is then studied and extend of mutation determined. This method is based on the observation that single stranded DNA falls into a unique fold determined by its primary sequence. As a result, any alteration results in conformational change that can then be detected by the eletrophoretic mobility (Konstantinos et al 156). Works cited Bjorklund, Ruth. Cystic Fibrosis. New York: Marshall Cavendish Benchmark, 2009. Print. Cutting, Garry R. "MODIFIER GENETICS: Cystic Fibrosis." Annual Review Of Genomics & Human Genetics 6.1 (2005): 237-C-1. Giddings, Sharon. Cystic Fibrosis. New York: Chelsea House, 2009. Print. Grossman, Sheila, and Lisa C. Grossman. "Pathophysiology Of Cystic Fibrosis Implications For Critical Care Nurses." Critical Care Nurse 25.4 (2005): 46-51. Konstantinos, Kakavas V. , Antonios, Vlachos T. , Agelos, Papaioannou and Argiri, Noulas V. “PCR–SSCP: A Method for the Molecular Analysis of Genetic Diseases.” Mol Biotechnol (2008) 38:155–163. Read More