Question

Cystic fibrosis is genetic disease caused by mutations in the CFTR gene. The consequence of this is production of an abnormal transmembrane protein that is responsible for producing sweat, mucus, and digestive fluids.

Explain in depth the correlation between the defective gene and the abnormal protein that is produced. Be sure to mention the process involved in protein production, whether or not those process(s) have occurred, and their end products. Provide details in your explanation and support your answer with facts from your textbook, research, and articles from scholarly journals.

Answer 1

Cystic fibrosis :

Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.

Protein production :

CF is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein.Those with a single working copy are carriers and otherwise mostly healthy.CFTR is involved in the production of sweat, digestive fluids, and mucus.When the CFTR is not functional, secretions which are usually thin instead become thick.The condition is diagnosed by a sweat test and genetic testing.Screening of infants at birth takes place in some areas of the world.

Several mutations in the CFTR gene can occur, and different mutations cause different defects in the CFTR protein, sometimes causing a milder or more severe disease. These protein defects are also targets for drugs which can sometimes restore their function. ΔF508-CFTR, which occurs in >90% of patients in the U.S., creates a protein that does not fold normally and is not appropriately transported to the cell membrane, resulting in its degradation.

Other mutations result in proteins that are too short (truncated) because production is ended prematurely. Other mutations produce proteins that do not use energy (in the form of ATP) normally, do not allow chloride, iodide, and thiocyanate to cross the membrane appropriately,^[50] and degrade at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.

The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and all other remaining exocrine glands in the body. The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. This channel is primarily responsible for controlling the movement of halide anions from inside to outside of the cell; however, in the sweat ducts, it facilitates the movement of chloride from the sweat duct into the cytoplasm. When the CFTR protein does not resorb ions in sweat ducts, chloride and thiocyanatereleased from sweat glands are trapped inside the ducts and pumped to the skin.

Additionally hypothiocyanite, OSCN, cannot be produced by the immune defense system. Because chloride is negatively charged, this modifies the electrical potential inside and outside the cell that normally causes cations to cross into the cell. Sodium is the most common cation in the extracellular space. The excess chloride within sweat ducts prevents sodium resorption by epithelial sodium channels and the combination of sodium and chloride creates the salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test.