Cystic Fibrosis (CF) is a genetic disorder that affects the body’s secretory glands, which produce mucus and sweat. It is one of the most common inherited diseases, particularly among populations of Northern European descent. CF leads to the production of abnormally thick, sticky mucus that causes problems in the respiratory, digestive, and reproductive systems. This buildup obstructs airways in the lungs, leading to chronic infections and progressive lung damage. The thick mucus also blocks ducts in the pancreas, preventing digestive enzymes from reaching the small intestine.
Identifying the CF Gene Location
The gene responsible for Cystic Fibrosis is found on Chromosome 7, one of the 23 pairs of chromosomes present in human cells. The specific gene located on the long arm of this chromosome is called the Cystic Fibrosis Transmembrane Conductance Regulator, or CFTR gene. This discovery was a scientific achievement in 1989, providing the first clear molecular understanding of the disease. The identification of the CFTR gene’s precise location allowed researchers to begin investigating the function of the protein it encodes and how its malfunction causes CF.
The Role of the CFTR Protein
The CFTR gene contains the instructions for manufacturing a protein called the CF Transmembrane Conductance Regulator. This protein functions as a channel embedded in the cell membranes of epithelial cells throughout the body, including those lining the lungs, pancreas, and sweat glands. The normal function of the CFTR protein is to regulate the passage of negatively charged particles, specifically chloride and bicarbonate ions, across the cell membrane. This ion transport maintains the necessary hydration and fluidity of external secretions, such as mucus.
When the CFTR channel works correctly, it allows chloride ions to move out of the cell, drawing water along with them through osmosis to thin and hydrate the mucus coating. The resulting secretions are thin and slippery, enabling them to easily lubricate and be cleared from the airways. When mutations occur in the CFTR gene, the resulting protein is either not produced, produced in insufficient quantities, or is structurally defective. This disruption to the flow of chloride ions impairs the movement of water across the cell membrane.
Without the proper movement of water, the mucus and other secretions become dehydrated, thick, and sticky, leading to the characteristic obstruction seen in CF. The most frequently encountered mutation is known as Delta F508, which involves the deletion of a single amino acid, phenylalanine, at position 508. This defect results in a misfolded protein that is destroyed by the cell before it can reach the cell surface to perform its function. The Delta F508 mutation is present in at least one copy of the gene in approximately 90% of individuals with CF.
Understanding CF Inheritance Patterns
Cystic Fibrosis follows an inheritance pattern known as autosomal recessive. This means a person must inherit two copies of the mutated CFTR gene, one from each parent, to develop the condition. Since the gene is on Chromosome 7 (a non-sex chromosome), it affects both males and females equally.
Individuals who inherit only one mutated copy and one normal copy are known as carriers. A carrier typically does not exhibit CF symptoms because the single normal gene copy is sufficient to produce functional CFTR protein. Carriers can pass the mutated gene on to their children.
When both parents are carriers, there is a specific probability for each pregnancy. There is a 25% chance the child will inherit two mutated genes and have CF. There is a 50% chance the child will inherit one normal and one mutated gene, making them a carrier. Finally, there is a 25% chance the child will inherit two normal copies and be neither affected nor a carrier.