How Are Genetics Related to Cystic Fibrosis?

The development of cystic fibrosis is caused by genetics. The disease occurs when there is a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is the gene responsible for the movements of negatively charged particles known as chloride ions into and out of cells. 

 The component chloride comes from sodium chloride, which is a common salt present in sweat. The component holds important roles in the cells, including controlling the flow of chloride ions that control the water movement in tissues, a function that results in the production of thin, freely flowing mucus.There are more than 180 known mutations in the CFTR gene that causes cystic fibrosis and disrupt the normal work of the chloride channels. 

Due to the defect, the chloride is unable to properly regulate the flow of chloride ions and water through the cells. Therefore, the cells near the lungs, pancreas, and other organs end up producing thick and sticky mucus instead of the normal watery and slippery substance. Genetics and environmental factors also impact the severity of the disease.

The very existence of 180 known mutations and numerous other unknowns make it difficult to find a cure or define an effective treatment for the disease.Mutations in the CFTR gene cause cystic fibrosis. The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. Chloride is a component of sodium chloride, a common salt found in sweat. 

Mode of inheritance and risk of passing on the CF gene

CF has a simple Mendelian autosomal recessive inheritance (figure 2). This means that people with CF have two copies of the mutant CFTR gene, one inherited from each parent. Carriers have one normal and one mutant CFTR gene and their health is not affected because the normal CFTR gene ensures production of enough protein to allow normal cellular function. 

Carriers have a 50% chance of passing their mutant CFTR gene onto their children. When both parents are carriers there is a 25% chance in every pregnancy that the child will have CF, a 25% chance that the child will have two normal CFTR genes and a 50% chance that the child will be a carrier (figure 2).

Figure 2: Simple Mendelian autosomal recessive inheritance. Affected individuals will have two copies of the mutant CFTR gene, one inherited from each parent. 

 The Gene Is Found  

As these studies of chloride transport were progressing, many scientists were engaged in an intense race to find the gene responsible for cystic fibrosis. That effort culminated in 1989, when a large group of collaborators, led by Lap-Chee Tsui and John R. Riordan of the Hospital for Sick Children in Toronto and by Francis S. Collins, then at the University of Michigan and now the Director of the Human Genome Project at NIH, announced it had isolated the gene.

 Aware that the protein product of the gene probably influenced the movement of chloride directly or indirectly, they named the protein the cystic fibrosis transmembrane conductance regulator (CFTR). While searching for the gene, the team also identified an abnormality in the DNA that appeared to account for about 70 percent of cystic fibrosis cases. That aberration, often denoted as the AF508 mutation consists of the deletion of three nucleotides ( DNA building blocks) from the gene. That loss causes the protein product of the gene to lack a single amino acid: phenylalanine at position 508.