Introduction to Disease and Symptoms.
Cystic Fibrosis is the most commonly deadly genetic disease for children in America. It is caused by over a thousand different mutations to the gene that creates the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), a transmembrane chlorine channel. The chlorine channel is vital in almost all secretory activities in the body, including: sweating, mucus secretion in the lungs, intestinal secretions and gall bladder secretion. The most commonly referred to symptom is progressive lung disease; it is caused by the secretion of mucus in the lungs that is too thick to be moved by the bronchial cilia. This mucus then acts as a breeding-grounds for harmful bacteria which eventually lead to lung death if it is not treated. Other symptoms include male infertility, increased salt content in sweat and digestive problems.
CF is found in most abundance in Caucasians, at a frequency of 1/2,500 newborns. This is much higher than in any other ethnic group. (Andersson) .
Genetic Basis.
The mutations that cause CF are on Chomosome 7, near the middle of the Q arm. The most common mutation that causes CFTR is a deletion that causes a frame-shift mutation. The deleted three nucleotides (all thymine) produce a phenylalanine amino acid in the normal CFTR protein. In the mutant form the phenylalanine is missing. Nearly 70% of CF patients have this mutation, named deltaF508. It is an autosomal recessive disorder, meaning the child must receive a mutant copy from heterozygous parents. http://genome.gsc.riken.go.jp/hgmis/posters/chromosome/cftr.html.
Cellular Basis.
CFTR is the channel responsible for the symptoms seen in cystic fibrosis. It is an ABC transporter with two membrane spanning domains (MSDs) two nucleotide binding domains (NBDs) and a Regulatory domain (R). The channel allows Cl- to diffuse freely across the membrane (in normal CFTR) as the concentration gradients change.