What class of mutation is delta F508?
That is, ΔF508 is a class 2 mutation in the sweat gland but a class 3 mutation in the airway and gut, so a therapy effective in one tissue might not apply to another. Disease of the airway is the major cause of mortality in CF, so understanding the effect of ΔF508 on the respiratory epithelium is of major importance.
What category does the CFTR protein belong to?
The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body.
How are CFTR mutations classified?
There are five classes of CFTR mutations: protein production, protein processing, gating, conduction, and insufficient protein.
Is F508 a gene?
F508del (formerly ΔF508) accounts for 70% of the mutant CFTR genes worldwide. It corresponds to the deletion of phenylalanine (F) at position 508 of the CFTR protein. There are, however, over 1500 other CFTR gene mutations reported at the time of writing this article, although most of them are rare.
What chromosome is CFTR gene on?
Although there have been numerous reports from around the world of mutations in the gene of chromosome 7 known as CFTR (cystic fibrosis transmembrane conductance regulator), little attention has been given to integrating these mutant alleles into a global understanding of the population molecular genetics associated …
Which type of gene mutation produced the cystic fibrosis allele?
CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. A three-nucleotide deletion (delta F508) causing the loss of a phenylalanine residue in the tenth exon of the CFTR gene has been found on 70% of CF chromosomes.
How does delta F508 cause cystic fibrosis?
The most common mutation in the gene associated with cystic fibrosis (CF) causes deletion of phenylalanine at residue 508 (delta F508) of the gene product called CFTR. This mutation results in the synthesis of a variant CFTR protein that is defective in its ability to traffic to the plasma membrane.
How many CFTR gene mutations are known?
More than 1,700 mutations of the CFTR gene have been identified. Although some are common, others are rare and found in only a few people.
How many CFTR genes are there?
All people have two copies of the CFTR gene, and there must be mutations in both copies to cause CF. More than 1,700 mutations of the CFTR gene have been identified. Although some are common, others are rare and found in only a few people.
How is ΔF508 CFTR function assayed?
ΔF508 CFTR function is assayed in a plate reader by quantifying YFP fluorescence quenching in response to iodide addition, (b)Corrector assays. YFP-based assay: cells are incubated with test compounds at 37 °C for 24 h ΔF508 CFTR function is assayed by iodide addition in the presence of forskolin and the potentiator genistein.
Is DeltaF508 the most common CFTR mutation?
Background and aims: Deletion of the codon for phenylalanine at position 508 (DeltaF508) is the most frequent disease-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
What is wrong with ΔF508 CFTR transfected cell lines?
A concern in corrector discovery is the use of ΔF508 CFTR transfected, overexpressing cell lines, in which compounds with potentially high efficacy in native human CF cells may escape detection.
Is single drug therapy for cystic fibrosis caused by ΔF508 mutation possible?
Whether single drug therapy for CF caused by the ΔF508 mutation is possible or not remains to be determined. The alternative, as suggested by the data and analyses described in this review, is multi-drug therapy using more than one corrector or potentiator as PC, perhaps in combination with a PR.