Cystic fibrosis: a transport problem?

Article Abstract:

The gene that is defective in cystic fibrosis has been identified; specific changes in this gene can be correlated with the presence of the disease. Many of the symptoms of cystic fibrosis stem from abnormally thick secretions, especially in the lungs. These symptoms are related to a problem in the transport of chloride ions (electrically charged particles) across membranes. Thus, it was thought that the defective gene in cystic fibrosis might encode a protein that works as a channel that ions pass through. The identified gene contains a sequence of deoxyribose nucleic acid (DNA) similar to a group of proteins involved in the transport of molecules. This conserved sequence also binds and breaks down nucleoside triphosphates, such as ATP (adenosine triphosphate), which is involved in the production of energy. The mutations found in the defective gene are present in the region of the molecule that is similar to transport proteins. A model of the protein involved in cystic fibrosis has been presented based on its similarities to other molecules whose structure is known. However, there are differences between the protein involved in cystic fibrosis and similar proteins, which may make this model incorrect. Further experiments will test this model. However, other scientists do not feel that the protein is an channel for chloride molecules. Channels do not require the degradation of ATP. Chloride channels allow the flow of chloride ions in both directions, while the proteins similar to the gene involved in cystic fibrosis only allow the flow of ions in one direction. Other evidence that this gene does not code for a chloride channel includes: the size of the molecule is too large; chloride channels differ in different tissues, but there is only one defective gene in cystic fibrosis; and other characteristic sequences of chloride channels are not present. Therefore, it is thought that the protein is a transporter, not a chloride channel, and that the protein may transport a molecule that regulates a chloride channel. (Consumer Summary produced by Reliance Medical Information, Inc.)

Causes of

---

A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein

Article Abstract:

The defective gene in cystic fibrosis (CF) has been identified. It encodes a protein known as the CF transmembrane conductance regulator (CFTR). The functional regions of the protein include two sites for the binding of adenosine triphosphate (ATP) (which is involved in the production of energy); a regulatory region; and two regions that can interact with the cell membrane. A mutation that occurs in approximately 70 percent of CF cases is present in one of the regions that binds ATP. Regions of the defective gene were sequenced in 38 patients with CF. Four additional types of mutations were found clustered in a small region of one of the nucleotide binding regions in the patients, indicating that this region is important for the protein to function properly. The gene that is defective in CF contains sequences that are similar to a group of proteins involved in the transport of molecules, including genes that encode proteins cause resistance to many types of drugs by exporting the drugs out of the cells, and other transport proteins that also bind ATP. The region of the gene that contains the newly identified mutations are similar in these other proteins of the family. This conservation is further evidence that the region is functionally important and that the CFTR protein is a member of the transporter gene family. The study further identifies possible defects in the gene which cause cystic fibrosis. Knowledge of these defects allow a better understanding of the function, which may lead to potential methods of treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

---

Screening for genetic mutations

Article Abstract:

Peptide nucleic acid (PNA) is an effective DNA mimic, and may provide a good and efficient DNA probe for screening genetic mutations in humans. PNA appears to be capable of detecting single base substitutions. In PNA, the DNA ribose-phosphate backbone is replaced by the pseudo-peptide N-(2-aminoethyl)glycine. Hybridization occurs rapidly by Watson-Crick pairing. The hybrid complex products have a different ratio of electrical and frictional forces from that of DNA due to the non-ionic nature of PNA. The complexes are easily separable by free-solution electrophoresis. The PNA probe procedure is discussed.

Methods, Innovations, DNA probes, Genetic screening, Genetic testing

Similar abstracts:

• Abstracts: Expression and characterization of the cystic fibrosis transmembrane conductance regulator. Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells
• Abstracts: Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein
• Abstracts: Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain
• Abstracts: Hereditary spherocytosis associated with a deletion of human erythrocyte ankyrin gene on chromosome 8. Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2
• Abstracts: Additional deletion in sex-determining region of human Y chromosome resolves paradox of X,t(Y;22) female. What makes a man a man?

This website is not affiliated with document authors or copyright owners. This page is provided for informational purposes only. Unintentional errors are possible.