CYSTIC FIBROSIS (CF)

1. CYSTIC FIBROSIS (CF)

2. Symptoms • Incorrect folding of the the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein results in its destruction • The cell membranes in epithelial cells of lungs, pancreas, colon and urinogenital tract lack chloride ion pores • Chloride and sodium imbalance results • Excessively salty sweat • Mucus secretion becomes thick and viscous. It cannot easily be cleared • Chronic lung congestion • Pancreatic obstruction • Liver damage and diabetes common amongst patients. • Median survival 19 years. © 2008 Paul Billiet ODWS

3. Tests • Foetal proteins tested by amniocentesis • Sodium ion concentrations in sweat • Carriers tested using DNA probes for mutant allele © 2008 Paul Billiet ODWS

4. Treatment • Physiotherapy helps reduce lung congestion • Pancreatic extracts can help digestive problems • Gene therapy being developed © 2008 Paul Billiet ODWS

5. Frequency • 1 in 2500 births in N Europe • 1 person in 25 is heterozygous (carrier) © 2008 Paul Billiet ODWS

6. Cause • A single mutant recessive allele of the CFTR gene • 90% Caused by a deletion on the codon of position 508 (amino acid phenylalanine) • About 400 mutations of this gene are known • The CFTR gene is located on chromosome 7 © 2008 Paul Billiet ODWS

7. Some CFTR mutations © 2008 Paul Billiet ODWS

8. Evolution • The high frequency of heterozygotes in N. Europe suggests a selective advantage • Some geneticists suggest it can protect against diseases like • BUT salt loss in sweat by CF carriers did not give them the advantage in hot climates • So CF frequency increased in temperate climates not in the tropics © 2008 Paul Billiet ODWS