CYSTIC FIBROSIS
(CF)
Symptoms
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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
Tests
Foetal proteins tested by amniocentesis
 Sodium ion concentrations in sweat
 Carriers tested using DNA probes for
mutant allele
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© 2008 Paul Billiet ODWS
Treatment
Physiotherapy helps reduce lung
congestion
 Pancreatic extracts can help digestive
problems
 Gene therapy being developed
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© 2008 Paul Billiet ODWS
Frequency
1 in 2500 births in N Europe
 1 person in 25 is heterozygous (carrier)
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© 2008 Paul Billiet ODWS
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
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© 2008 Paul Billiet ODWS
Some CFTR mutations
Name
Nucleotide Change
Exon
Consequence
-816C->T
C to T at-816
5'
flanking
promoter mutation?
-471delAGG
deletion of AGG
from-471
5'
flanking
promoter mutation?
M1V
A to G at133
1
no translation initiation
M1I
G to T at135
1
Met to Ile at codon 1
S4X
C to A at143
1
Ser to Stop at codon 4
174delA
deletion of A
between 172-174
1
frameshift
175insT
insertion of T after
175
1
frameshift
185+1G->T
G to T at 185+1
intron 1
mRNA splicing defect
© 2008 Paul Billiet ODWS
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
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© 2008 Paul Billiet ODWS