Cystic Fibrosis Flashcards
How many people carry the CF gene?What type of gene condition is it?
1 in 25Autosomal recessive
What is the cystic fibrosis trans-membrane conductance regulator gene?
The CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. This protein is activated by ATP and functions as a chloride channel (pumps chloride out of the cell) across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes.
What happens at a biological level if the CFTR gene is faulty?
Due to the fault with CFTR, chloride can’t be pumped out effectively and there is also a negative effect on its coupled channel, the Epithelial Na+ channel (ENAC), causing an increase in Na+ movement into the cellWater follows sodium causing secretions to be dried outit also stops sodium being pumped in
What are the consequences in a fault with CFTR? (8)
Salty sweatIntestinal blockagefibrotic pancreasfailure to thriverecurrent bacterial lung infectionscongenital bilateral absence of vas deferensfilled sinusesgallbladder anad liver disease
How does a mutation in the CFTR DNA cause cystic fibrosis?
CFTR DNA mutation = abnormal CFTR protein = ion transport abnormalities = abnormal secretions = blocked ducts and impaired mucosal defence = infection and inflammation = cystic fibrosis
How many classes of defects in CFTR are there?
5
Class I defect in CFTR?
No CFTR synthesis
Class II defect in CFTR?
CFTR trafficking defect (most common type)
Class III defect in CFTR?
The CFTR protein makes it to the cell membrane but does not open properly due to binding of ATP meaning chlorine cannot be conducted through it
Class IV defect in CFTR?
CFTR protein reaches the membrane and does partly work but channel is narrowed and therefore does work effectively
Class V defect in CFTR?
Reduced CFTR transcription and synthesis meaning some proteins are made and work effectively but not enough of them are made
Are all mutations equal?
No
What are the basic steps to forming a protein? (5)
DNA is transcribed and splicedmRNA is translated and modified before being transported
What is a point mutation?
a mutation affecting only one or very few nucleotides in a gene sequence.
What is a missense mutation?
a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid.
What is a frameshift mutation?
Deletion or insertion of a number of bases that is not a multiple of 3.
What mutation do 1 in 25 people have that makes them a carrier of CF and causes 70% of CF cases (Class II)?What does this do?
F508DelCauses a deletion of the three nucleotides that comprise the codon for phenylalanine (F) at position 508 on chromosome 7.
What is the mutation that leads to 4-6% of CF cases (class III)?What does this cause?Other name for this gene
G551DA “missense” mutation: instead of a glycine amino acid (G), aspartate (D) is added(*for a recessive disease you can have different mutations in each copy of the gene)”Celtic gene”
