Student seminars 9/16- cystic fibrosis

Question 1

cystic fibrosis is multi-systemic meaning…

Answer 1

relating to, involving, or affecting more than one bodily system.
- Respiratory system
- Digestive system
- Reproductive system
- Etc.

Question 2

NIPT and CF

Answer 2

• There are limits to NIPT for Cystic Fibrosis. Every genetic mutation that causes CF have not been discovered, meaning a person can still be a affected by CF even if no mutations have been identified through NIPT.
  
  • Only general mutations are tested for.
  • Could leave to inappropriate interpretations of results

Question 3

inheritance pattern

Answer 3

autosomal recessive

Question 4

cause of CF

Answer 4

A mutation in the Cystic Fibrosis Transmembrane Conductance Regulatory (CFTR) protein

Question 5

mutation type

Answer 5

single nucleotide substitutions or small deletions

Question 6

5 classes

Answer 6

Protein Production Mutations
(Class 1)
Protein Processing Mutations
(Class 2)
Gating Mutations (Class 3)
Conduction Mutations (Class 4)
Insufficient Protein Mutations (Class 5)

Question 7

Protein Production Mutation (Class 1)

Answer 7

include nonsense or splice mutation that interferes with the production of the CFTR protein

Question 8

Protein Processing Mutation (Class 2)
**most common

Answer 8

Cannot form the right shape for CFTR, therefore cannot function properly (Structure/Function)

Question 9

Gating Mutations (Class 3)

Answer 9

Lock the gate in a closed position so Chloride cannot get through.

Question 10

Conduction Mutations (Class 4)

Answer 10

Change the inside shape of the tunnel making it harder for Chloride to smoothly pass through

Question 11

Insufficient Protein Mutations (Class 5)

Answer 11

Reduced number of CFTR proteins on cell surfaces.

Question 12

ATP-gated anion channel crosses…

Answer 12

Cl- across the epithelial cell membrane

can do other anions

Question 13

where is epithelial located

Answer 13

Line the inside and outside of the body
- These include: The lungs, pancreas, sweat glands, intestines, and reproductive tract

Question 14

Cl transport significance

Answer 14

Maintenance of fluid balance on the epithelial surface

Question 15

Intra-membranous Domain (IMD)

Answer 15

Form the channel pore of the CFTR protein
- IMDs are linked and influenced by the NBDs

Question 16

Nucleotide Binding Domain (NBD)

Answer 16

Regulates the opening and closing of the channel

Question 17

Regulatory Domain

Answer 17

• Determines channel activity through phosphorylation
• Located immediately after the N-terminal of NBD

Question 18

CFTR in its inactive state will be

Answer 18

closed

Question 19

closing CFTR involves

Answer 19

a membrane bound phosphatase (enzyme) will remove the phosphate group from the R domain (channel will remain open)  It is not until the hydrolysis of the second ATP molecule (Pi + ADP) that the channel will close.

Question 20

opening CFTR

Answer 20

cAMP activates PKA - PKA will go on to phosphorylate the regulatory domain
-ATP binds to NBD1 causing a conformational change bringing IMDs closer also forming a WEAK NDB1-NBD2 heterodimer (1 ATP molecule linking the two NBDs) - Once the second ATP binds
-turns WEAK NBD1-NBD2 heterodimer into a STRONG NBD1-NBD2 heterodimer -
- Once there is phosphorylation of the R domain and two ATP molecules bound to the dimer
-the channel will open.

Question 21

Importance of the Mucus Membrane

Answer 21

lower respiratory tract
-The mucus membrane is important because it traps foreign molecules so that cilia (small, hair-like projections) can sweep the mucus with these FM trapped up and out of our airway

Question 22

mucus secreted by

Answer 22

goblet cells

Question 23

working mucus membrane…

Answer 23

clears foreign material and prevents lung infections

Question 24

F508del impacts

Answer 24

• CFTR protein cannot get chloride across membrane efficiently leading to an unmaintained liquid layer where cilia are unable to move

Question 25

F508del

Answer 25

deletion of phenylalanine at amino acid 508 (class 2)