lecture 7 Flashcards
what is cystic fibrosis?
inherited condition causing sticky mucus to build up in lungs and digestive system
how is cystic fibrosis caused?
-mutation in the CFTR (cystic fibrosis transmembrane regulator) gene
what is the CFTR gene?
-channel protein that transports chloride ions out of the cells and into the mucus, so water can move into the mucus by osmosis, which makes the mucus watery.
how is CF characterised?
severe lung and pancreatic disease
what type of inherited condition is CF?
autosomal recessive - need 2 alleles to be be defective
what is the most common mutation in CFTR gene?
F508 del -> loss of phenylalanine at position 508 in nuclear binding domain 1 (NBD1)
what classes are minimal or function mutations?
class l, ll and lll -produces most severe phenotype
which classes are residual function mutations?
class lV, V and Vl
what does class l mutation cause?
-no protein in CFTR channel
-encoded by G542X
what does class ll mutation cause?
-no traffic
-no processing
-protein made in ER but isn’t transported to Golgi network
-encoded by F508del
what does class lll mutation cause?
-no function
-doesn’t respond to signals to switch on/off
-encoded by G551D
what does class lV mutation cause?
-less function
-normal number of channels, just less active
-encoded by R117H
what does class V mutation cause?
-less protein
-mRNA isn’t translated as efficiently
-some function but less than usual
-encoded by A455E
what does class VI mutation cause?
-less stability
-protein doesnt reside in apical membrane for as long
-shorter half life
-encoded by rF508del
where is CFTR located in the airway?
-ciliated, secretory (club) and ionocyte airways
and serous cells of submucosal glands
