Flashcards in CF - L2 Deck (14)
What is the pattern of inheritance of CFTR and the incidence? and carrier frequency
1 in 250,000
1 in 25
What does being a carrier have a selective advantage for? (possibly)
cholera (you die from dehydration)
typhus (bacteria uses CFTR to enter cell)
What are typical pedigree traits?
de novo mutations rare
What phenotype are classes I, II & III usually associated with?
severe lung disease and PI
What phenotype are classes IV & V usually associated with?
PS and milder lung disease
What is the difference in penetrance of F508del and R117H?
F508del, usually severe PI
What does the penetrance of R117H depend on?
intragenic polymorphism in intron 8 on same allele in cis
R117H & 5T: likely to have disease symptoms
R117H & 7T: unlikely to have disease symptoms
R117H & 9T: highly unlikely for symptoms
How do you identify genetic modifiers of CF?
candidate gene association
What are some genetic modifiers of lung disease?
EDNRA: probable effect, smooth muscle tone
MBL2: probable effect, innate immunity
TGFB1: probable effect, regulating inflammation and tissue remodelling
What are some genetic modifiers of intestinal obstruction?
MSRA: methionine sulphide reductase modifies intestinal enzymes
What are some genetic modifiers of diabetes?
TCF7L2: proliferation and function of beta cells
What are some environmental modifiers?
What types of screening are there for CF?