Lecture 9 Flashcards
The carrier frequency (northern euro) is
1 in 25
incidence of CF is..
1 in 2500-3000 live births
people of Japanese ethnicity are at a ___ risk of CF
low
There is some but variable correlation between class of mutation and phenotype, especially with ______ function
pancreatic function
Classes __,__ and ___ (and probably __) usually have more severe lung disease and PI
Classes I, II and III (and probably VI)
Classes IV and V usually associated with __and milder ___disease
Classes IV and V usually associated with PS and milder lung disease
The clinical penetrance of R117H depends on another intragenic polymorphism. Examples are things like
male infertility (with borderline or elevated sweat chloride)
Twin studies can be used to look at concordance in MZs and DZs for clinical features - to estimate _____ _____
genetic control
What are the reasons to identify genetic modifiers?
Identifies new targets for therapies
Increases understanding of disease variability
Expect these genes/variants to be minimally penetrant in healthy poeple but effects unmasked in CF patients
Theses gene modifiers, therefore, may contribute to development of progression of common disease in general population (e.g type II diabetes)
How do you identify a genetic modifiers?
Association studies:
Linkage - track genes associated with specific phenotypes in families with CF
Candidate gene association - correlating genes with known function
Genome wide association studies - examine DNA markers at many positions on multiple chromosomes
What are the limitations of Gonome wide association studies?
When genes are less penetrant, they need greater sample size
need to replicate studies for validation
need to demonstrate correlation
EDNRA encodes _____ receptor type _
Variants of this alter ____ ______ ____ in airways and/or vasculature and therefore may modify CF lung disease
EDNRA encodes endothelin receptor type A
Variants of this alter smooth muscle tone in airways and/or vasculature and therefore may modify CF lung disease
_____ encodes mannose binding lectin
It has a role in ______ _______
A deficiency in this will predispose to early ________ with bacteria and therefore leads to more severe lung disease
MBL2 encodes mannose binding lectin
It has a role in innate immunity
a deficiency in this will predispose to early infection with bacteria and therefore leads to more severe lung disease
The third genetic modifier of lung disease in CF (things that make CF lung function worse) is ___, which encodes transforming growth factor beta
It has a role in regulating ________ and tissue __________
The third genetic modifier of lung disease in CF (things that make CF lung function worse) is TGFB1, which encodes transforming growth factor beta
It has a role in regulating inflammation and tissue remodelling
True or False
A decrease in TGFB1 expression causes worse lung function in CF patients
False
An increase in TGFB1 expression causes worse lung function in CF patients
Intestinal obstructions in CF can be contributed, by an lateration of intestinal contatnts and formation of viscous meconium, to ____
MSRA
MSRA has a role in modifting intestinal ________
enzymes
_______ may have a arole in proliferation and function of beta cells of pancreatic inlets
TCF7L2
May modify risk for diabetes in CF patients who have not had recent or prolonged exposure to systemic steroids
Women generally have ___ outcomes with CF
poorer
May relate to eating less (you need to eat alot if you have CF)
What are some other things that mean worse outcomes for CF patients?
low-socioeconomic status
Exposure to tobacco smoke - active and passive
infectious exposures
Disease self-management
IRT stands for
Immunoreactive trypsinogen
Sweat tests are usually at __ weeks of age (if they’re needed, one mutation only)
6 weeks
only __% of eligible relative actually have cascade testing
12%
Lack of communication
True or False
Pre-implantation genetic testing (using IVF) is a means for carrier couples to implant unaffected embryos
True
