Lecture 9

Question 1

The carrier frequency (northern euro) is

Answer 1

1 in 25

Question 2

incidence of CF is..

Answer 2

1 in 2500-3000 live births

Question 3

people of Japanese ethnicity are at a ___ risk of CF

Answer 3

low

Question 4

There is some but variable correlation between class of mutation and phenotype, especially with ______ function

Answer 4

pancreatic function

Question 5

Classes __,__ and ___ (and probably __) usually have more severe lung disease and PI

Answer 5

Classes I, II and III (and probably VI)

Question 6

Classes IV and V usually associated with __and milder ___disease

Answer 6

Classes IV and V usually associated with PS and milder lung disease

Question 7

The clinical penetrance of R117H depends on another intragenic polymorphism. Examples are things like

Answer 7

male infertility (with borderline or elevated sweat chloride)

Question 8

Twin studies can be used to look at concordance in MZs and DZs for clinical features - to estimate _____ _____

Answer 8

genetic control

Question 9

What are the reasons to identify genetic modifiers?

Answer 9

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)

Question 10

How do you identify a genetic modifiers?

Answer 10

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

Question 11

What are the limitations of Gonome wide association studies?

Answer 11

When genes are less penetrant, they need greater sample size

need to replicate studies for validation

need to demonstrate correlation

Question 12

EDNRA encodes _____ receptor type _

Variants of this alter ____ ______ ____ in airways and/or vasculature and therefore may modify CF lung disease

Answer 12

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

Question 13

_____ 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

Answer 13

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

Question 14

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 __________

Answer 14

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

Question 15

True or False

A decrease in TGFB1 expression causes worse lung function in CF patients

Answer 15

False

An increase in TGFB1 expression causes worse lung function in CF patients

Question 16

Intestinal obstructions in CF can be contributed, by an lateration of intestinal contatnts and formation of viscous meconium, to ____

Answer 16

MSRA

Question 17

MSRA has a role in modifting intestinal ________

Answer 17

enzymes

Question 18

_______ may have a arole in proliferation and function of beta cells of pancreatic inlets

Answer 18

TCF7L2

May modify risk for diabetes in CF patients who have not had recent or prolonged exposure to systemic steroids

Question 19

Women generally have ___ outcomes with CF

Answer 19

poorer

May relate to eating less (you need to eat alot if you have CF)

Question 20

What are some other things that mean worse outcomes for CF patients?

Answer 20

low-socioeconomic status

Exposure to tobacco smoke - active and passive

infectious exposures

Disease self-management

Question 21

IRT stands for

Answer 21

Immunoreactive trypsinogen

Question 22

Sweat tests are usually at __ weeks of age (if they’re needed, one mutation only)

Answer 22

6 weeks

Question 23

only __% of eligible relative actually have cascade testing

Answer 23

12%

Lack of communication

Question 24

True or False

Pre-implantation genetic testing (using IVF) is a means for carrier couples to implant unaffected embryos

Answer 24

True