Lecture 9 - Clinical Genetics Flashcards
What is the pattern of inheritance of CF?
Autosomal recessive
Which ethnicity is most affected by CF?
Caucasian, mostly northern european
What is the incidence of CF?
1 in 2500-3000
Why is CF important?
Most common single genetic condition causing premature death in children of northern European descent
What is a possible selective advantage of heterozygotes for CF?
Postulated protection from cholera, typhus, asthma.
Describe the interaction between Salmonella and CF
The CF bacterium uses CFTR protein to gain entry to gut epithelial cells
In which ethnicities is CF prevalence very low?
Japanese population
What is often seen in CF pedigrees?
Absence of prior family history
‘suddenly appears’
This is because it is autosomal recessive
Describe the genotype-phenotype correlations in CF
Not as strong as one might think
• Pancreatic insufficiency in Class I-III mutations has strong correlation
What are class I-III mutations usually correlated with?
• Pancreatic insufficiency; very strong correlation
Also, to a certain degree,
• More severe lung disease
What are class IV-V mutations usually correlated with?
- Pancreatic Sufficiency (PS)
* Milder lung disease
Describe the interaction of the R117H mutation and other genotypes
Depending on the n° of T’s in cis to this mutation, the clinical penetrance is variable
R117H + 5T: will likely have disease causing mutation
R117H + 7T: unlikely to be a disease causing mutation
R117H + 9T: highly unlikely to act as a disease causing mutation
Describe Steven’s genotype and phenotype
Homozygous F508del
Less severe phenotype than Sean
What is the best way to do studies that want to determine environmental and genetic modifiers?
Monozygotic twin studies
What are the effects of genes and environment on lung function in CF?
50-50 genes and environment
What is meconium ileus?
To what degree is it affected by genes and environment
- Blockage in ileum of babies in utero by sticky, black faeces
- almost completely determined by genes
