Treatment of Genetic Disease Flashcards
Potential issues with treatment (6)
- Haven’t identified causative allele or don’t know what it does
- Fetal damage before diagnosis
- Severe phenotypes-no way of fixing
- Dominant negative alleles-screws up the good one
- Treating one symptom may allow unforeseen symptoms to manifest
- Different mutations in the same gene may require different treatments
Inborn errors of metabolism (8)
- PKU
- Galactosemia
- MUSD
- Congenital hypothyroidism
- Biotinidase deficiency
- Urea cycle disorders
- Marfan syndrome
- Familial hypercholesteremia
How is PKU treated?
- Substrate reduction
- restrict diet
- take protein drink with everything except F
How is monogenic congenital hypothyroidism treated?
- replacement
- doesn’t produce thyroxine
- give thyroxine
How is ornithine transcarbamylase deficiency treated?
- diversion
- convert to something you can metabolize
How is familial hypercholesteremia treated?
- enzyme inhinbition
- statins-block HMG CoA reductase
How is Marfan Syndrome treated?
- receptor antagonism
- angiotensin II receptors
- losartan antagonizes angiotensin II receptor
How is hereditary hemochromatosis treated?
- depletion
- accumulate iron
- phlebotomy—remove RBCs from blood
How do you increase function of gene/protein through small molecules?
- administer chaperones
- often called heat shock proteins
- small molecule screens allows us to find effective treatments
How do you increase function of gene/protein through augmentation?
- enzyme replacement therapy
- Gaucher disease
- caused by betra glucocerebroside deficiency
- admininser beta-gluco twice monthly
How do you increase function of gene/protein through modulating gene expression?
- increase expression of normal gene that compensates for the effect of the mutation at another locus
- beta-thalassemia
- treat with hydorxyurea which increases fetal hemoglobin production in adults
How do you increase function of gene/protein through gene editing?
-CRISPR
Steps of CRISPR
- Create a guide RNA that matches the piece of DNA you want to modify
- Guide RNA is added to a cell along protein called Cas9 that cuts the DNA.
- Guide RNA homes in on target DNA and Cas9 cuts it out.
- Another piece of DNA is swapped into the place of old DNA and enzymes repair the cuts.
When do you use NHEJ with CRISPR?
With random mutations
When do you use HR with CRISPR?
- With specific mutations
- add in a template
