Second half of genetics-exam review

Question 1

gene therapy and HIV

Answer 1

Berlin patient cured of HIV after receiving HSC transplant from CCR5 negative donor. zinc finger nucleases used to disrupt the CCR5 gene in HSC to treat HIV - the virus binds to CCR5 and CD4 to enter host cell

Question 2

gene therapy and cancer

Answer 2

1. replace missing tumor suppressor genes
2. block expression of over active oncogenes
3. insert suicide genes
4. insert genes to induce anti tumor immune responses
5. express genes which impede tumor neo vasculature
6. add chemotherapy resistance genes to HSC to allow chemo dose intensification

example of 4)
chimeric antigen receptors CARs- get T cells to recognize cancer cell as foreign and kill it
suicide gene therapy - enzyme that activates a non toxic drug to toxic compound. then treat body to non toxic drug and only cells that have the enzyme will be killed by it

Example of 3) herpes implex virus TK-activates ganciclovir to cytotoxic compound

Question 3

What re the findings from GWAS studies of psych disorders?

Answer 3

• schizophrenia has larger number of genome wide significant loci
• genetic risk factors for bipolar disorder are similar to schizophrenia except in MHC genes and histone gene clusters (schizo only)
• high genetic correlation between schizophrenia and bipolar disorder, moderate between schizo and major depressive, moderate between bipolar and depressive

Question 4

What are the organs primarily affected by mitochondrial disorders?

Answer 4

Skeletal muscle, heart, brain, endocrine, renal involvement, hearing and vision loss

Question 5

What are the general principles in managing mitochondrial disorders?

Answer 5

1. increase energy supply: exercise (but not over exert), cofactors (coQ, carnitine, creatine, etc.)
2. decrease energy demand: avoid fasting, avoid high demand situations, avoid steroids
3. protect mitochondria from reactive oxygen species, use anti oxidants

Question 6

How are mitochondrial disorders transmitted?

Answer 6

maternally. In a pedigree, mother with disease will pass it to all her children.

Question 7

What is uniparental disomy (UPD) and what diseases can arise as a result if the regions are imprinted?

Answer 7

UDP is when a person receives two copies of a chromosome or part of a chromosome from one parent only

• Angelman Syndrome- 2 paternal copies of UBE3A
• Prader-Willi Syndrome-2 maternal copies
• Beckwith Wiedemann Syndrome-2 paternal copies of IGF2

Question 8

How can epigenetics be used in cancer therapy?

Answer 8

• drug inhibitors of epigenetic regulators to reverse silencing of tumor suppressor genes
• inhibitors of HDACs -histone acetylation erasers
• inhibitors of DNMTs-DNA methylation writers
• Vidaza-only drug that’s shown survival benefit to patients with myelodysplastic syndrome

Question 9

What are the 5 general principles of metabolic disorders?

Answer 9

1. rare but together common. Most doctors miss them.
2. Disease b/c
   - too much metabolite before block (intoxication)
   - too lil metabolite after block (deficiency)
   - both
3. Can be acute and life threatening. early onset day 2-5, late onset present in toddlers with common viruses
4. limited ways newborns can express themselves, same symptoms seen is common infections-crying, vomiting, feeding refusal
5. most are autosomal recessive, negative family history, consanguinity present in minority.