Clinical cases/drugs

Question 1

People with maple syrup urine disease have high urine levels of keto-acids and high serum levels of branched chain amino acids. How would you address this and why?

Answer 1

In the disease, branched chain amino acids can’t be degraded properly, so diet must be monitored very carefully

Question 2

In class III and IV cystic fibrosis, on the affected receptor, gly is replaced with asp and arg is replaced with his, respectively. How would these changes affect the receptor ?

Answer 2

Class III: Makes it more negatively charged

Class IV: Doesn’t change the charge, but bulky his R-group could affect structure

Question 3

Quinolone is a type of antibiotic that specifically targets topoisomerase II, inhibiting its ligase activity. How would this affect DNA structure?

Answer 3

It would prevent its ability to rejoin DNA strands after unwinding them, resulting in bits of cleaved DNA

Question 4

HIV is often treated with NRTI’s. NRTI’s are nucleoside analogs. How do these drugs work?

Answer 4

They are incorporated into the DNA chain upon replication, but do not allow replication to proceed because of their lack of 3’ hydroxyl groups

Question 5

Myotonic dystrophy is a disease that is caused by trinucleotide repeats caused by a “slippage” of DNA polymerase during replication. What is the phenomenon associated with its inheritance called?

Answer 5

Anticipation. Each successive replication causes additional “slips,” meaning progeny start out with more repeats and therefore have more severe symptoms

Question 6

Aicardi-Goutieres disease results from a mutation in genes including one that code for RnaseH. Why is this significant?

Answer 6

RnaseH is responsible for removal of primers during DNA replication. This would cause structural abnormalities in the DNA

Question 7

Turner syndrome is a x- chromosome monosomy disease. If normal people with two x normally have one inactivated anyway, why does Turner syndrome arise?

Answer 7

Some genes on the x escape inactivation and remain active. Total loss of one of the two chromosomes results in a gene dosage issue

Question 8

CMMRD is a disease that results from mutations in genes that code for, among others, MutS, L, and H. What process are these proteins important for?

Answer 8

Mismatch base repair

Question 9

Xeroderma pigmentosum is a rare disease that affects what type of DNA repair?

Answer 9

Nucleotide excision repair as a result of thymidine dimers

Question 10

What is the mechanism of action of rifampicin?

Answer 10

It inhibits the formation of the first phosphodiester bond in transcription by binding to the prokaryotic RNA polymerase beta subunit

Question 11

What is the mechanism of alpha-amintin?

Answer 11

It inhibits eukaryotic RNA polymerase II

Question 12

B-thalassemia major is a disease in which a single point mutation in the thalassemia gene creates a splice site. How would this affect the disease form protein?

Answer 12

Results in a short non functional protein

Question 13

What is the process that affects abnormalities in CD44 that are associated with increased cancer risk?

Answer 13

Alternative splicing, causes certain gene variants to be inappropriately expressed

Question 14

In diseases involving mutations of the basic region of transcription factors, why would these mutations be a problem?

Answer 14

Affects the TF’s ability to bind DNA

Question 15

Rett syndrome results from a mutation in the MeCP2 gene. What process would this affect?

Answer 15

Regulation of gene expression via methylation

Question 16

Prader-willi is a disease resulting from ___ deletion of a ___ imprinted gene

Answer 16

paternal, maternal

Question 17

Angelman’s is a disease resulting from ___ deletion of a ___ imprinted gene

Answer 17

maternal, paternal

Question 18

How can uniparental disomy also cause Prader-willi or Angelman’s

Answer 18

UD happens when two chromosomes are inherited from a single parent and not the other. This would effectively lead to the same result as a deletion, since both copies of the same gene would be imprinted.

Question 19

What is unique about HCV and how its DNA is translated?

Answer 19

It doesn’t require a 5’ cap to be recognized and instead contains IRES which is recognized by the 40s/eIF3 complex

Question 20

On Philadelphia chromosomes + CML cells, the Bcr-ABL protein is overactive. What pathway is this pertinent to?

Answer 20

RTK pathway

Question 21

p53 is pleiotropic, meaning what? Why is this important?

Answer 21

It influences many seemingly unrelated functions. Mutations in p53 are therefore a large part in many cancer types