MCP 6

Question 0

Name the type of disorder that one would use dietary modification to treat and an example?

Answer 0

Metabolic disorders, - classic examples include amino acid catabolism disorders
PKU restricted bland diet that is life long

Question 1

What are two intial categories of intervention for medical concerns sometimes genetic diseases ?

Answer 1

Medical and surgical interventions
Medical includes drug therapy treat symptoms
Surgical - cleft palate repair or transplant surgery

Question 2

How would you treat abnormal PKU ?

Answer 2

Supplementation with the missing enzyme

Also called replacement - ex BH4

Question 4

What is it called when you divert pathway to treat a disorder?

Answer 4

Diversion directing a pathway in another direction to avoid substrate accumulation for urea pathway use sodium benzoate will combine ammonium with glycine to make hippurate which excreted in urine

Question 5

Name two other treatments for metabolic disorders

Answer 5

inhibition and depletion

Question 6

Define Inhibition treatment

Answer 6

modifying the rate of synthesis by using a drug or other agent that slows or blocks a critical step in the pathway

Question 7

define depletion treatment and give an example

Answer 7

removal of a substance that is excess
-hereditary hemochromatosis is the excess accumulation of iron in the blood and can be relieved by regular blood letting or phlebotomy

Question 8

Treatment at the protein level

Answer 8

replacement -extra cellular -> if a protein is absent add it back (ex; hemophilia A- factor VIII, or alpha 1 antitrypsin deficiency-treat with alpha 1 antitrypsin)

Question 9

Problems with treatment at the protein level?

Answer 9

cost (have to give many repeated treatments as it is not a permanent fix), availability (may come from animal sources), antibody production in patient and contamination

Question 10

Treatment at protein level intracellularly issues

Answer 10

replacement must target a specific cell type -> can be very challenging to get it to the right target

Question 11

Explain treatment at a protein level-enhancing genetic expression and give an example

Answer 11

use of one gene to compensate for the mutation in another
example is sickle cell anemia-> treatment with decitabine increases level of gamma globin in blood which hypermethylates DNA (inhibits methyltransferase) and subsequently turns gamma globulin on -> upregulates HbF which upregulates oxygen carrying -inhibits polymerization of deoxyhemoglobin S

Question 12

Bone marrow transplantation -uses and process

Answer 12

• hematological disorders
• remove the disease clone and replace it with unaffected cells
• collect bone marrow stem cells fro the patient (autologous) or from matched donor (allogenic)
• transplant cells will re-established in the new host and hopefully cure the disease

Question 13

What method of treatment is commonly used in lysosomal storage diseases and why?

Answer 13

• bone marrow transplants -> bone marrow is about 10% of the bodys cell mass and extracellular transfer from the normal marrow may stimulate function in other cells
• acts as a source of mononuclear phagocytes
• can reduce the size of various internal organs
• if done within the first 2 years of life will limit the negative effects of neurological ill effects of disease

Question 14

define stem cells-

Answer 14

• self renewing undifferentiated cells

- can proliferate and produce a wide variety of different types of differentiated cells

Question 15

Name the two categories of stem cells and their properties

Answer 15

• embryonic SC = pluripotent and capable of differentiating into any cell type in the body
• somatic SC = self renewing but can only differentiate into cell types found in the tissue of origin

Question 16

What are some problems with allogenic stem cell use?

Answer 16

-immunosupressive drugs required to combat the possibility of graft vs host disease

Question 17

What are iPS?

Answer 17

induced pluripotent stem cells-> cells collected from an individual and are treated in vivo with “reprogramming factors” to make them into pluripotent state and undo differentiation

Question 18

Problems with nuclear transfer (cloning) and potential beneficial uses ?

Answer 18

• possible negative effects on genes->they may appear to be the age of the donor instead of the newly freshly minted genes found in embryos -> causing complications and early death as in the case of the dolly the lamb
• potential benefits agriculture, both crops and herds-> selecting for the most genetically hardy crop and most milk producing cow etc.

Question 19

When do we use nuclear transfer in humans?

Answer 19

-When there is an issue with a woman’s egg (carries cytoplasmic deleterious effects) we can extract the donor DNA and input the mother to be’s DNA and use the father’s sperm to fertilize the egg

Question 20

Issues with “My friend again” other animal/pet cloning companies?

Answer 20

• may not actually look identical

- things like size, personality can be totally different (personality is a learned behavior, not genetic)

Question 21

Define gene therapy

Answer 21

• incorporating “normal” functioning genes into the genome
• The deliberate introduction of genetic material into the human somatic cells for therapeutic, prophylactic or diagnostic purposes

Question 22

What are three general classes of gene therapy usage?

Answer 22

1. correcting a loss of function mutation by incorporating a functional gene into the genome
2. compensating for a deleterious dominant allele by replacing or inactivitating mutant allele
3. Adding genetic material that has a pharmacological effect

Question 23

What are some requirements for a successful gene therapy?

Answer 23

• identification of gene
• availability of gene sequence or cloned DNA from the gene of interest
• identification of target tissue
• ability to deliver gene to target
• understanding of gene biochemistry
• understanding of expression

Question 24

What is the biggest limitation of gene therapy ?

Answer 24

• delivering the gene to a target!
• vector must be able to carry the DNA
• must be able to insert the DNA into a target tissue
  
  • usually we use viruses - we can also use liposomes-> can create artificial liposome that carries DNA of interest can go through lipid bilayer and release DNA into cytoplasm once it fuses with lipid membrane (temporary)

Question 25

What are the two major categories of gene therapy introduction/

Answer 25

• in vivo = genes are incorporated into vectors and targeted to specific cells in body
• ex vivo = cells are extracted from the patent and genetically modified- the altered cells are returned back to the patient

Question 26

Who should participate in gene therapy treatment?

Answer 26

-individuals with known disease causing mutation but who currently show no symptoms?
-an individual with clinical symptoms of a disease but whom has received standard therapy?
-an individual who has failed standard therapy?
jury is still out-> only those patients who had failed conventional therapy and who had less than 3 months to live were accepted onto new protocols

Question 27

Antisense DNA therapy

Answer 27

antisense RNA will bind to its homologous sequence and prevent binding of ribosomes etc, thus blocking translation

• useful to down regulate protein production
• cancer characterized by overproduction of a protein
• incorporate an antisense strand into the cells to block translation

Question 28

RNA interference

Answer 28

• targets mRNA and cuts it up-> thus preventing the production of abnormal proteins, active unit small interfering RNA (siRNA) can be injected or incorporated into cells via vectors
• target degradation of mRNA
• destroy mRNA from negative dominant mutations while leaving the second allele alone
• reduces the concentrations of an mRNA that is over expressed

Question 29

Name and describe main vector for gene therapy

Answer 29

AAV- adeno-associated virus

• non pathogenic vector
• reduces the likelihood of an immune reaction
• is found in many serotypes-so that the proper vector can be matched to a particular cell type
• non-integrative so will not disrupt cancer genes