Lecture 11: Personalized Medicine and Pharmacogenomics

Question 1

Genes involved in drug metabolism fall into a list called ADME core markers. What does ADME stand for?

Answer 1

Absorption, distribution, metabolism, & excretion

Question 2

Using the example of an indiv’s genotype for CYP2D6 in examining an individual’s ability to metabolize certain drugs, describe the following classes of function in regard to metabolism:

• Extensive
• Poor
• Ultra
• Intmd

Answer 2

• Normal, expected function, 2 func alleles
• No func allele, enz activity very low, chemical accum’s, can be toxic, require lower dosage of drug
• Degradation of drug so rapid it’s elim’d before therapeutic levels can be reached; higher doses needed
• Heterozygotes with one func and one mutant allele, can utilize drug but at slower rate than normal, require a lower than nl dose to avoid toxic buildup

Question 3

In the case of pro-drugs the opposite phenomena occurs; Ultra-rapid metabolizers may suffer adverse events, and poor metabolizers may not respond. T or F?

Answer 3

True.

Question 4

By knowing the genotype with respect to the genes of interest for drug metabolism, it should be possible to make a better estimate of what?

Answer 4

The effective dose for each patient.

Question 5

What two genes have been studied that directly affect warfarin metabolism?

Answer 5

VKORC1 and CYP2C9

Question 6

Evidence of personalized medicine is seen in what things?

Answer 6

Drug therapy; Idiopathic Disease; Cancer Dx, Prognosis, & Tx; Prenatal Testing & Newborn Screening

Question 7

Combining Kary Anal, FISH, microarray, flow cytom, & hematopathology to obatin a unique set of clinical data for each patient is already part of what field of medicine?

Answer 7

Oncology

Question 8

A chip that has the potential to do a genome-wise scan of an indiv’s genetic complement, designed to detect genes for which tx is available and for which early tx may reduce the intensity of the disease phenotype, describes what type of technology?

Answer 8

Microarray.

Question 9

Microarray can notably detect what two things discussed in the notes?

Answer 9

22q microduplication syndrome and UPD. In regard to UPD, microarray of the genome will detect it without even suspicion of it initially. Also, it only requires the patient - don’t even need the parents - to detect regions of UPD aka regions of homozygosity.

Question 10

When intmd-sized regions of homozygosity (ROH) are seen, exceeding 5% of genome and appearing on multiple chrom’s, this is likely due to what phenomenon? Side note, this homozygosity isn’t detectable by any other means than MA.

Answer 10

Identity by descent (IBD).

Question 11

Although having large regions of homozygosity is not diagnostic of disease, it increases the likelihood of what?

Answer 11

Expression of a recessive disorder for genes within the regions.

Question 12

At the present time, there is not enough known about the whole genome to make a NGS study clinically useful. However, indiv panels of genes have been developed. For example: [Name 4]

Answer 12

• Mutations specific to one or more categories of cancer
• The currently known set of genes assocd with chrom microdels (Williams syn, VCFS, etc)
• Genes commonly assocd with birth defects
• The ADME core markers for drug metabolism

Question 13

Name 3 tests prenatal testing is composed of.

Answer 13

MSAFP, ASAFP, Maternal serum quad/integrated test

Question 14

For population screening, it is effective to look for diseases that are very rare. T or F.

Answer 14

False. The diseases should be clearly defined, treatable, and occur with a reasonably high population incidence.

Question 15

Key factors in carrier screening include what?

Answer 15

• The mutation must be in a reasonably high freq in population
• The test is suitable for mass screening
• Genetic counseling available to explain results
• PRENATAL TESTING AVAILABLE