Genome, Genes, and Molecular Medicine

Question 1

Customized medicine takes into account the relationship between

Answer 1

Genomic sequence and treatment outcome

Question 2

__ is important for customized medicine

Answer 2

Analysis of gene expression profile

Question 3

What is the significance of DNA sequence in terms of healthcare?

Answer 3

DNA sequence is important for

• Designing treatment options
• Providing a rationale for treatment options
• Comparing individuals and species to allow for better understanding of disease mechanisms

Question 4

Difference between humans and chimpanzees in terms of DNA(3)

Answer 4

35 million single nucleotide changes

5 million insertion/deletion changes

Various chromosomal rearragements

Question 5

Humans vs. chimpanzees- malaria- humans are more susceptible to ___ chimps are more susceptible to ___

Answer 5

Humans: plasmodium faciparum

Chimps: plasmodium reichenowi

Question 6

Humans lack ___ activity, whereas chimps don’t (i.e. what enzyme do humans lack that chimps have that makes humans and chimps susceptible to different kinds of malaria?)

Answer 6

CMP-N-acetylneuraminic acid hydroxylase (CMAH)

Question 7

What is the function of CMAH

Answer 7

Converts N-acetylneuraminic acid to N-glycolylneuraminic acid

Neu5Ac –> Neu5Gc

Question 8

What are Neu5Ac and Neu5Gc

Answer 8

2 common sialic acids found on the surface of mammalian cells

Neu5Ac = substrate
Neu5Gc = product

Question 9

P. faciparum binds to ___ while P. reichenowi binds to ___

Answer 9

Faciparum: Neu5Ac

Reichenowi: Neu5Gc

Question 10

Longevity of drug in the system depends on (4)

Answer 10

Absorption

Distribution

Metabolism

Excretion

Question 11

What can modify the factors that determine the longevity of a drug in the system

Answer 11

Genetic background or polymorphisms of relevant genes/proteins

Question 12

What is the function of cytochrome P450

Answer 12

Hydroxylation of xenobiotics which are then excreted

Question 13

CYP mediated reaction causes

Answer 13

Activation and formation of reactive oxygen

Question 14

CYP mediated reactions occur in

Answer 14

Liver

Intestine

Lung cells

Question 15

Ex: CYP2C9 (what does each character stand for?)

Answer 15

2 = family number

C = subfamily

9 = gene number within the subfamily

Question 16

What drug is metabolized by CYP2C9

Answer 16

Warfarin (coumadin)

Question 17

What is the function of warfarin/coumadin

Answer 17

Blood thinner

Question 18

Alleles that differ at specific places in their sequences are called

Answer 18

Single nucleotide polymorphisms (SnPs)

Question 19

What relationship does polymorphism have with drug dose?

Answer 19

Polymorphisms may alter the activity of the enzyme

Question 20

Increased bleeding with Warfarin occurs in patients with what CYP2C9 alleles?

These patients will require

Answer 20

CYP2C9*2

CYP2C9*3

Patients will require a lower dose of warfarin as comapred to CYP2C9*1 homozygous patients

Question 21

CYP2C92 or CYP2C93 isoforms may be ___ warfarin

Answer 21

Inactivating the drug slower than CYP2C9*1

Question 22

Coumadin inhibits

Answer 22

VKORC1 activity aka

Vitamin K epoxide reductase

Question 23

What is the function of VKORC1/Vitamin K epoxide

Answer 23

Converts vitamin K epoxide to reduced form of vitamin K

Question 24

What factors are vitamin K depndent

Answer 24

II, VII, IX, and X

Question 25

If coumadin remains in the system, what is the effect on vitamin K levels

Answer 25

Vitamin K levels will not be sufficient for coagulation reacitons

Question 26

What are the 2 polymorphsims that impact the effectiveness of coumadin

Answer 26

CYP2C9 allele

VKORC1 polymorphism

Question 27

DNA nucleotides are joined by

Answer 27

Phosphodiester bonds

Question 28

What forms the backbone of DNA

Answer 28

Sugar-phosphate backbone

Question 29

Uracil is the RNA equivalent of

Answer 29

Cytosine

Question 30

Nucleosides vs nucleotides

Answer 30

Nucloside = nitrogenous base + sugar

Nuclotide = nucloside + one more phosphate

Question 31

Phosphodiester bond is formed between

Answer 31

5’ phosphate of one nucleotide and 3’ OH of the next one

Question 32

Functions of nuclotides

Answer 32

Constituents of DNA/RNA

Cofactors in enzymatic reactions

Energy currency (ATP)

Cell signaling

Question 33

Griffith’s experiment

Answer 33

Defined DNA as the genetic material of cells (rat + heat killed strep pneumoniae experiment)

Question 34

Avery, McCary, and MacLeod experiment

Answer 34

Purified material in Griffth’s experiment as DNA

Question 35

Hershey and Chase experiment

Answer 35

Checked to see which component of a bacteriophage enters the bacteria during infection

Question 36

Gargaff’s Rules

Answer 36

A = T

C = G

Question 37

Types of dsDNA

Answer 37

A, B, and Z

Question 38

A for of dsDNA

Answer 38

Right handed

11 bases/turn

Question 39

B form of dsDNA

Answer 39

Right handed

10 bases/turn

Question 40

Z form of dsDNA

Answer 40

Left handed

12 bases/turn

Question 41

Most of the DNA seen in living things is

Answer 41

B form of DNA

Question 42

Denaturation of dsDNA = ___ order kinetics

Answer 42

Zero

Question 43

Renaturation of dsDNA = ___ order kinetics

Answer 43

Second

Question 44

ssDNA has a ___ absorbance of light

Answer 44

Higher

Question 45

What disrupts the DNA helix?

Answer 45

Heat (disrupts H bonds)

Urea and formamide

Question 46

What stabilizes the DNA helix?

Answer 46

High [Na+] [K+]

High GC/AT ratio

Question 47

Number of H bonds in AT vs GC

Answer 47

AT = 2 H bonds

GC = 3 H bonds