3

Question 1

SNPs

Answer 1

○ Synonymous - preserves AA sequence
○ Non-synonymous - does not preserve AA sequence

Both located in coding region of gene

Question 2

Insertion/Deletion

Answer 2

Question 3

Variable number tandem repeats (VNTR)

Answer 3

Question 4

Copy Number Variation (CNV)

Answer 4

Question 5

Somatic (gene mutations)

Answer 5

-Occurs in somatic cells during MITOSIS
-Passed down to other cells in the individual
-NOT passed down to individual’s offspring (not inherited)

*may or may not affect individual

Question 6

Polymorphism

Answer 6

A common genetic variation that occurs at a frequency of >1% in a population

*responsible for normal differences between people such as eye color, hair color, blood type, and also drug response

Question 7

Inherited (gene mutations)

Answer 7

Occurs in gene cells during meiosis
-passed onto offspring

Question 8

UGT1A1 gene

Answer 8

UGT1A1Gene Product: UDP-glucuronosyltransferase

*this liver enzyme converts unconjugated bilirubin to conjugated bilirubin, making it able to be dissolved/removed

Question 9

UGT1A1 PK

Answer 9

Question 10

UDP-glucuronosyltransferase is also the major route of ___

Answer 10

SN-38 elimination

SN-38 is the active metabolite of irinotecan used to treat colorectal cancer

Question 11

The *28 allele

Answer 11

is associated with reduced UGT1A1 expression and increased drug toxicity

Question 12

For N polymorphic sites,

Answer 12

there can exist up to 2^N theoretical haplotypes

Question 13

Inherited variants can be identified in DNA extracted from ____

Somatic mutations are found ____

Answer 13

ANY cell in the body

only in the somatic cell where the mutation occurred or their descendent cells

Question 14

Genotyping For Inherited Gene Variants

Answer 14

1. Identify genetic variants by DNA sequencing
2. Develop assay to screen patients for their genotypes (PCR, microarrays, sequencing, SNP arrays)

Question 14

PCR

Answer 14

Amplifies a single/few copies of DNA fragment

i. To genotype a couple of SNPs or samples
ii. Uses fluorescent dyes for A, C, G, T
iii. Heterozygotes will show a mixed signal for a nucleotide

Question 15

Custom SNP array

Answer 15

i. To genotype <300 SNPs
ii. Various techniques

Question 16

DNA microarray

Answer 16

To genotype 1000s of SNPs or samples

1. Isolate, label sequence
2. Run sequence over probe wells (each well has unique oligonucleotide probes)
3. Isolated seq. only stick to complementary probes
4. Wash wells
5. Scan wells for detection

Question 17

Sequencing

Answer 17

i. Entire genome is sequenced to identify genotype
ii. Can be costly
iii. Alternatively, exome sequencing, which is just sequencing of exons

Question 18

Screening For Somatic Gene Variants

Answer 18

● Must collect DNA from the target tissue (note that not all cells in the target tissue will have the mutation)
● Must sequence entire genome of cell to find mutation
● Alternatively, can sequence only functional region of gene

Question 19

KRAS

Answer 19

● Activated by EGFR
● Common cancer drugs cetuximab and panitumumab block EGFR
● But if there’s a mutation in KRAS (to be ON permanently) that allows it to function without EGFR, these drugs are
ineffective
● Somatic mutation that leads to a change in codon 12 (13)

SO blocking EGFR with a monoclonal antibody will only be effective in tumors with normal KRAS