Pgx Basic Concepts II

Question 1

Allele

Answer 1

DNA sequence at a locus of one of the two homologous chromosomes

Question 2

Genotype

Answer 2

combination of alleles at the same locus of the homologous chromosomes in a genome/cell

Question 3

Homozygote

Answer 3

individual that has a pair of identical alleles at the locus

Question 4

Heterozygote

Answer 4

individual that has two different alleles at the locus

Question 5

Hemizygote

Answer 5

one allele is present, another allele is missing/deleted

also a heterzygous

Question 6

Mendel’s Law

Answer 6

each of the parents passes a randomly selected allele (1 of the 2 homologous chromosomes) to the offspring –> Law of Segregation

Question 7

Types of Polymorphisms

Answer 7

• SNP
• CNV
• Indel

Question 8

Single Nucleotide Polymorphism

Answer 8

• a single nucleotide is changed to another
• most common sequence variation that accounts for 90% of variations
• 1 SNP for every 300-750 base pairs
• many of us contains SNP but they are located in the intron or a non-important location cause little to no functional affects

Question 9

Reference Sequence that is compared to patients

Answer 9

• database that takes into account SNP where they survey lots of individuals and find the most popular/common SNP

Question 10

Types of SNP in the coding region (cSNP)

Answer 10

Non-synonymous: changing amino acid in protein
- Missense SNP
- Nonsense SNP

Synonymous: does not change amino acids
- Silent SNP

Question 11

Missense SNP

Answer 11

amino acid substitution (changes 1 AA to another AA)

Effects: gain or loss of function

Question 12

Nonsense SNP

Answer 12

amino acid is changed to a stop codon (UGA, UAA, UAG)

Effect: loss of function

Question 13

Silent SNP

Answer 13

does not change amino acids and therefore does not change gene/protein function

Question 14

Noncoding Region SNP

Answer 14

• intronic SNP
• SNP in gene flanking region
• SNP in UTR region

Question 15

Copy Number Variation (CNV)

Answer 15

• a DNA region has 0 to n copies in a population
• structural variation
• makes each chromosome longer or shorter
• 1 kb to several Mb

Effect: gain of function

Question 16

Example of CNV

Answer 16

CYP2D6 –> 0-13 copies

if 0/0: cannot metabolize certain drugs

1/6: metabolizes certain drugs at much faster rate –> increase the dose

Question 17

Insertion/Deletion (Indel)

Answer 17

• nucleotide present or absent from locus
• can be 1 to N nucleotides
• single Indel are is a specific form of SNP
• large Indel are CNV’s

INSERTION AND DELETION OF < 3 NUCLEOTIDES CAUSES A FRAMESHIFT OF THE OPEN READING FRAME LEADING TO A TRUNICATED PROTEIN

Question 18

Trunicated Protein

Answer 18

loss of function

Ex)
- Indel
- nonsense SNP

Question 19

Website for Nomenclature

Answer 19

pharmgkb.org

Question 20

rs number

Answer 20

reference SNP

ID used for SNP’s

Question 21

MDR1 G2677T

MDR1 2677G>T

Answer 21

a G to a T polymorphism at the nucleotide position 2677 of mRNA

Question 22

CYP4AF2 V433M

CYP4AF2 433V>M

CYP4AF2 Val433Met

Answer 22

Val to Met amino acid polymorphism at the position 433 on the protein sequence

Question 23

c. 1297G>A

Answer 23

count from the first nucleotide of the CODING DNA sequence (start codon: AUG)

Question 24

p. Val433Met

Answer 24

protein position

Question 25

Human CYP2C19*17

Answer 25

Species: Human Superfamily: CYP Family: CYP2 Subfamily: CYP2C Allele/Haplotype: *17 ITALICIZED: gene/allele REGULAR + PERIOD: protein

Question 26

CYP2C19 Allele Nomenclature

Answer 26

CYP2C19*1A - no change - no SNP - normal function CYP2C19*2D - splicing defect - c. 99C>T - loss of function CYP2C19*3A - nonsense - p. W212X - loss of function CYP2C19*17 - missense - p. I331V - gain of function