Pharmacogenomics Quiz 1 Flashcards
1
Q
What is an “actionable signature”?
A
Information used to make a treatment decision
2
Q
As of 2018, how many pharmacogenomic drug labels have been approved by the FDA?
A
150
3
Q
As of 2023, how many pharmacogenomic drug entries have been approved by the FDA?
A
517
4
Q
What can genetic markers distinguish about patients?
A
-Who is most likely to respond to a drug
-Who is most likely to develop side effects
-Who should not take the drug
-The best dose they should take
5
Q
What is Pharmacokinetics (PK)?
A
What the BODY does to the drug
6
Q
What is Pharmacodynamics (PD)?
A
What the DRUG does to the body
7
Q
What are the 4 roles of a pharmacist in pharmacogenomics?
A
RECOMMENDING (or scheduling) pharmacogenomics testing to help with drug and dosage selection
DESIGNING patient-specific drug and dosage regimen based on their genetic profile that also considers the PK and PD of the drug
EDUCATING patients, pharmacists, and health care professionals about pharmacogenomics and indications for clinical pharmacogenomic testing
COMMUNICATING genetic drug therapy recommendations to the health care team (includes documenting interpretation of results in patient’s health record)
8
Q
What is an intrinsic factor?
A
A genetic/ physiological factor
(intrinsic to a person)
9
Q
What is an extrinsic factor?
A
An environmental factor
(extrinsic to a person)
10
Q
What are the 4 nucleobases of DNA?
A
Adenine (A)
Thymine (T)
Guanine (G)
Cytosine (C)
11
Q
What nucleobase bonds with Adenine (A)
A
Thymine (T)
12
Q
What nucleobase bonds with Guanine (G)?
A
Cytosine (C)
13
Q
How many hydrogen bonds form between Adenine (A) and Thymine (T)?
A
2 hydrogen bonds
14
Q
How many hydrogen bonds form between Guanine (G) and Cytosine (C)?
A
3 hydrogen bonds
15
Q
Which DNA base pairs bind more strongly to each other? A + T or C + G
A
C + G
A + T form 2 hydrogen bonds whereas C + G form 3 hydrogen bonds
16
Q
How many pairs of chromosomes do humans have?
A
23
17
Q
What is a genome?
A
An organism’s complete set of DNA (including all of its genes)
18
Q
How many DNA base pairs make up the human genome?
A
3 billion DNA base pairs
19
Q
A copy of the entire genome is contained where in the human body?
A
In all cells that have a nucleus
20
Q
How many base pairs are in a kilobase (kb)?
A
1000 bp
21
Q
How many base pairs are in a megabase (Mb)?
A
1 million bp
22
Q
How many total genes are found in the human genome?
A
21,000 (about 20,000)
*this is actually lower than previously expected, similar to the # found in mice
23
Q
What is a gene?
A
A sequence of DNA or RNA which codes for a molecule that has a function
-Made up of DNA
-Act as instructions to make molecules
**evolving concept
24
Q
What is a protein coding gene?
A
A gene that is expressed to be a protein
(type of classification of genes)
25
What % of the human genome are protein-coding sequences?
1-3%
26
What is a noncoding gene?
A gene who's final product is an RNA (not a protein)
27
What is a Transfer RNA (tRNA)?
RNA that transfers amino acids to the RNA template to make proteins
28
What is Ribosomal RNA (rRNA)?
The RNA component of a ribosome
29
*What is microRNA (miRNA)?
RNA that plays an important role in regulating protein-coding gene expression
30
True or False: Symbols for genes are italicized, but symbols for proteins are not
TRUE
*important part of gene nomenclature
31
True or False: DNA always has a promoter region
True
32
What is the function of the promoter region in DNA?
Determines what tissue the gene will be expressed in
33
What is the 5'UTR in DNA and what is its function?
(5' Untranslated region)
Has a regulatory function
(if some cells need more of a protein or less of a protein, or need a protein to go to a certain location, this region regulates it)
34
Where is the 5'UTR found?
Exists in DNA and mRNA but NOT IN PROTEIN
35
Which region is removed to make mRNA and eventually, a protein?
(Intron or Exon)
Intron (non-coding)
-exons (coding) remain and are eventually made into proteins
36
Which region is a coding region that contains information to encode a protein. This region is not removed from a gene.
(Intron or Exon)
Exon
37
What is the professor's favorite gene?
SCN2A
38
Note:
Review Lecture 2 Slide 9
39
What is a sequence position?
The unique position of a nucleotide in the reference genome
(The starting point and ending point of a gene in the genome)
(location of a gene)
40
What is a locus?
The unique position of a nucleotide in the reference genome
(similar to sequence position)
41
What is chromatin?
Unwound DNA with proteins
(accessible for transcription)
42
What is a chromosome?
Tightly packed DNA
43
How does packing/unpacking DNA affect gene expression?
If you want to express only one gene, you have to unpack DNA
(otherwise it is too tightly packed to only do one)
44
How many chromosomes does a human have?
46
(23 pairs)
45
What is a non-sex chromosome called?
Autosome
46
What is a karyotype?
A complete picture of the genome in a cell
(done on unborn fetuses to detect for disease)
47
Why are chromosomes paired up into homologous chromosomes?
-One chromosome comes from the mother and one from the father and they pair
-Main reason is to increase genetic diversity of the population to increase survival
48
What disease has the first CRISPR medication been developed to target?
Sickle cell disease
49
How is genetic information expressed (AKA Central Dogma) (what is the pathway it takes)?
Previous thinking:
DNA (replicates) -> Transcription -> RNA -> Translation -> Protein
Now:
-DNA replicates and is transcribed to RNA
-Transcription is reversible!
-RNA is able to replicate and then is translated to protein
-Protein replicates itself through prion
*see Lecture 2 Slide 14
50
What is the process of changing DNA to RNA?
Transcription
*reversible
51
What is the process of changing RNA to protein?
Translation
52
True or False: RNA is less stable than DNA
TRUE
53
What process of the central dogma results in the creation of viruses such as coronavirus?
RNA replication
(RNA is less stable than DNA, more likely to have mutations and change when it replicates)
*coronavirus is an RNA based virus and does not have DNA
54
Instead of a Thymine (T) nucleobase, what is present in RNA instead?
Uracil (U)
55
What is missing in a matured mRNA?
Introns
56
When matured mRNA is formed, where is it exported to?
Exported from the Nucleus to the Cytoplasm
57
When DNA is transcribed to matured mRNA, what intermediate form is it changed to first?
mRNA precursor
**introns have not yet been cut out but are starting to
58
What is the start codon?
AUG
(ATG in DNA)
59
What amino acid does the start codon (AUG) code for?
Methionine
60
What is the "open reading frame"?
The sequence from the start codon to the codon before the stop codon
61
What is a "premature stop"?
When a protein has a stop codon in the wrong place
-causes the reading frame to stop prematurely and leads to disease
62
True or False: Only the first ATG is the start codon
True
-if there is another ATG in the sequence, it is not a start codon
(only the first ATG starts a protein)
63
True or False: Any UAA, UAG, OR UGA us a stop codon regardless of its position in a sequence
TRUE
-anytime one of these codons appears, it is a stop codon
-there should not be any of these codons in the middle of a protein (otherwise it is a "premature stop")
64
How many total codons are there?
64
65
How many amino acids are there?
20 amino acids
66
What is a benefit of having multiple codons code for the same amino acid?
Increases resistance to genetic changes
67
What is a polymorphism?
A sequence variation at the same position in homologous chromosomes
-influences diversity and adaptability of humans to a changing environment
68
Can polymorphisms affect the genome of single germ cells (haploid cells)?
NO
-only affect homologous chromosomes and occurs in both
69
True or False: all polymorphisms cause disease
False, only cause disease when they affect the function of a protein
70
What is a Single Nucleotide Polymorphism (SNP)?
A single nucleotide is changed to another
*most common DNA sequence variation
*often changes the amino acid coded for
(ex: A changed to C in a codon)
(ex: CTA changed to CTC)
71
*What is an allele?
The DNA sequence at a locus of ONE of the two homologous chromosomes
(each chromosome can have a different or identical version of the allele)
72
*What is a genotype?
The combination of alleles at the same locus of the homologous chromosomes in a genome/cell
73
What is a homozygote?
An individual that has a pair of identical alleles at the locus
(genotype is homozygous)
74
What is a heterozygote?
An individual has two different alleles at the same locus
(genotype is heterozygous)
75
What is a hemizygote?
An individual where one allele presents while the other allele is missing on the other chromosome
(genotype is hemizygous)
*their genotype is also considered heterozygous
76
What is Mendel's Law (of segregation)?
Every individual possesses two alleles and each parent passes one of them (randomly selected) onto the offspring
77
What is the most common DNA sequence variation/ polymorphism?
Single nucleotide polymorphism (SNP)
(>90% of all genetic variations)
78
What are the two types of Single Nucleotide Polymorphisms (SNPs) that can occur in the coding region (cSNP)?
Non-synonymous SNP
Synonymous SNP
79
What is a non-synonymous SNP?
A single nucleotide polymorphism where the amino acid is changed in the protein
80
What is a synonymous SNP?
A single nucleotide polymorphism where a change in a nucleotide does not result in a change in the amino acid coded for
-the gene/protein function is normally not changed
(silent SNP)
81
What are the 2 types of non-synonymous SNPs?
Missense SNP
Nonsense SNP
82
What is a Missense SNP?
A nucleotide change leads to an amino acid substitution
(but does not change to a stop codon)
(either leads to gain- or loss-of-function for the protein depending on what amino acid it changes to)
83
What is a Nonsense SNP?
A nucleotide change leads to an amino acid being changed to a stop codon
(normally leads to loss-of-function only!)
84
True or False: You can look at a codon and tell if it is gain- or loss-of-function
FALSE
-You cannot tell just by looking at it!!
*Have to check its function!
*ONLY can tell if it is missense or nonsense, nonsense is typically loss-of-function
**IF THERE IS A QUESTION ON THE EXAM asking about missense SNP and whether it is gain- or loss-of-function, the answer is: need more information
85
If a question on the exam gives you a missense SNP and asks if it is gain- or loss-of-function with no other information, what is the answer?
NEED MORE INFORMATION
-cannot tell without information about how it is functioning
86
If a question on the exam gives you a nonsense SNP and asks if it is gain- or loss-of-function, what is the answer?
Loss-of-function
87
True or False: Many newborns require both alleles to have a mutation in order to develop a disease
True
88
What is a truncated protein?
A protein that has been shortened by a nonsense SNP mutation
89
What is a copy number variation (CNV)?
Sections of the genome are repeated and the number of repeats varies between individuals
-A DNA region (a part or even one or more entire genes) has 0-n copies in a population
90
How does copy number variation (CNV) affect the way a patient metabolizes a drug?
-Can change the number of enzymes a patient has to metabolize a drug
(0 copies= patient cannot metabolize a drug)
(Many copies (ex: 7)= patient metabolizes drug too fast)
91
What is an insertion/deletion polymorphism (Indel)?
An extra nucleotide is added or deleted from a locus
-Can be 1 to n nucleotides
**this is very bad because it changes the reading frame (frameshift) and affects all amino acids after it
-Can be an SNP
-Large ones are CNVs
92
What affect does a frameshift have on the resulting protein?
Often leads to a truncated (loss-of-function) protein for degradation
93
What is the only scenario in an insertion/deletion (Indel) polymorphism where a frameshift does not occur?
When 3 nucleotides are added or deleted (or any multiple of 3)
-in this case, an amino acid is inserted or deleted without affecting the others downstream
94
What are the parts of the nomenclature of a gene?
Species -> Superfamily -> Family -> Subfamily -> Isoform -> *Allele/haplotype
EX: Human CYP2C19*17
Species: Human
Superfamily: CYP
Family: 2
Subfamily: C
Isoform: 19
Allele/Haplotype: *17
*Note: this entire thing should be italicized
*Note: GENE NAME only includes: Superfamily, Family, Subfamily, and Isoform
95
Regarding nomenclature, what should be italicized?
Gene/ allele name
**not a protein name!!
96
Regarding nomenclature, when would we use a * vs a .
For genes/alleles: use a *before the allele/haplotype
For proteins: use a . before the allel/haplotype
Ex Gene: *italicized* CYP2C19*17
Ex Protein: CYP2C19.17
97
*Note
Review lecture 3 slide 18 for nomenclature
98
What does a * in the nomenclature refer to?
A certain SNP that is present that results in a certain functional change
99
What is an ultrarapid metabolizer?
A patient who metabolizes a drug with normal or increased activity
100
What genotype results in an ultrarapid metabolizer?
Two increased activity alleles (*17/*17)
or
One functional allele + one increased-activity allele (*1/*17)
101
What is an extensive metabolizer?
A patient who metabolizes a drug with homozygous wild-type or normal activity
102
What genotype results in an extensive metabolizer?
Two functional alleles (*1/*1)
103
What is an intermediate metabolizer?
A patient who metabolizes a drug with heterozygous or intermediate activity
104
What genotype results in an intermediate metabolizer?
One functional allele + one loss-of-function allele (*1/*2-8)
One loss-of-function allele + one increased-activity allele (*2-8/*17)
105
What is a poor metabolizer?
A patient who metabolizes a drug with homozygous variant, mutant, low, or deficient activity
106
What genotype leads to a poor metabolizer?
Two loss-of-function alleles (*2-8/*2-8)
107
What is the Increased Activity Allele?
*17
108
What is the Functional Allele?
*1
109
What are the Loss-of-Function Alleles?
*2-*8
110
What mutation does CYP2C19*1A correlate to?
(note the *1A)
None, no change in gene
-Normal function
111
What mutation does CYP2C19*2D correlate to?
(note the *2D)
Splicing defect
Loss-of-Function
112
What mutation does CYP2C19*3A correlate to?
(note the *3A)
Nonsense (stop codon)
Loss-of-function
113
What mutation does CYP2C19*17 correlate to?
(note the *17)
Missense (point mutation)
Gain-of-function
114
What is "Minor Allele Frequency"
The frequency that an unlikely phenotype (ultrarapid metabolizer, extensive metabolizer, etc.) appears in the population
-know how to calculate
-expressed as a %
115
What number represents the number of homologous chromosomes when calculating allele frequency?
For a given population of N individuals, the number of homologous chromosomes is 2N
(each individual has 2 homologous chromosomes paired)
116
What is the equation for Allele Frequency?
N= Q+R+S
N= # of individuals in population
Q= Number of homozygous people with one allele (T/T)
R= Number of heterozygous people (T/C)
S= Number of homozygous people with other allele (C/C)
117
How do we find the % of an allele in a given population?
First: Find the total number of the allele
Ex: T allele= 2Q + R
(Q= # of people with T/T
and
R= # of people with T/C)
Next: Find the % of the allele in the total population
Ex: T allele % = (2Q+R)/2N
N= number of individuals in the population
(note: 2N = the total number of homologous chromosomes/alleles in the population since each person has 2)
118
What is the equation to calculate Minor Allele Frequency? (AKA an Allele %)
Allele% = Homozygote % + (1/2) Heterozygote %
*note: must know the genotype frequencies to do this
119
True or False: Allele frequencies usually stay stable in a population
True
120
True or False: A rare allele in one population can be a common allele in another population
True
121
What is a haplotype?
A group of genes within an organism that were inherited together from a single parent
**Also refers to the inheritance of a cluster of single nucleotide polymorphisms (SNPs)**
122
What is linkage disequilibrium (LD)?
Non-random association of alleles at different loci on the same chromosome
123
When there is infinite recombination, how does this affect linkage disequilibrium?
No Linkage Disequilibrium
(distance between two loci is so long that every time recombination occurs, they will be recombined a lot of the time. Almost independent segregation occurs)
124
When there is no recombination, how does this affect linkage disequilibrium?
Complete/Perfect Linkage Disequilibrium
(distance between two loci is so short that every time recombination occurs, they are always switched together 100% of time, never recombined)
125
When recombination occurs in a portion of chromosomes, how does this affect linkage disequilibrium?
Incomplete Linkage Disequilibrium
126
What does R^2 measure regarding Linkage Disequilibrium (LD)?
How strong the correlation is between two variables (strength of LD)
*varies from 0 to 1
127
What does an R^2 of 0 mean?
No Linkage Disequilibrium (LD)
128
What does an R^2 of 1 mean?
Complete/Perfect Linkage Disequilibrium (LD)
129
An R^2 of what value is considered a strong Linkage Disequilibrium (LD)?
> or = 0.8
