Pharmacogenomics Flashcards
(117 cards)
1
Q
Project ENCODE
A
ENCyclopedia Of DNA Elements
- collaboration of research groups funded by National Human Genome Research Institute (NHGRI)
2
Q
Project ENCODE
A
ENCyclopedia Of DNA Elements
- collaboration of research groups funded by National Human Genome Research Institute (NHGRI)
3
Q
Goal of ENCODE? How do they if a gene is active?
A
- build a comprehensive parts list of functional elements in the human genome
- including elements that act at the protein and RNA levels, and regulatory elements
4
Q
How many genes in a human?
A
20,000
5
Q
How many chromosomes?
A
23
6
Q
How many base pairs?
A
3 x 10^9 bp
7
Q
Relationship between chimpanzee and human?
A
96% homology; 120 x 10^6 bp difference
8
Q
Genome?
A
all the genetic material (DNA) of an organism
9
Q
Genetics?
A
the study of single genes and its effects
ex: cystic fibrosis, Hunting’s disease
10
Q
Genomics?
A
study of all the genes in the genome, including their interactions with environmental factors
ex: heart disease, asthma
11
Q
Pharmacogenetics?
A
study of genetic influences on an individual's response to drugs -specific gene, or group of genes to predict responses to a specific drug or class of drugs
12
Q
Pharmacogenomics? (large scale study)
A
study of all genes collectively that influence drug responses
- genome-wide analysis
13
Q
Genome-wide analysis?
A
identify genes in the search for novel drugs targets; key determinants of drug reactions
14
Q
How many bp in the human genome?
A
3 billion
15
Q
Pharmaceutical relevance of human genome?
A
16
Q
What makes pharmacogenomics easy today?
A
- The human genome sequenced
- ADVANCES in genome seq tech
- AUTOMATIZATION significantly reduced cost in seq
- COMPUTER TECHNOLOGY; handling data
17
Q
drug spec. trial and error?
A
- man drugs for certain illnesses
- not enough info about patient (so get info
- Drugs specified by trial and error (does it work, if not tweak it)
- side effects even unknown ones, serious ones
- FDA approval vis DRUG TRIALS
- drugs abandoned b/c of benefited population not convinced
18
Q
What can help avoid drug spec. trial and error?
A
Genome based characterization
19
Q
Cost of drug development?
A
$500 to $700 million
20
Q
Drug development timeframe?
A
12 years
21
Q
Time until patent expires?
A
7 years
22
Q
What is efficacy?
A
% patients cured at given dose
23
Q
What is toxicity?
A
% patients exhibiting side effects at a given dose
24
Q
Therapeutic index?
A
Dose range at which drug shows highest efficacy and low toxicity
25
List 9 of the top 10 causes of death in the U.S. that have genetic component?
```
1 Heart disease
2 Cancer
3 Cerebrovascular disease
4 Chronic lower respiratory disease
5 (Accidents/unintentional injuries)
6 Diabetes
7 Pneumonia/influenze
8 Alzheimer's disease
9 Kidney disease
10 Septicemia
```
26
What are factors the influence drug response?
- gender
- age
- body mass
- diet
- presence of other drugs
- disease
- exposure to certain
- chemicals or toxins
- genetic factors
27
What can you do to prevent gene-environment interactions?
- screening and medical recommendations
- exposure interventions or prevention to environmental factors
- target messages and interventions aimed at changing behaviors
28
Current impact of pharmacogenomics in Healthcare practice?
- pharmaceutical industry
- public and private companies
- personalized medicine
29
Future trends of pharmacogenomics in Heatlhcare practice?
Point-of-care genetic testing
- personal genomics
- population sequencing
30
Personalized medicine?
- use of individual's genetic profile
- genetic variation of enzymes that break down or activate drugs (side effects/efficacy)
- prediction of chemotherapy response
31
Interaction between DNA and Environment: drug
Epigenetic modifications which alter gene expression
32
Interaction between Environment (drug) and phenotype: drug response?
Drug exposure of sufficient quantity/duration to alter phenotype
33
Interaction between DNA and Phenotype: drug response?
Functional gene variants: coding SNP promoter variants
34
Using genetic info to enhance the therapeutic index helps by?
- identifying Non-responders
- not treating those most affected by toxicity
- adjust dose to maximize efficacy while avoiding toxicity; individualized
35
Clinical implications: Efficacy
- maximize beneficial and therapeutic repsonse
- measure of clinical effectiveness
- % of recipients who show a therapeutic response
36
Clinical Implications: Toxicity
- unwanted or harmful health effects
- % of patients who show adverse side effects at a given dose
- extreme dose responders
- non responders, drug ineffective
- adverse responders, drug causes major harmful side-effects
37
Optimal dose range?
Efficacy is greatest and toxicity is lowest
38
How do you handle non-responders?
increase dose or alternative medication
39
How do handle adverse responders?
Greatly decrease dose or an alternative form of medication
40
Describe point-of-care?
Responders treated with drug
| Nonresponders enrolled genomically guided clinical trials
41
How many genes cause exhibit an inherited phenotype?
1200 genes
| cystic fibrosis, huntington's disease
42
What disease are predisposed by certain genes?
cancer, retinoblastoma, breast cancer, polyposis colorectal cancer
43
Transcriptome? (Connecting the Genome to gene function)
- all of the expressed RNA molecules in a cell at a given time
- information about how highly various genes are expressed
- different and specific for every cell
- changes in transcriptional activity contributes to a disease
44
Proteome? (discovering the structure and function of proteins)
- shape-shifting (proteins are continually being synthesized, modified, degraded)
45
Epigenome? (new tool in studying complex diseases)
- the study of changes in the regulation of gene activity and expression that are not dependent on gene
46
How is system biology useful?
- screen can bridge the vast amount of molecular characteristics of the disease with
47
Goal of ENCODE? How do they if a gene is active?
- build a comprehensive parts list of functional elements in the human genome
- including elements that act at the protein and RNA levels, and regulatory elements
48
How many genes in a human?
20,000
49
How many chromosomes?
23
50
How many base pairs?
3 x 10^9 bp
51
Relationship between chimpanzee and human?
96% homology; 120 x 10^6 bp difference
52
Genome?
all the genetic material (DNA) of an organism
53
Genetics?
the study of single genes and its effects
| ex: cystic fibrosis, Hunting's disease
54
Genomics?
study of all the genes in the genome, including their interactions with environmental factors
ex: heart disease, asthma
55
Pharmacogenetics?
```
study of genetic influences on an individual's response to drugs
-specific gene, or group of genes to predict responses to a specific drug or class of drugs
```
56
Pharmacogenomics? (large scale study)
study of all genes collectively that influence drug responses
- genome-wide analysis
57
Genome-wide analysis?
identify genes in the search for novel drugs targets; key determinants of drug reactions
58
How many bp in the human genome?
3 billion
59
Pharmaceutical relevance of human genome?
60
What makes pharmacogenomics easy today?
- The human genome sequenced
- ADVANCES in genome seq tech
- AUTOMATIZATION significantly reduced cost in seq
- COMPUTER TECHNOLOGY; handling data
61
drug spec. trial and error?
- man drugs for certain illnesses
- not enough info about patient (so get info
- Drugs specified by trial and error (does it work, if not tweak it)
- side effects even unknown ones, serious ones
- FDA approval vis DRUG TRIALS
- drugs abandoned b/c of benefited population not convinced
62
What can help avoid drug spec. trial and error?
Genome based characterization
63
Cost of drug development?
$500 to $700 million
64
Drug development timeframe?
12 years
65
Time until patent expires?
7 years
66
What is efficacy?
% patients cured at given dose
67
What is toxicity?
% patients exhibiting side effects at a given dose
68
Therapeutic index?
Dose range at which drug shows highest efficacy and low toxicity
69
List 9 of the top 10 causes of death in the U.S. that have genetic component?
```
1 Heart disease
2 Cancer
3 Cerebrovascular disease
4 Chronic lower respiratory disease
5 (Accidents/unintentional injuries)
6 Diabetes
7 Pneumonia/influenze
8 Alzheimer's disease
9 Kidney disease
10 Septicemia
```
70
What are factors the influence drug response?
- gender
- age
- body mass
- diet
- presence of other drugs
- disease
- exposure to certain
- chemicals or toxins
- genetic factors
71
What can you do to prevent gene-environment interactions?
- screening and medical recommendations
- exposure interventions or prevention to environmental factors
- target messages and interventions aimed at changing behaviors
72
Current impact of pharmacogenomics in Healthcare practice?
- pharmaceutical industry
- public and private companies
- personalized medicine
73
Future trends of pharmacogenomics in Heatlhcare practice?
Point-of-care genetic testing
- personal genomics
- population sequencing
74
Personalized medicine?
- use of individual's genetic profile
- genetic variation of enzymes that break down or activate drugs (side effects/efficacy)
- prediction of chemotherapy response
75
Interaction between DNA and Environment: drug
Epigenetic modifications which alter gene expression
76
Interaction between Environment (drug) and phenotype: drug response?
Drug exposure of sufficient quantity/duration to alter phenotype
77
Interaction between DNA and Phenotype: drug response?
Functional gene variants: coding SNP promoter variants
78
Using genetic info to enhance the therapeutic index helps by?
- identifying Non-responders
- not treating those most affected by toxicity
- adjust dose to maximize efficacy while avoiding toxicity; individualized
79
Clinical implications: Efficacy
- maximize beneficial and therapeutic repsonse
- measure of clinical effectiveness
- % of recipients who show a therapeutic response
80
Clinical Implications: Toxicity
- unwanted or harmful health effects
- % of patients who show adverse side effects at a given dose
- extreme dose responders
- non responders, drug ineffective
- adverse responders, drug causes major harmful side-effects
81
Optimal dose range?
Efficacy is greatest and toxicity is lowest
82
How do you handle non-responders?
increase dose or alternative medication
83
How do handle adverse responders?
Greatly decrease dose or an alternative form of medication
84
Describe point-of-care?
Responders treated with drug
| Nonresponders enrolled genomically guided clinical trials
85
How many genes cause exhibit an inherited phenotype?
1200 genes
| cystic fibrosis, huntington's disease
86
What disease are predisposed by certain genes?
cancer, retinoblastoma, breast cancer, polyposis colorectal cancer
87
Transcriptome? (Connecting the Genome to gene function)
- all of the expressed RNA molecules in a cell at a given time
- information about how highly various genes are expressed
- different and specific for every cell
- changes in transcriptional activity contributes to a disease
88
Proteome? (discovering the structure and function of proteins)
- shape-shifting (proteins are continually being synthesized, modified, degraded)
89
Epigenome? (new tool in studying complex diseases)
- the study of changes in the regulation of gene activity and expression that are not dependent on gene
90
How is system biology useful?
- (personalized medicine) screen can bridge the vast amount of molecular characteristics of the disease with pharmacogenomics
- integrate patient specific data sets with drug-response profiles
91
What can one RNA do?
It has the potential to make several proteins because of splicing
92
What are the five stages following drug administration?
- absorption
- distribution
- target interaction (binding to cellular receptors or ion channels)
- metabolic processing
excretion
93
How much will genetic factors account for?
20% - 95% variation of drug response between individuals
94
What properties influence pharmacokinetics properties of drugs?
- drug metabolizing enzymes
| - drug transporters
95
What properties influence pharmacogenomics properties of drugs?
- drug targets (enzymes, receptors, ion channels)
96
What is SNP?
single nucleotide polymorphisms
97
What are sets of closely linked SNPs called?
haplotypes
98
What is a Haplotype?
- group of SNPs
- group of alleles that are rarely separated by recombination
- group of genes that was inherited together from single parent
99
What is the size of human haplotypes?
60, 000 bp
100
How many SNPs travel as a group in human haplotypes?
60 SNPs
101
Missense
- change in amino acid sequence
- about half in the coding sequence
- alter protein function
- cause of most monogenetic diseases
102
Nonsense
- change in amino acid sequence
- stop codon
- same sequence as missense
103
How many SNPs does the human genome have?
3 million, randomly
104
Which two deoxynucleotides are involved in two of three SNPs?
Cytosine to thymine
105
What region of the genome do SNPs occur?
coding and noncoding
106
What has no effect on cell function, but could predispose people to disease or influence a their drug response?
SNPs
107
What are three benefits of SNPs?
Research
Pharmaceutical products
medical diagnostics
108
True or false. Are SNPs evolutionarily stable?
True
109
What is SNP cosortium (TSC)?
A partnership of scientists and funding agencies to determine the freqency of certain SNPs in three major world populations
110
Which countries are the scientists and funding agencies from for TSC?
Canada, China, Japan, Nigeria, United Kingdom, and the U.S.
111
What does the future hold with pharmacogenetics?
testing prior to drug use (chemotherapeutics)
- selecting the optimal drug; impact on both cost and prognosis
- increasing understanding multiple genetic influences on drug action
- new technologies, reduce costs
personalized medicine
112
What's one thing that pharmacogenetics can only enhance, but never replace?
proper clinical management
113
What are several DNA-binding transcription factors?
- ATP-dependent chromatin remodeling complexes
- Histone chaperone complexes
- Histone modifying enzyme complexes
- Mediator complexes
114
What are the processes in epigenetics?
Activation and repression
115
Activated genes are?
Acetylated or methylated
116
Repressed genes are?
methylated
117
What is the difference between euchromatin and heterochromatin?
Euchromatin is lightly packed while heterochromatin is tightly packed
