What is DNA?

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(No Transcript)
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What is DNA?
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What is DNA Day?
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What is DNA Day?
April 1953 Drs. James Watson and Francis Crick
determined the structure of DNA (double helix)
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What is DNA Day?
April 2003 Human Genome Project determined the
entire DNA sequence of a human (3 billion
letters)
April 1953 Drs. James Watson and Francis Crick
determined the structure of DNA (double helix)
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What is Pharmacogenomics?
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What is Pharmacogenomics?
Pharma drug or medicine Genomics the study
of genes
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What is Pharmacogenomics?
Pharma drug or medicine Genomics the study
of genes
Personalized medicine tailored to your genes
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Case Study Breast Cancer Patients
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Case Study Breast Cancer Patients
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Case Study Breast Cancer Patients
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Case Study Breast Cancer Patients
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Helped
No Effect/Hurt
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Helped
No Effect/Hurt
Why?
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How do scientists make personalized medicine?
You
Your cells
Your DNA
Picture credit adapted from Riken Research
http//www.rikenresearch.riken.jp/eng/frontline/55
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How do scientists make personalized medicine?
You
Your cells
Its all about what makes YOUR genetic code
UNIQUE
Your DNA
Picture credit adapted from Riken Research
http//www.rikenresearch.riken.jp/eng/frontline/55
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Genetic Code DNA

• DeoxyriboNucleic Acid (DNA) contains all the
  information necessary to make a complete organism

DNA is composed of a combination of 4 nucleotides
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Genetic Code DNA

• DeoxyriboNucleic Acid (DNA) contains all the
  information necessary to make a complete organism

DNA is composed of a combination of 4 nucleotides
A
Adenine
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Genetic Code DNA

• DeoxyriboNucleic Acid (DNA) contains all the
  information necessary to make a complete organism

DNA is composed of a combination of 4 nucleotides
A
T
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Genetic Code DNA

• DeoxyriboNucleic Acid (DNA) contains all the
  information necessary to make a complete organism

DNA is composed of a combination of 4 nucleotides
A
T
C
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Genetic Code DNA

• DeoxyriboNucleic Acid (DNA) contains all the
  information necessary to make a complete organism

DNA is composed of a combination of 4 nucleotides
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The Central Dogma DNA?RNA?Protein
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The Central Dogma DNA?RNA?Protein
RNA A single-stranded copy of one gene.
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The Central Dogma DNA?RNA?Protein
RNA
Protein Proteins are composed amino acids. Amino
acids are made from triplets of nucleotides
called codons.
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The Central Dogma DNA?RNA?Protein
Codon 1
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The Central Dogma DNA?RNA?Protein
Codon 1
Codon 2
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The Central Dogma DNA?RNA?Protein
Codon 1
Codon 2
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The Central Dogma DNA?RNA?Protein
Codon 1
Codon 2
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A small change in the gene sequence can result in
a very different protein
ATG GTG CTG TCT CCT
DNA
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A small change in the gene sequence can result in
a very different protein
ATG GTG CTG TCT CCT
DNA
Met
Amino Acids/Protein
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A small change in the gene sequence can result in
a very different protein
ATG GTG CTG TCT CCT
DNA
Met
Amino Acids/Protein
Val
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A small change in the gene sequence can result in
a very different protein
ATG GTG CTG TCT CCT
DNA
Met
Leu
Amino Acids/Protein
Val
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A small change in the gene sequence can result in
a very different protein
ATG GTG CTG TCT CCT
DNA
Met
Leu
Ser
Amino Acids/Protein
Val
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A small change in the gene sequence can result in
a very different protein
ATG GTG CTG TCT CCT
DNA
Met
Leu
Ser
Pro
Amino Acids/Protein
Val
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A small change in the gene sequence can result in
a very different protein
ATG GTG CTG TCT CCT
DNA
Met
Leu
Ser
Pro
Amino Acids/Protein
Val
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A small change in the gene sequence can result in
a very different protein
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A small change in the gene sequence can result in
a very different protein
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A small change in the gene sequence can result in
a very different protein
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A small change in the gene sequence can result in
a very different protein
Words
Tom and Sam are
sad
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A small change in the gene sequence can result in
a very different protein
Words
Tom and Sam are
sad
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Variationsin our DNA make us UNIQUE!
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Helped
No Effect/Hurt
Why does Tumoricide work on some patients but not
on others?
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What are the reasons a person would react
differently to drugs?

1. Having the receptor (protein) to recognize the
   drug
2. Other physiological traits that enable you to
   respond to a drug
3. How your body processes the drugs after receiving
   it

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Drugs and Receptors
Cell
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Drugs and Receptors
Receptor (Protein)
Cell
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Drugs and Receptors
Receptor (Protein)
Cell
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Drugs and Receptors
Drug (Ligand)
Receptor (Protein)
Cell
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Drugs and Receptors
Drug (Ligand)
Receptor (Protein)
Cell
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Your DNA and Drugs

• Variation in genes can cause variation in
  receptors

Cell
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Your DNA and Drugs

• Variation in genes can cause variation in
  receptors

Cell
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Your DNA and Drugs

• Variation in genes can cause variation in
  receptors

Cell
Cell
Cell
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Your DNA and Drugs

• Variation in genes can cause variation in
  receptors

Cell
Cell
Cell
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Your DNA and Drugs

• Variation in genes can cause variation in
  receptors

Too Many (hypersensitive)
Cell
Cell
Cell
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Your DNA and Drugs

• Variation in genes can cause variation in
  receptors

Too Many (hypersensitive)
Too Few (hyposensitive)
Cell
Cell
Cell
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Your DNA and Drugs

• Variation in genes can cause variation in
  receptors

Too Many (hypersensitive)
Too Few (hyposensitive)
Mutated (insensitive)
Cell
Cell
Cell
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Where Drugs Fit In
Lock Receptor
Key Drug
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Lets do a class case study!
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Lets do a class case study!

• Taste the PTC strip
• (This wont hurt you - not a toxic chemical)
• What do you taste?

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Lets do a class case study!

• Taste the PTC strip
• (This wont hurt you - not a toxic chemical)
• What do you taste?

Why does the strip taste bitter to some and have
no taste for others? What is your hypothesis?
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Why can some people taste PTC and others cant?
PTC-Receptor
Taste cell
This tastes bitter!
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Why can some people taste PTC and others cant?
Non-binding PTC-Receptor
PTC-Receptor
Taste cell
Taste cell
This tastes bitter!
I dont taste anything!
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Where does tasting PTC come from?
You have two copies of every gene one from Mom
and one from Dad
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Where does tasting PTC come from?
You have two copies of every gene one from Mom
and one from Dad
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Where does tasting PTC come from?
You have two copies of every gene one from Mom
and one from Dad
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Where does tasting PTC come from?
You have two copies of every gene one from Mom
and one from Dad

• Your two genes are the genotype

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Where does tasting PTC come from?
You have two copies of every gene one from Mom
and one from Dad

• Your two genes are the genotype
• A gene can be dominant or recessive

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Where does tasting PTC come from?
You have two copies of every gene one from Mom
and one from Dad

• Your two genes are the genotype
• A gene can be dominant or recessive
• The expressed trait is a phenotype

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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
For individuals with these genotypes, what would
their phenotypes be?
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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
This tastes REALLY bitter!
SUPERTASTER
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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
Tt
tt
This tastes REALLY bitter!
This tastes bitter!
TASTER
SUPERTASTER
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Tasting PTC is dominant (T) over inability taste
PTC which is recessive (t)
Tt
tt
I dont taste anything!
This tastes REALLY bitter!
This tastes bitter!
TASTER
NON-TASTER
SUPERTASTER
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Drug receptor summary
PTC

• Ability to taste PTC has a very strong genetic
  component
• PTC chemical and Drugs chemical
• Differences in ability to taste PTC is similar to
  differences in reactions to drugs

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Helped
No Effect/Hurt
Why?
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Two Types of Breast Cancer
Y
Y
Y
Her2-
Her2

• Tumoricide is a personalized medication
• Tumoricide only works for Her2 breast tumors

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Helped
No Effect/Hurt
Her2
Her2-
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Screening for Her2 Cells
American Journal of Clinical Pathology.
2008129(2)263-273
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Screening for Her2 Cells
?

American Journal of Clinical Pathology.
2008129(2)263-273
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Screening for Her2 Cells
?

American Journal of Clinical Pathology.
2008129(2)263-273
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Breast Cancer

• 1990
• Surgery
• Radiation
• Chemotherapy (drugs)

• 2012
• Surgery
• Radiation
• Chemotherapy
• Specialized treatments (for certain types of
  breast cancer)

http//www.ucdmc.ucdavis.edu/welcome/features/2008
0709_cancer_sweeney/index.html
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What are the reasons a person would react
differently to drugs?

1. Having the receptor (protein) to recognize the
   drug
2. Other physiological traits that enable you to
   respond to a drug
3. How your body processes the drugs after receiving
   it

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The presence of receptors influence how we react
to drugs like Tumoricide or chemicals like PTC
Y
Y
Y
Her2-
Her2
Tumoricide Does Not Work
Tumoricide Works!
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The presence of receptors influence how we react
to drugs like Tumoricide or chemicals like PTC
This tastes REALLY bitter!
I dont taste anything!
This tastes bitter!
SUPERTASTER
TASTER
NON-TASTER
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Where are the PTC receptors?
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Where are the PTC receptors?
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What are taste buds?
Taste buds are found on papillae on your tongue
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What are taste buds?
Taste buds are found on papillae on your tongue
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What are taste buds?
Taste buds are found on papillae on your tongue
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What are taste buds?
Taste buds are found on papillae on your tongue
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What are taste buds?
Taste buds are found on papillae on your tongue
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What are taste buds?
Taste buds are found on papillae on your tongue
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Question
Are there other traits that can allow a person to
more strongly taste PTC?
Hypothesis
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Question
Are there other traits that can allow a person to
more strongly taste PTC?
Hypothesis

• If a person has more taste buds, then he/she may
  be able to taste the PTC more strongly.

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Lets test our hypothesis and count our taste
buds!

1. Lollipop time! Lick your lollipop such that the
   blue gets all over your tongueespecially the tip
   of your tongue.
2. Once your tongue is really blue, place one hole
   reinforcer on the tip of your tongueso it looks
   like the picture on the bottom on this slide.
3. Have your partner count the bumps or papillae on
   your tonguethese will not stain blue.

Remember that your taste buds are on your
papillae. Therefore the number of papillae
correlates to the amount of taste buds on your
tongue.
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Counting the number of tongue papillae
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Counting the number of tongue papillae
5 papillae
20 papillae
35 papillae
Come to the front of the class to report your PTC
phenotype (taster, super-taster and non-taster)
and the number of papillae on your tongue
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Please PAUSE and take a moment to count your
taste buds and report your results on the
spreadsheet at the front of the classroom
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Ideal graph representing the number of tongue
papillae related to the phenotype of PTC taste
These results support our hypothesis that the
super-taster has more papillae!
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Ideal graph representing the number of tongue
papillae related to the phenotype of PTC taste
The number of papillae in the non-taster is
variable. Why would the number of papillae be
variable in a non-taster?
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Please PAUSE and discuss why you think being a
PTC non-taster does not correlate with number of
taste buds.
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What does it take to be a PTC Taster?
Two traits are important for determining PTC
taste sensitivity
1) PTC receptor genotypeDo you have the
receptors that enable you to taste PTC
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What does it take to be a PTC Taster?
Two traits are important for determining PTC
taste sensitivity
1) PTC receptor genotypeDo you have the
receptors that enable you to taste PTC
2) The density of papillae on your tongue
correlates to the sensitivity of tasting PTC
taster
super-taster
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What are the reasons a person would react
differently to drugs?

1. Having the receptor (protein) to recognize the
   drug
2. Other physiological traits that enable you to
   respond to a drug
3. How your body processes the drugs after receiving
   it

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A Drugs Life

• ADME
• Absorption
• Distribution
• Metabolism
• Excretion

http//publications.nigms.nih.gov/medbydesign/chap
ter1.html
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Metabolic enzymes
Enzymes
Metabolites
Drug
Liver
DNA variations in special proteins in the liver
called enzymes can influence a persons ability
to metabolize certain drugs
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Adverse Drug Reactions (ADR)

• Definition- unwanted, negative response to a
  prescribed drug at normal doses and during normal
  use
• Examples?

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Adverse Drug Reactions (ADR)

• Definition- unwanted, negative response to a
  prescribed drug at normal doses and during normal
  use
• Examples?
• There are multiple causes for ADRs
• environmental basis
• genetic basis

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Adverse Drug Reactions (ADR)

• Definition- unwanted, negative response to a
  prescribed drug at normal doses and during normal
  use
• Examples?
• There are multiple causes for ADRs
• environmental basis
• genetic basis
• Poor metabolizers can experience ADRs at normally
  therapeutic drug doses

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Case study Nortriptyline metabolism

• Three women of the same height, weight, age,
  and racial background are depressed and go to the
  doctor.
• The doctor prescribes an antidepressant,
  Nortriptyline, at a dose of 100 mg.

• Person A has an adverse reaction
• Person B nothing happens
• Person C gets better

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Case study Nortriptyline metabolism

• Three women of the same height, weight, age,
  and racial background are depressed and go to the
  doctor.
• The doctor prescribes an antidepressant,
  Nortriptyline, at a dose of 100 mg.

• Person A has an adverse reaction
• Person B nothing happens
• Person C gets better

Why?
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ADME of Nortriptyline
100mg Nortriptyline
Adverse reaction
Nothing happens
Gets better
How much active drug in blood?
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ADME of Nortriptyline
100mg Nortriptyline
Adverse reaction
Nothing happens
Gets better
95mg
5mg
50mg
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DNA variation influence drug metabolism
Enzymes
Metabolites
Drug
Liver
Poor Metabolizer
95mg
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DNA variation influence drug metabolism
Enzymes
Metabolites
Drug
Liver
Ultrarapid Metabolizer
5mg
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DNA variation influence drug metabolism
Enzymes
Metabolites
Drug
Liver
Intermediate Metabolizer
50mg
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2012 - What do doctors do?
Poor Metabolizer
Ultrarapid Metabolizer
Decrease Dose
Increase Dose
Or change drug
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Today One-size-fits-all drugs

• Current drug development system develops drugs
  for the average patient
• No simple way to determine who will respond well
  and who will respond poorly
• One size does NOT fit all!
• Whats the solution?

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Today One-size-fits-all drugs

• Current drug development system develops drugs
  for the average patient
• No simple way to determine who will respond well
  and who will respond poorly
• One size does NOT fit all!
• Whats the solution?

Pharmacogenomics (PGx) Personalized Medicine
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April, 2050

• You wake up feeling terrible, and you know it's
  time to see a doctor. In the office, the
  physician looks you over, listens to your
  symptoms, and decides to prescribe you a drug.
• But first, the doctor takes a look at your DNA.
• TODAY vs. FUTURE
• Today Drugs are One-Size-Fits-All
• Future Drugs Specific for You!
• More effective minimizes side effects

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Summary
Genetic variation leads to phenotypic differences
and differences in how we all react to drugs.
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Summary

• Genetic variation leads to phenotypic differences
  and differences in how we all react to drugs.
• Having the receptor (protein) to recognize the
  drug
• PTC and HER2 receptors

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Summary

• Genetic variation leads to phenotypic differences
  and differences in how we all react to drugs.
• Having the receptor (protein) to recognize the
  drug
• PTC and HER2 receptors
• 2. Other physiological traits that enable you to
  respond to a drug
• Number of taste buds on tongue

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Summary

• Genetic variation leads to phenotypic differences
  and differences in how we all react to drugs.
• Having the receptor (protein) to recognize the
  drug
• PTC and HER2 receptors
• 2. Other physiological traits that enable you to
  respond to a drug
• Number of taste buds on tongue
• 3. How drugs are processed in the body
• Enzymes in liver metabolize drugs

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Pharamcogenomics Using peoples genetic
information for the right drug at the right dose
at the right time!
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About the Scientist

• What do I study?
• Why do I love science?
• Questions?

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Join us for the 1st annual NC DNA Day science
festival to learn more about the biological and
biomedical research going on in the state!
May 18, 2013 UNC Student Union Great Hall
10am-12pm
Register to attend The classroom with the most
attendees will win a pizza party!
Science Art Contest Create a painting, drawing or
3D model that embodies biomedical sciences.
Prizes will be awarded! See website for more
info.
ncdnaday.org/festival
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REGISTER FOR THE FIRST ANNUAL DNA DAY 5K!

• Run to Support Science Outreach and Education in
  NC
• 900 AM Saturday, May 18th 2013
• Run Through UNC Chapel Hill Campus
• ncdnaday.org/5K