What is DNA?. What is DNA? What is DNA Day? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double.

What is DNA?

What is DNA Day?

What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

What is DNA Day? April 1953 April 2003
Drs. James Watson and Francis Crick determined the structure of DNA (double helix) April 2003 Human Genome Project determined the entire DNA sequence of a human (3 billion letters)

What is Pharmacogenomics?
** Powerpoint drawn graphics R X

Pharma = drug or medicine Genomics = the study of genes ** Powerpoint drawn graphics R X

Pharma = drug or medicine Genomics = the study of genes Personalized medicine tailored to your genes ** Powerpoint drawn graphics R X

Case Study – Breast Cancer Patients
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Tumoricide ** Powerpoint drawn graphics

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30% ** Powerpoint drawn graphics

No Effect/Hurt Helped Tumoricide ** Powerpoint drawn graphics

No Effect/Hurt Helped Tumoricide Why? ** Powerpoint drawn graphics

How do scientists make personalized medicine?
You Your cells Your DNA Picture credit: adapted from Riken Research:

It’s all about what makes YOUR genetic code UNIQUE
How do scientists make personalized medicine? You Your cells It’s all about what makes YOUR genetic code UNIQUE Your DNA Picture credit: adapted from Riken Research:

DNA is composed of a combination of 4 nucleotides
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

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

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 Adenine Thymine

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 Adenine Thymine Cytosine

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 G Adenine Thymine Cytosine Guanine

The Central Dogma: DNARNAProtein
DNA: A long double-stranded string of nucleotides that encode for many genes. Gene

DNA: A long double-stranded string of nucleotides that encode for many genes. Gene RNA: A single-stranded copy of one gene. RNA

DNA: A long double-stranded string of nucleotides that encode for many genes. Gene RNA: A single-stranded copy of one gene. RNA Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons.

DNA: A long double-stranded string of nucleotides that encode for many genes. Gene RNA: A single-stranded copy of one gene. Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons. Codon 1

DNA: A long double-stranded string of nucleotides that encode for many genes. Gene RNA: A single-stranded copy of one gene. Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons. Codon 1 Codon 2

DNA: A long double-stranded string of nucleotides that encode for many genes. Gene RNA: A single-stranded copy of one gene. Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons. Amino acid 1 Amino acid 2 Codon 1 Codon 2

DNA: A long double-stranded string of nucleotides that encode for many genes. Gene RNA: A single-stranded copy of one gene. Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons. Amino acid 1 Amino acid 2 Protein! Codon 1 Codon 2

A small change in the gene sequence can result in a very different protein
DNA: ATG GTG CTG TCT CCT SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 29 29

DNA: ATG GTG CTG TCT CCT Amino Acids/Protein: Met SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 30 30

DNA: ATG GTG CTG TCT CCT Amino Acids/Protein: Met Val SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 31 31

DNA: ATG GTG CTG TCT CCT Amino Acids/Protein: Met Val Leu SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 32 32

DNA: ATG GTG CTG TCT CCT Amino Acids/Protein: Met Val Leu Ser SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 33 33

DNA: ATG GTG CTG TCT CCT Amino Acids/Protein: Met Val Leu Ser Pro SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 34 34

DNA: ATG GTG CTG TCT CCT Amino Acids/Protein: Met Val Leu Ser Pro SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 35 35

ATG GTG CTG TCT CCT Met Leu Ser Pro DNA: Amino Acids/Protein: Val ATG GTG CTG TCT ACT DNA: SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 36 36

ATG GTG CTG TCT CCT Met Leu Ser Pro DNA: Amino Acids/Protein: Val ATG GTG CTG TCT ACT Met Leu Ser Thr DNA: Amino Acids/Protein: Val SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 37 37

ATG GTG CTG TCT CCT Met Leu Ser Pro DNA: Amino Acids/Protein: Val Words: Tom and Sam are bad ATG GTG CTG TCT ACT Met Leu Ser Thr DNA: Amino Acids/Protein: Val SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. 38 38

ATG GTG CTG TCT CCT Met Leu Ser Pro DNA: Amino Acids/Protein: Val Words: Tom and Sam are bad ATG GTG CTG TCT ACT Met Leu Ser Thr DNA: Amino Acids/Protein: Val SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. Words: Tom and Sam are sad 39 39

Changes in DNA are called variations or mutations
A small change in the gene sequence can result in a very different protein ATG GTG CTG TCT CCT Met Leu Ser Pro DNA: Amino Acids/Protein: Val Words: Tom and Sam are bad ATG GTG CTG TCT ACT Met Leu Ser Thr DNA: Amino Acids/Protein: Val SLIDE 11: How does an Altered Gene Result in an Altered Protein? Each 3-letter codon is translated into an amino acid. Example: SAM AND TOM ATE THE HAM – if we change A to I, does not make sense. If we change one letter in DNA, can change one letter in amino acid, and protein may not work properly Changes in DNA are called mutations. There are many types of mutations. Words: Tom and Sam are sad Changes in DNA are called variations or mutations Variations in the DNA (genotype) can cause observable changes (phenotype) in individuals 40 40

Variations in our DNA make us UNIQUE!

Why does Tumoricide work on some patients but not on others?
No Effect/Hurt Helped Tumoricide ** Powerpoint drawn graphics Why does Tumoricide work on some patients but not on others?

What are the reasons a person would react differently to drugs?
Having the receptor (protein) to recognize the drug Other physiological traits that enable you to respond to a drug How your body processes the drugs after receiving it So what does all this DNA stuff have to do with medicine? Well we are going to look at a few genetic reasons why different people may have different reactions to the same drug, like the Tumoricide story Sarah told you all about. The first way people react differently is the receptor proteins they have to recognize drugs.

Drugs and Receptors Cell
Our cells have all the DNA in them to make all the different kinds of proteins they need. **Powerpoint drawn graphics. Cell

Drugs and Receptors Cell Receptor (Protein)
This includes receptor proteins. Receptors are proteins that sit on the outside of our cells and receive signals from the external environment. **Powerpoint drawn graphics. Cell

Drugs and Receptors Cell Receptor (Protein)
Sometimes, these signals are drugs! Molecules that bind to proteins are also called ligands. Drugs are ligands that bind to a specific type of receptor. **Powerpoint drawn graphics. Cell

Drugs and Receptors Cell Drug (Ligand) Receptor (Protein)
Sometimes, these signals are drugs! Molecules that bind to proteins are also called ligands. Drugs are ligands that bind to a specific type of receptor. **Powerpoint drawn graphics. Cell

Drugs and Receptors Cell Drug (Ligand) Receptor (Protein)
When the cells receives the signal, this gives a therapeutic effect by blocking other molecules from binding to the receptor or telling the cell to do something different that makes us feel better. **Powerpoint drawn graphics. Cell

Variation in genes can cause variation in receptors
Your DNA and Drugs Variation in genes can cause variation in receptors But, still, what does that have to do with your DNA? Since DNA gives the code for proteins, changes in your genes can cause changes to your receptors. **Powerpoint drawn graphics. Cell

Your DNA and Drugs Variation in genes can cause variation in receptors For example mutations in DNA can cause the cells to make more receptors than average, so the cell has more to bind to **Powerpoint drawn graphics. Cell

Your DNA and Drugs Variation in genes can cause variation in receptors Cell Or a mutation may cause the cell to make less receptors, so the drug doesn’t have as many to bind to. These variations in our genes can cause variations in how we respond to drugs **Powerpoint drawn graphics. Cell Cell

Your DNA and Drugs Variation in genes can cause variation in receptors Cell Cell And sometimes mutations cause a change in the receptor itself, which makes it unable to bind with the drug. **Powerpoint drawn graphics. Cell Cell

Your DNA and Drugs Variation in genes can cause variation in receptors Too Many (hypersensitive) Cell Cell With too many receptors the cell may receive more signals and amlify the drug effect. Overreaction to a drug is called hypersensitivity. **Powerpoint drawn graphics. Cell Cell

Your DNA and Drugs Variation in genes can cause variation in receptors Too Many (hypersensitive) Too Few (hyposensitive) Cell Cell With too few receptors and the drug may not find enough to bind to and the drugs effect will be small. Under reaction to a drug is called hyposensitivity. **Powerpoint drawn graphics. Cell Cell

Your DNA and Drugs Variation in genes can cause variation in receptors Too Many (hypersensitive) Too Few (hyposensitive) Mutated (insensitive) Cell Cell Or a Mutated receptor may not be able to bind the drug at all, so the cell sees no effect. When a patient sees no reaction to a drug it is called insensitivity. **Powerpoint drawn graphics. Cell Cell

Where Drugs “Fit” In Lock = Receptor Key = Drug
But how does a drug know where to bind? Drugs are designed to fit into specific receptors on our cells, just like a key is designed to fit into a specific lock. **Powerpoint drawn graphics and clipart. Lock = Receptor Key = Drug

Let’s do a class case study!
Now that we have learned a bit about our bodies reactions to drugs, lets do an in-class “personalized medicine” case study to test our genetic variation. You all have PTC strips, pick it up and place it on your tounge for five seconds to taste it. Don’t just lick it, but leave it on there for a bit to see if you can taste anything. Don’t worry- PTC is a non-toxic chemical, so tasting it won’t hurt you! What do you taste? Write down what you tasted and compare it with your classmates. PAUSE POINT.

Taste the PTC strip (This won’t hurt you - not a toxic chemical) What do you taste? Now that we have learned a bit about our bodies reactions to drugs, lets do an in-class “personalized medicine” case study to test our genetic variation. You all have PTC strips, pick it up and place it on your tounge for five seconds to taste it. Don’t just lick it, but leave it on there for a bit to see if you can taste anything. Don’t worry- PTC is a non-toxic chemical, so tasting it won’t hurt you! What do you taste? Write down what you tasted and compare it with your classmates. PAUSE POINT.

Taste the PTC strip (This won’t 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? Did it taste yucky to some of you and just like plain paper to others? Why do you think that is? Do you think it could have anything to do with your genetics? Discuss your hypothesis with your classmates. PAUSE POINT.

Why can some people taste PTC and others can’t?
PTC-Receptor PTC Taste cell Another genetic variant of the PTC receptor cannot bind PTC- so the strip doesn’t taste like anything. This key does not fit into the lock! How does this happen? **Powerpoint drawn graphics “This tastes bitter!”

“I don’t taste anything!”
Why can some people taste PTC and others can’t? Non-binding PTC-Receptor PTC-Receptor PTC PTC Taste cell Another genetic variant of the PTC receptor cannot bind PTC- so the strip doesn’t taste like anything. This key does not fit into the lock! How does this happen? **Powerpoint drawn graphics Taste cell “This tastes bitter!” “I don’t taste anything!”

Where does tasting PTC come from?
You have two copies of every gene: one from Mom and one from Dad Remember how Jessica told you that we get one copy of each gene from each of our parents? Well, lets review. **Clip art

You have two copies of every gene: one from Mom and one from Dad Your two genes are the genotype The two genes you get from mom and dad are known as a genotype. **Clip art

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 But genes can be dominant or recessive. When a dominant gene is present it’s trait will overcome the recessive gene. **Clip art

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 This determines which trait is seen, which is a person’s phenotype. So, Tasting PTC comes from our genes! **Clip art

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)
We each have two copies of the PTC receptor gene- one from our Mom, and one from our Dad The gene for tasting PTC is dominant over the gene for not tasting PTC which is recessive. Lets look at an example of three people that taste PTC differently. ** Powepoint drawn graphics

The person on the left has two copies of the dominant gene for tasting PTC, so all of their receptors will be good at binding it. ** Powepoint drawn graphics

The person in the middle has one dominant PTC tasting gene and one recessive non-tasting gene, so some of their receptors will be good at binding PTC while others wont. ** Powepoint drawn graphics

And the person on the right has two copies of the recessive non-tasting PTC gene, so all of there receptors will be unable to bind PTC. ** Powepoint drawn graphics

For individuals with these genotypes, what would their phenotypes be?
Tasting PTC is dominant (T) over inability taste PTC which is recessive (t) Tt tt TT And the person on the right has two copies of the recessive non-tasting PTC gene, so all of there receptors will be unable to bind PTC. ** Powepoint drawn graphics For individuals with these genotypes, what would their phenotypes be?

“This tastes REALLY bitter!”
Tasting PTC is dominant (T) over inability taste PTC which is recessive (t) Tt tt TT The double dominant bigT bigT genotype gives a SUPERTASTER phenotype, which tastes the bitterness of PTC very strongly as soon as it touches their tounge. ** Powepoint drawn graphics “This tastes REALLY bitter!” SUPERTASTER

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t) TT Tt tt The bigT little T genotype yields a TASTER phenotype that may have had to keep the strip on their tongue for awhile, but it still tasted bitter eventually. ** Powepoint drawn graphics “This tastes REALLY bitter!” “This tastes bitter!” SUPERTASTER TASTER

The double recessive genotype, little T little T, gives a NON-TASTER phenotype that never tastes anything on the strip. Which person were you? Where you a supertaster that tasted the bitterness right away? Did it taste a little bitter after a while? Or did you just taste paper? Write down your phenotype, we are going to use it later in our data analysis. ** Powepoint drawn graphics “This tastes REALLY bitter!” “This tastes bitter!” “I dont taste anything!” SUPERTASTER TASTER NON-TASTER

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 But how is our experiment related to personalized medicine? As we have learned, the Ability to taste PTC has a very strong genetic component. PTC is a chemical and Drugs are also chemicals. You have just performed a genetic test for your reaction to a chemical! Ad the differences in how your class tasted PTC is very similar to the difference in patients reactions to drugs ** ChemDraw created graphics

No Effect/Hurt Helped Tumoricide Why? ** Powepoint drawn graphics

Two Types of Breast Cancer
Her2- Her2+ ** Powepoint drawn graphics Tumoricide is a personalized medication Tumoricide only works for Her2+ breast tumors

No Effect/Hurt Helped Her2+ Her2- Tumoricide
** Powepoint drawn graphics

Screening for Her2+ Cells
**American Journal of Clinical Pathology. 2008;129(2): American Journal of Clinical Pathology. 2008;129(2):

Tumoricide = ? + YES! This patient is Her2+ and should be treated with Tumoricide ** Powepoint drawn graphics American Journal of Clinical Pathology. 2008;129(2):

Tumoricide = ✓ + YES! This patient is Her2+ and should be treated with Tumoricide ** Powepoint drawn graphics American Journal of Clinical Pathology. 2008;129(2):

Breast Cancer 1990 2012 Surgery Radiation Chemotherapy (drugs) Surgery
Specialized treatments (for certain types of breast cancer) **

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

Tumoricide Does Not Work
The presence of receptors influence how we react to drugs like Tumoricide or chemicals like PTC Y Y Y Her2- Her2+ The double recessive genotype, little T little T, gives a NON-TASTER phenotype that never tastes anything on the strip. Which person were you? Where you a supertaster that tasted the bitterness right away? Did it taste a little bitter after a while? Or did you just taste paper? Write down your phenotype, we are going to use it later in our data analysis. ** Powepoint drawn graphics Tumoricide Does Not Work Tumoricide Works!

The presence of receptors influence how we react to drugs like Tumoricide or chemicals like PTC TT Tt tt The double recessive genotype, little T little T, gives a NON-TASTER phenotype that never tastes anything on the strip. Which person were you? Where you a supertaster that tasted the bitterness right away? Did it taste a little bitter after a while? Or did you just taste paper? Write down your phenotype, we are going to use it later in our data analysis. ** Powepoint drawn graphics “This tastes REALLY bitter!” “This tastes bitter!” “I dont taste anything!” SUPERTASTER TASTER NON-TASTER

Where are the PTC receptors?
Let’s look at the tongue’s anatomy The receptors and cells for mammalian taste Jayaram Chandrashekar, Mark A. Hoon, Nicholas J. P. Ryba & Charles S. ZukerNature 444, (16 November 2006) Taste buds are composed of TRCs (depending on the species), distributed across different papillae. Circumvallate papillae are found at the very back of the tongue and contains thousands (human) of taste buds. Foliate papillae are present at the posterior lateral edge of the tongue and contain a dozen to hundreds of taste buds. Fungiform papillae contain one or a few taste buds and are found in the anterior two-thirds of the tongue. TRCs project microvillae to the apical surface of the taste bud, where they form the 'taste pore'; this is the site of interaction with tastants. b, Recent molecular and functional data have revealed that, contrary to popular belief, there is no tongue 'map': responsiveness to the five basic modalities ﾑ bitter, sour, sweet, salty and umami is present in all areas of the tongue

Where are the PTC receptors?
They are on your taste buds! Yummy! Let’s look at the tongue’s anatomy The receptors and cells for mammalian taste Jayaram Chandrashekar, Mark A. Hoon, Nicholas J. P. Ryba & Charles S. ZukerNature 444, (16 November 2006) Taste buds are composed of TRCs (depending on the species), distributed across different papillae. Circumvallate papillae are found at the very back of the tongue and contains thousands (human) of taste buds. Foliate papillae are present at the posterior lateral edge of the tongue and contain a dozen to hundreds of taste buds. Fungiform papillae contain one or a few taste buds and are found in the anterior two-thirds of the tongue. TRCs project microvillae to the apical surface of the taste bud, where they form the 'taste pore'; this is the site of interaction with tastants. b, Recent molecular and functional data have revealed that, contrary to popular belief, there is no tongue 'map': responsiveness to the five basic modalities ﾑ bitter, sour, sweet, salty and umami is present in all areas of the tongue

Taste buds are found on papillae on your tongue
What are taste buds? Taste buds are found on papillae on your tongue

Taste buds are found on papillae on your tongue
What are taste buds? Taste buds are found on papillae on your tongue Papillae bumps on your tongue

What are taste buds? Taste buds are found on papillae on your tongue
bumps on your tongue Taste buds cells are found on the papilla

PTC receptors are found on the taste buds Papillae bumps on your tongue Taste buds cells are found on the papilla

PTC receptors are found on the taste buds Nerve Cell Transmits signal to brain Papillae bumps on your tongue Taste buds cells are found on the papilla

Brain Wow! This tastes really bitter PTC receptors are found on the taste buds Nerve Cell Transmits signal to brain Papillae bumps on your tongue Taste buds cells are found on the papilla

Question: Hypothesis:
Are there other traits that can allow a person to more strongly taste PTC? Hypothesis: In addition to the genes that the students inherit, (** Don’t forget about the genes!**) Ask them whether they think tasting PTC will correlate with MORE or FEWER fungiform papillae

Question: Hypothesis:
Are there other traits that can allow a person to more strongly taste PTC? Hypothesis: In addition to the genes that the students inherit, (** Don’t forget about the genes!**) Ask them whether they think tasting PTC will correlate with MORE or FEWER fungiform papillae If a person has more taste buds, then he/she may be able to taste the PTC more strongly.

Let’s test our hypothesis and count our taste buds!
Lollipop time! Lick your lollipop such that the blue gets all over your tongue…especially the tip of your tongue. Once your tongue is really blue, place one hole reinforcer on the tip of your tongue—so it looks like the picture on the bottom on this slide. Have your partner count the bumps or papillae on your tongue…these 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. *

Counting the number of tongue papillae

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

Please PAUSE and take a moment to count your taste buds and report your results on the spreadsheet at the front of the classroom

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!

The number of papillae in the non-taster is variable.
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?

Please PAUSE and discuss why you think being a PTC non-taster does not correlate with number of taste buds.

What does it take to be a PTC Taster?
Two traits are important for determining PTC taste sensitivity 1) PTC receptor genotype—Do you have the receptors that enable you to taste PTC

What does it take to be a PTC Taster?
Two traits are important for determining PTC taste sensitivity 1) PTC receptor genotype—Do 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 super-taster taster

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

A Drug’s Life ADME Absorption Distribution Metabolism Excretion
Scientists have names for the four basic stages of a medicine's life in the body: absorption, distribution, metabolism, and excretion or ADME. Medicines can be absorbed into the body in many different ways. Can anyone give me an example of how a drug enters the body? [A few of the most common ways to administer drugs are oral (swallowing an aspirin tablet), inhalation (like an asthma medications), intramuscular (getting a flu shot in an arm muscle), subcutaneous (injecting insulin just under the skin), intravenous (receiving chemotherapy through a vein), or transdermal (wearing a skin patch).] After that the drug is absorbed into the blood stream it is distributed throughout the body to the targeted organ. Then it is broken down, or metabolized. This usually occurs in the body’s chemical processing and detoxifying plant – The liver – where chemicals are cut apart, stuck together, or transformed, making the substance easier to get rid of or excreted. There are many proteins involved in each of these processes. You can imagine if a person had a genetic variation in a gene that affects one of these proteins then there may be a roadblock in the ADME process and a drug might not work the way it was intended.

Metabolic enzymes Enzymes Drug Metabolites
Liver DNA variations in special proteins in the liver called enzymes can influence a person’s ability to metabolize certain drugs

Adverse Drug Reactions (ADR)
Definition- unwanted, negative response to a prescribed drug at normal doses and during normal use Examples?

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

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

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

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. B Person A has an adverse reaction Person B nothing happens Person C gets better… A C Why?

ADME of Nortriptyline 100mg Nortriptyline A B C Adverse reaction
Nothing happens Gets better How much active drug in blood?

ADME of Nortriptyline 95mg 5mg 50mg 100mg Nortriptyline A B C
Adverse reaction Nothing happens Gets better 95mg 5mg 50mg

DNA variation influence drug metabolism
Enzymes Drug Metabolites Liver Poor Metabolizer 95mg

DNA variation influence drug metabolism
Enzymes Drug Metabolites Liver Ultrarapid Metabolizer 5mg

DNA variation influence drug metabolism Intermediate Metabolizer
Enzymes Drug Metabolites Liver Intermediate Metabolizer 50mg

2012 - What do doctors do? Or change drug A B C Poor Metabolizer
Ultrarapid Metabolizer Decrease Dose Increase Dose Or change drug

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! What’s the solution?

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! What’s the solution? Pharmacogenomics (PGx) Personalized Medicine

Future = Drugs Specific for You!
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

Summary Genetic variation leads to phenotypic differences and differences in how we all react to drugs. Having the receptor (protein) to recognize the drug Other physiological traits that enable you to respond to a drug How your body processes the drugs after receiving it Number of the proteins that recognize the drug (receptors) What are the reasons a person would react differently to drugs?

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 Having the receptor (protein) to recognize the drug Other physiological traits that enable you to respond to a drug How your body processes the drugs after receiving it Number of the proteins that recognize the drug (receptors) What are the reasons a person would react differently to drugs?

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 Having the receptor (protein) to recognize the drug Other physiological traits that enable you to respond to a drug How your body processes the drugs after receiving it Number of the proteins that recognize the drug (receptors) What are the reasons a person would react differently to drugs?

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 Having the receptor (protein) to recognize the drug Other physiological traits that enable you to respond to a drug How your body processes the drugs after receiving it Number of the proteins that recognize the drug (receptors) What are the reasons a person would react differently to drugs?

Pharamcogenomics Using people’s genetic information for the right drug at the right dose at the right time! R X

What is DNA?. What is DNA? What is DNA Day? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double.

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Presentation on theme: "What is DNA?. What is DNA? What is DNA Day? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double."— Presentation transcript:

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What is DNA?. What is DNA? What is DNA Day? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double.

Similar presentations

Presentation on theme: "What is DNA?. What is DNA? What is DNA Day? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double."— Presentation transcript:

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About project

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