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

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Page 1: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)
Page 2: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

What is DNA?

Page 3: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

What is DNA Day?

Page 4: What is DNA? 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

Drs. James Watson and Francis Crick

determined the structure of DNA

(double helix)

Page 5: What is DNA? What is DNA Day? April 1953 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 DNA Day?

April 1953

Drs. James Watson and Francis Crick

determined the structure of DNA

(double helix)

Page 6: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

What is Pharmacogenomics?

RX

Page 7: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Pharma = drug or medicine Genomics = the study of genes

RX

What is Pharmacogenomics?

Page 8: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Personalized medicine tailored to your genes

Pharma = drug or medicine Genomics = the study of genes

RX

What is Pharmacogenomics?

Page 9: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Case Study – Breast Cancer Patients

Page 10: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Case Study – Breast Cancer Patients

Tumoricide

Page 11: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Case Study – Breast Cancer Patients

Page 12: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Case Study – Breast Cancer Patients

30%

Page 13: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

HelpedNo Effect/Hurt

Tumoricide

Page 14: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

HelpedNo Effect/Hurt

Tumoricide

Why?

Page 15: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

You Your cells

Your DNA

Picture credit: adapted from Riken Research: http://www.rikenresearch.riken.jp/eng/frontline/5514

How do scientists make personalized medicine?

Page 16: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

You Your cells

Your DNA

Picture credit: adapted from Riken Research: http://www.rikenresearch.riken.jp/eng/frontline/5514

How do scientists make personalized medicine?

It’s all about what makes YOUR genetic code UNIQUE

Page 17: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Genetic Code: DNADeoxyriboNucleic Acid (DNA) contains all the information

necessary to make a complete organism

DNA is composed of a combination of 4 nucleotides

Page 18: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Genetic Code: DNADeoxyriboNucleic Acid (DNA) contains all the information

necessary to make a complete organism

DNA is composed of a combination of 4 nucleotides

A

Adenine

Page 19: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Genetic Code: DNADeoxyriboNucleic 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

Page 20: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Genetic Code: DNADeoxyriboNucleic 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

Page 21: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Genetic Code: DNADeoxyriboNucleic 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

Page 22: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA: A long double-stranded string of nucleotides that encode for many genes.

Gene

The Central Dogma: DNARNAProtein

Page 23: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA: A long double-stranded string of nucleotides that encode for many genes.

Gene

RNA: A single-stranded copy of one gene.

RNA

The Central Dogma: DNARNAProtein

Page 24: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA: A long double-stranded string of nucleotides that encode for many genes.

Gene

RNA: A single-stranded copy of one gene.

The Central Dogma: DNARNAProtein

RNA

Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons.

Page 25: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA: A long double-stranded string of nucleotides that encode for many genes.

Gene

Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons.

RNA: A single-stranded copy of one gene.

The Central Dogma: DNARNAProtein

Codon 1

Page 26: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA: A long double-stranded string of nucleotides that encode for many genes.

Gene

Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons.

RNA: A single-stranded copy of one gene.

The Central Dogma: DNARNAProtein

Codon 1 Codon 2

Page 27: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA: A long double-stranded string of nucleotides that encode for many genes.

Gene

Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons.

Amino acid 1 Amino acid 2

RNA: A single-stranded copy of one gene.

The Central Dogma: DNARNAProtein

Codon 1 Codon 2

Page 28: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA: A long double-stranded string of nucleotides that encode for many genes.

Gene

Protein: Proteins are composed amino acids. Amino acids are made from triplets of nucleotides called codons.

Amino acid 1 Amino acid 2

Protein!

RNA: A single-stranded copy of one gene.

The Central Dogma: DNARNAProtein

Codon 1 Codon 2

Page 29: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

A small change in the gene sequence can result in a very different protein

ATG GTG CTG TCT CCTDNA:

Page 30: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

A small change in the gene sequence can result in a very different protein

ATG GTG CTG TCT CCT

Met

DNA:

Amino Acids/Protein:

Page 31: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

A small change in the gene sequence can result in a very different protein

ATG GTG CTG TCT CCT

Met

DNA:

Amino Acids/Protein: Val

Page 32: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

A small change in the gene sequence can result in a very different protein

ATG GTG CTG TCT CCT

Met Leu

DNA:

Amino Acids/Protein: Val

Page 33: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

A small change in the gene sequence can result in a very different protein

ATG GTG CTG TCT CCT

Met Leu Ser

DNA:

Amino Acids/Protein: Val

Page 34: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 35: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 36: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

ATG GTG CTG TCT ACTDNA:

Page 37: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

ATG GTG CTG TCT ACT

Met Leu Ser Thr

DNA:

Amino Acids/Protein: Val

Page 38: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 39: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Tom and Sam are sadWords:

Page 40: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Tom and Sam are sadWords:

Changes in DNA are called variations or mutations

Variations in the DNA (genotype) can cause observable changes (phenotype) in individuals

Page 41: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Variationsin our DNA

make usUNIQUE!

Page 42: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

HelpedNo Effect/Hurt

Tumoricide

Why does Tumoricide work on some patients but not

on others?

Page 43: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 44: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Drugs and Receptors

Cell

Page 45: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Drugs and Receptors

Cell

Receptor(Protein)

Page 46: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Drugs and Receptors

Cell

Receptor(Protein)

Page 47: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Drugs and Receptors

Cell

Drug(Ligand) Receptor

(Protein)

Page 48: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Drugs and Receptors

Cell

Drug(Ligand) Receptor

(Protein)

Page 49: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Your DNA and DrugsVariation in genes can cause variation in receptors

Cell

Page 50: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Your DNA and DrugsVariation in genes can cause variation in receptors

Cell

Page 51: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Your DNA and DrugsVariation in genes can cause variation in receptors

Cell

Cell

Cell

Page 52: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Your DNA and DrugsVariation in genes can cause variation in receptors

Cell

Cell

Cell

Cell

Cell

Page 53: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Your DNA and DrugsVariation in genes can cause variation in receptors

Cell

Cell

Cell

Too Many(hypersensitive)

Cell

Cell

Page 54: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Your DNA and DrugsVariation in genes can cause variation in receptors

Cell

Cell

Cell

Too Many(hypersensitive)

Too Few(hyposensitive)

Cell

Cell

Page 55: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Your DNA and DrugsVariation in genes can cause variation in receptors

Cell

Cell

Cell

Cell

Cell

Too Many(hypersensitive)

Too Few(hyposensitive)

Mutated(insensitive)

Page 56: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Where Drugs “Fit” In

Lock = Receptor Key = Drug

Page 57: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Let’s do a class case study!

Page 58: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Let’s do a class case study!

• Taste the PTC strip(This won’t hurt you - not a toxic chemical)

What do you taste?

Page 59: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Let’s do a class case study!

• 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?

Page 60: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Taste cell

“This tastes bitter!”

PTC-Receptor PTC

Why can some people taste PTC and others can’t?

Page 61: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Taste cell

“This tastes bitter!”

PTC-Receptor PTC

Why can some people taste PTC and others can’t?

Taste cell

“I don’t taste anything!”

Non-binding PTC-

ReceptorPTC

Page 62: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Where does tasting PTC come from?You have two copies of every gene:

one from Mom and

one from Dad

Page 63: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Where does tasting PTC come from?You have two copies of every gene:

one from Mom and

one from Dad

Page 64: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Where does tasting PTC come from?You have two copies of every gene:

one from Mom and

one from Dad

Page 65: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

• Your two genes are the genotype

You have two copies of every gene: one from Mom

and one from Dad

Where does tasting PTC come from?

Page 66: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

You have two copies of every gene: one from Mom

and one from Dad

Where does tasting PTC come from?

Page 67: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

You have two copies of every gene: one from Mom

and one from Dad

Where does tasting PTC come from?

Page 68: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

TT Tt tt

Page 69: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

TT Tt tt

Page 70: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

TT Tt tt

Page 71: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

TT Tt tt

Page 72: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

TT Tt tt

For individuals with these genotypes, what would their phenotypes be?

Page 73: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

“This tastes REALLY bitter!”

SUPERTASTER

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

Tt tt

Page 74: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

“This tastes bitter!”

TASTER

“This tastes REALLY bitter!”

SUPERTASTER

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

Tt tt

Page 75: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

“This tastes bitter!”

TASTER

Tasting PTC is dominant (T) over inability taste PTC which is recessive (t)

Tt tt

“I dont taste anything!”

NON-TASTER

“This tastes REALLY bitter!”

SUPERTASTER

Page 76: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Drug receptor summary

Ability to taste PTC has a very strong genetic componentPTC = chemical and Drugs = chemical

Differences in ability to taste PTC is similar to differences in reactions to drugs

PTC

Page 77: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

HelpedNo Effect/Hurt

Tumoricide

Why?

Page 78: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Two Types of Breast Cancer

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

YYYHer2- Her2+

Page 79: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

HelpedNo Effect/Hurt

Tumoricide

Her2- Her2+

Page 80: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Screening for Her2+ Cells

American Journal of Clinical Pathology. 2008;129(2):263-273

Her2- Her2+

Page 81: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Screening for Her2+ Cells

American Journal of Clinical Pathology. 2008;129(2):263-273

+ Tumoricide = ?

Page 82: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Screening for Her2+ Cells

American Journal of Clinical Pathology. 2008;129(2):263-273

+ Tumoricide = ✓

Page 83: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Breast Cancer1990

•Surgery•Radiation•Chemotherapy (drugs)

2012•Surgery•Radiation•Chemotherapy

•Specialized treatments (for certain types of breast cancer)

http://www.ucdmc.ucdavis.edu/welcome/features/20080709_cancer_sweeney/index.html

Page 84: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 85: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Y

The presence of receptors influence how we react to drugs like Tumoricide or chemicals like PTC

Tumoricide Works!

Tumoricide Does Not Work

YHer2- Her2+

Y

Page 86: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

TT Tt tt

“This tastes REALLY bitter!”

SUPERTASTER

“This tastes bitter!”

TASTER

“I dont taste anything!”

NON-TASTER

The presence of receptors influence how we react to drugs like Tumoricide or chemicals like PTC

Page 87: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Where are the PTC receptors?

Page 88: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Where are the PTC receptors?

They are on your taste buds!

Yummy!

Page 89: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 90: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Papillae

bumps on your tongue

Page 91: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Taste buds cells are found on the papilla

Papillae

bumps on your tongue

Page 92: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Taste buds cells are found on the papilla

PTC receptors are found on the taste buds

Papillae

bumps on your tongue

Page 93: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

PTC receptors are found on the taste buds

Papillae

bumps on your tongue

Nerve CellTransmits signal

to brainTaste buds cells are found on the papilla

Page 94: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

PTC receptors are found on the taste buds

Papillae

bumps on your tongue

Nerve CellTransmits signal

to brain

BrainWow! This tastes

really bitter

Taste buds cells are found on the papilla

Page 95: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Are there other traits that can allow a person to more strongly taste PTC?

Page 96: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Are there other traits that can allow a person to more strongly taste PTC?

Page 97: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Let’s test our hypothesis and count our taste buds!

1) Lollipop time! Lick your lollipop such that the blue gets all over your tongue…especially the tip of your tongue.

2) 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.

3) 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. *

Page 98: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Counting the number of tongue papillae

5 papillae 20 papillae 35 papillae

Page 99: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Counting the number of tongue 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

5 papillae 20 papillae 35 papillae

Page 100: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 101: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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!

Page 102: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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?

Page 103: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 104: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 105: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

tastersuper-taster

Page 106: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 107: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

http://publications.nigms.nih.gov/medbydesign/chapter1.html

ADME

• Absorption

• Distribution

• Metabolism

• Excretion

A Drug’s Life

Page 108: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Metabolic enzymes

Liver

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

Drug MetabolitesEnzymes

Page 109: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Adverse Drug Reactions (ADR)• Definition- unwanted, negative response to a prescribed drug

at normal doses and during normal use–Examples?

Page 110: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 111: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 112: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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… A

B

C

Page 113: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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… A

B

C

Why?

Page 114: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

ADME of Nortriptyline

100mg Nortriptyline

Adverse reaction Nothing happens Gets better

A B C

How much active drug in blood?

Page 115: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

ADME of Nortriptyline

100mg Nortriptyline

Adverse reaction Nothing happens Gets better

A B C

95mg 5mg 50mg

Page 116: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA variation influence drug metabolism

Liver

Drug MetabolitesEnzymes

A

Poor Metabolizer

95mg

Page 117: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA variation influence drug metabolism

Liver

Drug MetabolitesEnzymes

B

Ultrarapid Metabolizer

5mg

Page 118: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

DNA variation influence drug metabolism

Liver

Drug MetabolitesEnzymes

C

Intermediate Metabolizer

50mg

Page 119: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

2012 - What do doctors do?

A B C

Decrease Dose Increase Dose

Or change drug

Poor Metabolizer Ultrarapid Metabolizer

Page 120: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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?

Page 121: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

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

Page 122: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

April, 2050You 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-AllFuture = Drugs Specific for You!

More effective & minimizes side effects

Page 123: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

SummaryGenetic variation leads to phenotypic differences and

differences in how we all react to drugs.

Page 124: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

SummaryGenetic variation leads to phenotypic differences and

differences in how we all react to drugs.

1. Having the receptor (protein) to recognize the drug PTC and HER2 receptors

Page 125: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

SummaryGenetic variation leads to phenotypic differences and

differences in how we all react to drugs.

1. 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

Page 126: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

SummaryGenetic variation leads to phenotypic differences and

differences in how we all react to drugs.

1. 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

Page 127: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

Pharamcogenomics Using people’s genetic information for the right

drug at the right dose at the right time!

RX

Page 128: What is DNA? What is DNA Day? April 1953 Drs. James Watson and Francis Crick determined the structure of DNA (double helix)

• What do I study?

• Why do I love science?

• Questions?

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