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DNA Day - Pharmacogenetics1. Todays Plan! What is DNA? Genetic Wheel Activity What is Pharmacogenomics? Super taster activity! How do drugs work? Wrap.

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Presentation on theme: "DNA Day - Pharmacogenetics1. Todays Plan! What is DNA? Genetic Wheel Activity What is Pharmacogenomics? Super taster activity! How do drugs work? Wrap."— Presentation transcript:

1 DNA Day - Pharmacogenetics1

2 Todays Plan! What is DNA? Genetic Wheel Activity What is Pharmacogenomics? Super taster activity! How do drugs work? Wrap up and future science careers

3 3 On April 25, 1953 Drs. James Watson and Francis Crick determined the structure of DNA In April 2003, Human Genome Project determined the entire DNA sequence of a human (3 billion letters) Genome: the complete set of hereditary factors What is DNA Day?

4 Protein RNA copy Information is stored in DNA Genes contain instructions to make proteins Proteins do most of the work in a cell and provide much of its structure.

5 5 A change in gene result in a change in protein SAM AND TOM ATE THE HAM Change: SAM AND TOM ATE THE HIM ThrProGlu LysLeu ACT | CCT | GAG | GAG | AAG | CTG ACT | CCT | GAG | GAG | AAG | CGG ThrProGlu LysMet Result: Changed meaning or function Change in DNA is called a mutation Variations in the DNA of different individuals can cause phenotypic changes in individuals

6 DNA Day - Pharmacogenetics6 Why do people look different? Genetic variation –Eye color - common genetic variation –Downs syndrome (trisomy 21) - rare genetic variation Environment –Diet –Exercise

7 Mendelian traits Phenotype: Cleft Chin Genotype: cc Phenotype: non-cleft chin Genotype: CC or Cc Example

8 Mendelian traits Phenotype: Cleft Chin Genotype: cc Example C c Cc Mom Dad What are mom and dads phenotype if their genotype is Cc? Non cleft chin CC CcCc CcCc cc Name the phenotypes of their potential children.

9 Just by looking around the room, we can see many examples of genetic variation. Some genetic traits, such as skin color and eye color, are controlled by multiple genes Others are controlled by only one gene We are going to look at 7 traits that are each determined by one gene with two possible alleles. Variations in the DNA of different individuals can cause visible changes in individuals

10 Single-gene Traits Laugh dimples ll no dimples (homozygous recessive) L dimples (heterozygous or homozygous dominant) Tongue roll tt cant roll tongue into U shape (homozygous recessive) T can roll tongue into U shape (heterozygous or homozygous dominant )

11 Single-gene Traits Crossing Thumbs cc right thumb on top of clasped hands (homozygous recessive) C left thumb on top of clasped hands (heterozygous or homozygous dominant ) Pinkies pp pinkies are straight when pressed side by side (homozygous recessive) P pinkies bend away from each other, toward the ring fingers, when pressed side by side (heterozygous or homozygous dominant)

12 Single-gene Traits Ear lobes ee attached ear lobe (homozygous recessive) E free ear lobe (heterozygous or homozygous dominant) Widows peak ww no widows peak (homozygous recessive) W has a widows peak (heterozygous or homozygous dominant)

13 Single-gene Traits Bending thumbs (Hitch-hikers thumb) bb thumb bends at 90 degree angle (homozygous recessive) B thumb is straight (heterozygous or homozygous dominant)

14

15 99

16 79 99

17 Genetic Wheel Results There are 128 possible combinations from the 7 traits illustrated on the genetic wheel. Are you the same as anyone else? If this much genetic variation exists in traits that are visible, imagine how different we all are in ways that we cant see!

18 DNA summary DNA RNA protein : changes in DNA can lead to changes in protein function and phenotype Genetic differences are inherited phenotypes are inherited Differences in genetics also affect an individuals response to drugs

19 DNA Day - Pharmacogenetics19 What is Pharmacogenomics? Personalized medicine tailored to your genes Pharma = drug or medicine Genomics = the study of genes

20 DNA Day - Pharmacogenetics20 Different responses to drugs Benefits: pain relief, prevents heart attacks Side effects: GI bleeding, Reyes syndrome Aspirin

21 What are ways a person would react differently to drugs? 1.Whether you have the protein to recognize the drug 2.Number of the proteins that recognize the drug 3.How your body processes the drugs after receiving it DNA Day - Pharmacogenetics21

22 What proteins recognize a drug (chemical)? Receptors. 22 Drugs bind drug receptors on cells to cause effects - drug = key - receptor = lock Genetic variation can cause variation in drug receptors Cell Drug (eg. Aspirin) Receptor (protein)

23 DNA Day - Pharmacogenetics 23 Therapeutic response Therapeutic response : NOTHING! Pharmacogenomics being used TODAY! Breast CancerCell Drug that fits in the receptor is like a key in a lock Therapeutic response: Death of Cancer Cell Her2 Receptor This breast cancer cell is considered Her2+ and the receptor can fit drugs made for it! This breast cancer cell is considered Her2- and there is no receptor for the drug!

24 Herceptin is a personalized medication Breast cancer tumors can be divided into 2 classes: Her2+ or Her2- Herceptin only works for Her2+ breast tumors

25 DNA Day - Pharmacogenetics 25 Taste this PTC strip This wont hurt you - not a toxic chemical What did you taste? Why did the strip taste bitter to one person and have no taste for another? Hypothesis?

26 DNA Day - Pharmacogenetics 26 PTC Punnett square Ability to taste PTC (T) is dominant over inability to taste PTC (t) 70% of population can taste PTC (TT or Tt), 30% cant (tt) Moms genotype is Tt and Dads genotype is Tt. What could their kids be? T t Tt TT :-(Tt :-| tt :-)

27 Why can some people taste PTC and others cant? A key must fit into the lock to open a door A drug must be able to bind the receptor to cause an effect One genetic variant of the PTC receptor (PTC-R) binds PTC well - PTC tastes bitter One genetic variant of PTC-R cant bind PTC- no taste- key doesnt fit lock! Taste cell This tastes bitter! PTC PTC-R Taste cell Y I dont taste anything!

28 DNA Day - Pharmacogenetics 28 Why can some people taste PTC and others cant? Y This tastes bitter! TASTER This tastes REALLY bitter!!!! SUPERTASTER Y I dont taste anything! Taste cell NON-TASTER Y Taste cell

29 DNA Day - Pharmacogenetics 29 Drug receptor summary Ability to taste PTC has a very strong genetic component PTC = chemical Drugs = chemical Differences in ability to taste PTC is similar to differences in reactions to drugs Now lets do an activity to test a hypothesis!!

30 What are ways a person would react differently to drugs? 1.Whether you have the protein to recognize the drug 2.Number of the proteins that recognize the drug (receptors) 3.How your body processes the drugs after receiving it DNA Day - Pharmacogenetics 30

31 Does everyone have the same number of receptors?? DNA Day - Pharmacogenetics 31

32 DNA Day - Pharmacogenetics32 Tongue Anatomy

33 How do you think the number of taste buds will vary with tasting PTC?

34 DNA Day - Pharmacogenetics 34 Counting taste bud density 1.Swirl the blue water in your mouth and spit back into cup 2.Place paper-hole reinforcer on the tip of tongue 3.The blue dye will stain everywhere except for taste buds

35 DNA Day - Pharmacogenetics35 Counting taste bud density 4. Use a flashlight and magnifying glass to count the number of taste bud inside the hole Examples 5 20 35

36 DNA Day - Pharmacogenetics36 Go to excel file

37 DNA Day - Pharmacogenetics 37 What does it take to be a PTC Taster? PTC tasting genotype = PTC receptors that can bind PTC High density of taste buds 5 20 35

38 DNA Day - Pharmacogenetics38 PTC activity summary People vary in PTC genotype, therefore people vary in their tasting of PTC More tastebuds = greater ability to taste PTC (drug) Listen to NPR sound file How do drugs work in your body?

39 What are ways a person would react differently to drugs? 1.Whether you have the protein to recognize the drug 2.Number of the proteins that recognize the drug 3.How your body processes the drugs after receiving it DNA Day - Pharmacogenetics 39

40 How does the body process drugs? Absorption Distribution Metabolism Excretion

41 DNA Day - Pharmacogenetics41 Today: April, 2011 Three women of the same height, weight, and age are depressed and go to the doctor. The doctor prescribes an antidepressant, Nortripyline, at a dose of 100 mg. Person A has an adverse reaction Person B nothing happens Person C gets better…

42 DNA Day - Pharmacogenetics42 Adverse Drug Reactions (ADR) Definition- unwanted, negative reaction to a prescribed drug –Examples There are multiple causes for ADRs –Some ADRs have a genetic basis –Some ADRs may have an environmental basis Poor metabolizers can experience ADRs at normally therapeutic drug doses

43 DNA Day - Pharmacogenetics43 Genetic differences = variable drug metabolism Person A has an adverse reaction Person B nothing happens Person C gets better… A Give 100 mg Nortriptyline to each BC Measure mg nortriptyline in blood after 8 h 95 mg5 mg50 mg

44 DNA Day - Pharmacogenetics 44 2011 -What do we do? Person A has an adverse reaction - Change dose/drug Person B nothing happens - Change dose/drug Person C gets better… A Give 100 mg Nortriptyline to each BC Measure mg nortriptyline in blood after 8 h 95 mg5 mg50 mg

45 DNA Day - Pharmacogenetics 45 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)

46 DNA Day - Pharmacogenetics 46 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

47 DNA Day - Pharmacogenetics 47 Take home messages Genetic variation leads to phenotypic differences and differences in how we all process drugs Drugs are processed in the body Todays medicines are one-size fits all Soon, we can tailor drugs to be specific to a persons genetics

48 END OF PRESENTATION FEEL FREE TO DISCUSS YOUR RESEARCH AND CAREERS

49 Herceptin uses the immune system to kill tumor cells.


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