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Today’s Plan!

Today’s Plan!. What is DNA? Genetic Wheel Activity What is Pharmacogenomics? Super taster activity! How do drugs work? Wrap up and future science careers . What is DNA Day?. On April 25, 1953 Drs. James Watson and Francis Crick determined the structure of DNA. In April 2003,

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Today’s Plan!

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  1. DNA Day - Pharmacogenetics

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

  3. What is DNA Day? 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

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

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

  6. Why do people look different? • Genetic variation • Eye color - common genetic variation • Down’s syndrome (trisomy 21) - rare genetic variation • Environment • Diet • Exercise DNA Day - Pharmacogenetics

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

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

  9. Variations in the DNA of different individuals can cause visible changes in individuals • 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.

  10. Single-gene Traits Tongue roll tt can’t roll tongue into “U” shape (homozygous recessive) T can roll tongue into “U” shape (heterozygous or homozygous dominant ) Laugh dimples • ll no dimples (homozygous recessive) • L dimples (heterozygous or homozygous dominant)

  11. Single-gene Traits 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) Crossing Thumbs • cc right thumb on top of clasped hands (homozygous recessive) • C left thumb on top of clasped hands (heterozygous or homozygous dominant )

  12. Single-geneTraits Widow’s peak ww no widow’s peak (homozygous recessive) W has a widow’s peak (heterozygous or homozygous dominant) Ear lobes • ee attached ear lobe (homozygous recessive) • E free ear lobe (heterozygous or homozygous dominant)

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

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  16. 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 can’t see!

  17. 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 individual’s response to drugs

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

  19. Different responses to drugs • Benefits: pain relief, prevents heart attacks • Side effects: GI bleeding, Reye’s syndrome Aspirin DNA Day - Pharmacogenetics

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

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

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

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

  24. Taste this PTC strip • This won’t 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? DNA Day - Pharmacogenetics

  25. T t T TT :-( Tt :-| t Tt :-| tt :-) 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% can’t (tt) • Mom’s genotype is Tt and Dad’s genotype is Tt. What could their kids be? DNA Day - Pharmacogenetics

  26. Why can some people taste PTC and others can’t? PTC • 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 can’t bind PTC- no taste- key doesn’t fit lock! PTC-R Taste cell “This tastes bitter!” Y Taste cell “I don’t taste anything!”

  27. Taste cell Taste cell Taste cell Why can some people taste PTC and others can’t? Y Y Y “I don’t taste anything!” “This tastes bitter!” “This tastes REALLY bitter!!!!” NON-TASTER TASTER SUPERTASTER DNA Day - Pharmacogenetics

  28. 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 let’s do an activity to test a hypothesis!! DNA Day - Pharmacogenetics

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

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

  31. Tongue Anatomy DNA Day - Pharmacogenetics

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

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

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

  35. Go to excel file DNA Day - Pharmacogenetics

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

  37. 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? DNA Day - Pharmacogenetics

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

  39. Absorption • Distribution • Metabolism • Excretion How does the body process drugs?

  40. 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… DNA Day - Pharmacogenetics

  41. 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 DNA Day - Pharmacogenetics

  42. 95 mg 5 mg 50 mg Measure mg nortriptyline in blood after 8 h Genetic differences = variable drug metabolism Give 100 mg Nortriptyline to each • Person A has an adverse reaction • Person B nothing happens • Person C gets better… A B C DNA Day - Pharmacogenetics

  43. 95 mg 5 mg 50 mg Measure mg nortriptyline in blood after 8 h 2011 -What do we do? Give 100 mg Nortriptyline to each • Person A has an adverse reaction - Change dose/drug • Person B nothing happens - Change dose/drug • Person C gets better… A B C DNA Day - Pharmacogenetics

  44. 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) DNA Day - Pharmacogenetics

  45. 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 DNA Day - Pharmacogenetics

  46. Take home messages • Genetic variation leads to phenotypic differences and differences in how we all process drugs • Drugs are processed in the body • Today’s medicines are one-size fits all • Soon, we can tailor drugs to be specific to a person’s genetics DNA Day - Pharmacogenetics

  47. END OF PRESENTATION FEEL FREE TO DISCUSS YOUR RESEARCH AND CAREERS

  48. Herceptin uses the immune system to kill tumor cells.

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