Pathophys Exam 3

  1. Receptors exist in
    3 different forms
  2. Drug targets are
    • receptors
    • enzymes
  3. The term pharmacogenomics was termed in
  4. Human genome project
    • project to map the human genome
    • >26,000 genes
  5. GWAS
    genome wide association studies
  6. Goals for personalized medicine
    • identify genetic differences in people that affect drug response
    • develope genetic tests that predict an individual's response to a drug
    • tailor treatments to the individual
  7. Pharmacogenetics
    evaluation of how an individual's genetic make-up corresponds to their response to a medication
  8. Pharmacogenomics
    • combines pharmacogenetics with genomic studies
    • uses large groups of patients to evaluate how candidate drugs interact with a range of genes and their protein products
  9. A combination of alleles (for different genes) that are located closely together on the same chromosome and that tend to be inherited together
  10. _____ are those expressed in DNA sequences that become the mRNA
  11. A___ is found in the cell nucleus and consists of one very long DNA molecule and associated proteins
  12. The exchange of one nucleotide for another. Considered the most common genetic variation in human DNA, occurring approximately once in every 300 base pairs.
    Single nucleotide polymorphism
  13. A double-stranded, helical nucleic acid molecule capable of replicating and determining the inherited structure of a cell's proteins
  14. Genetic variations that occur at a frequency of at least 1% in the human population
  15. _____ are those intervening sequences of DNA that are removed in the process of making a mature mRNA.
  16. The genetic makeup of an organism
  17. a section of DNA or RNA that is 3 nucleotide pairs in length that codes for a single amino acid.
  18. physiological trains of an organism
  19. alternate version of a gene
  20. a rare (occurs in <1% of the population) change in the DNA of a gene ultimately creating genetic diversity.
  21. A unit of heredity in a living organism
  22. Percentage of our DNA that is the same as a monkey
  23. Percentage of our DNA that is the same in humans
  24. If all DNA in the body is streched out it is
    6 ft long
  25. Why do we care so much about proteins?
    • essential components of living cells
    • necessary for building and repair of body tissues
    • drug transporters
    • metabolic enzymes
    • receptors
  26. Alternative versions of genes are
  27. DNA at a specific location can vary in nucleotide sequence meaning it varies in
  28. Percentage of DNA that is "junk DNA" or introns which regulate transcription
  29. Percentage of DNA that is exons or expressed traits
  30. Single nucleotide polymorphism (SNPs)
    • most abundant type of genetic variation
    • ~1 SNP in every 300-500 bp
    • ~10,000,000 SNPs in the human genome
  31. Number of SNPs in the coding DNA (exons)
  32. Mechanisms by which SNPs may affect genes even if located in introns
    • DNA stability
    • Folding/unfolding
    • gene spacing
  33. Other types of polymorphisms
    • more than one nucleotide change
    • entire gene insertion or deletion
    • extra copies of a gene
  34. Types of Genetic variations
    • Insertion
    • deletion
    • base pair change
  35. how are SNPs relevent to a pharmacist?
    • SNP change the amount/function of a protein that contributes to drug response
    • may alter pt sensitivity to a drug
    • may cause adverse reactions to a drug
  36. Polymorphism with no effect
    • no change in translated amino acid
    • codon encodes for the same amino acid
    • corruption of the genetic code
    • no functional significance of amino acid substitution
  37. Minimal effect polymorphism
    amino acid substitution results in minimal differences in protein structure or function
  38. significant effect of polymorphism
    • amino acid substitution results in significantly altered protein structure or function
    • altered substrate affinity of CYP450 enzyme
  39. Systems for pharmacogenomic nomenclature
    • allele numeric/alphabetic
    • SNP nomenclature
    • allele "star"nomenclature
    • genotype nomenclature
    • haplotype nomenclature
  40. What is an allele?
    • variant and wild type forms of a gene at a particular location on a chormosome
    • each nucleotide base in the gene can be considered an allele
  41. Allele numeric/alphabetic nomenclature
    • first letters/numbers are the gene
    • numbers indicate the location on the nucleotide
    • C and T represents a nucleotide
  42. SNP nomenclature
    VKORC1 1173 C>T
    • easiest to understand
    • letters = gene
    • numbers = nucleotide
    • first letter = original nucleotide
    • second letter = change that was made
  43. Allele "star" nomenclature CYP2C19*1
    • first letters identify the gene
    • * and number after designate the allele
  44. CYP2C19*1 allele
    normal or wilde type enzyme activity
  45. CYP2C19*2 allele
    = no enzymatic activity
  46. CYP2C19*3 allele
    no enzymatic activity
  47. CYP2C9*1
    normal wild type enzyme activity
  48. CYP2C9*2
    decreased enzymatic activity
  49. CYP2C9*3
    decreased activity
  50. An example of a SNP is the VKORC1 1173 C>T. Based on the pharmacogenomic nomenclature of this SNP, what is the gene of interest?

    C. VKORC1
  51. What is a genotype?
    2 alleles that any individual has
  52. If you see *#/*# then
    we are looking deeper to find if there is a difference in the genotype
  53. What is a haplotype?
    a set of alleles at multiple locations that coexist on the same chromosome
  54. Synonymous SNP
    results in the same amino acid being transcribed
  55. Non-synonymous SNPs
    result in amino acid substitution
  56. A polymorphism has been found for a drug-metabolizing enzyme. A nucleotide change occurs, yet the resultant amino acid is unchanged. What type of SNP is this?

    B. Synonymous
  57. A polymorphism has been found for a drug metabolizing enzyme. A nucleotide change occurs, resulting in a change in the amino acid. What type of SNP is this?

    C. Non-synonymous
  58. When patients have haplotype 7 & 2 they have a reduction in response to statins by
  59. What is the ultimate goal of pharmacogenetics
    use genetic info to choose a drug, dose and treatment duration best for the patient
Card Set
Pathophys Exam 3