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Slides Slides Presentation Transcript

  • G e n e t i c s N e w s
    • Helen Fillmore talks today on therapies for neurodegenerative diseases. 12:30. Here.
    • Problem Set 10 on line
  • On Our Plate Genetics of Cancer
    • Clonal Nature of Cancer
    • G6PD experiment
    • Somatic vs. Germline Mutation
    • RB: A Tumor Suppressor Gene
    • Signal Transduction
    • Oncogenes & Tumor Suppressors
    • Progression of Cancer
  • Demonstration of Clonality What does the gel represent? (e.g. DNA fragments?) Protein with G6PD activity Protein from L eukocytes Protein from S kin cells What do “L” and “S” represent?
  • Demonstration of Clonality X B X B and X A X B SQ2 and 3: What is the mother’s genotype? Why two genotypes? Which was she born with? X A X B is the germline genotype
  • Demonstration of Clonality SQ4: Why three bands in skin cells? Lactate dehydrogenase??? 1 3 3 1 8 1 2 1 4 Glc-6-P dehydrogenase
  • Cancer: Infection or Clonal? What is meant by “A” and “B”? Why do some cells have “A” and others have “B”? Why do cells in panel C have a mixture of cell types? Why do cells in panel B have the same cell type? Fig. 2. Two models to explain cancer . ... Half of the cells have an active X chromosome carrying the A allele and half have an active X chromosome carrying the B allele.
  • Control over Cell Division Mitosis Gap1 DNA synthesis Gap2
  • Control over Cell Division Build up of signal (cyclin-CDK complex) What happens if the cell is Rb - ? Hormones phosphate
  • The Menace of Familial Retinoblastoma Rb dominant Mutation rare (say 1 in 10 9 ) What is the result of a single Rb - mutation? What about here?
  • Study Question 9 Cell #1: Suddenly loses eye pigment enzyme Cell #2: Suddenly loses Rb Normal retinal cells don’t divide Derepressed cells divide once a day Cell #1 Cell #2 Day 0 Day 1 Day 2 Day 3 Day 4 Ratio of Cell #1:Cell #2 after 30 days?
  • Study Question 8
    • Loss of RB in retinal cells causes retinoblastoma
    • Sporadic cases show tumors only in one eye
    • Inherited cases show tumors occur often in both eyes
    • WHY?
  • Control over Cell Division Build up of signal (cyclin-CDK complex) Hormones
  • Signal Transduction: Environmental Signal
  • Signal Transduction: Activation of Receptor
  • Signal Transduction: Activation of Protein Kinase Ras
  • Signal Transduction: Activation of 2 nd Protein Kinase
  • Signal Transduction: Activation of 3 rd Protein Kinase
  • Signal Transduction: Activation of Transcription Factor E.g. Myc
  • Signal Transduction: Activation of Genes
  • Signal Transduction: Activation of Receptor No hormone Mutant signal transducing protein (e.g. Ras)
  • Signal Transduction: Activation of Genes No hormone Mutant signal transducing protein (e.g. Ras)
  • Control over Cell Division Build up of signal (cyclin-CDK complex) p53 Hormones Mismatch Repair Suicide? (Apoptosis)
  • Control over Cell Division Build up of signal (cyclin-CDK complex) Hormones
  • Oncogene vs Tumor Suppressor
    • Oncogenes When mutated, stimulates cell division
    • RAS - Stimulates protein kinase
    • MYC - Transcriptional factor
    • Tumor suppressors When mutated, releases division to cell block
    • RB - Inhibits transcription factor
    • P53 - Many functions (e.g. transcription factor)
  • Study Question 12
    • Protein monitors DNA for DNA damage
    • If DNA damaged, protein blocks cell division
    • Is protein tumor suppressor or from an oncogene?
  • Study Question 15 Lots of p53 mutations in dead people. WHY? A. p53 is prone to mutation? B. p53 is not prone to mutation, but leads to death? C. p53 related to feedback?
  • Study Question 15 A B C D
  • Causes of Particular Cancers Study Question 13 Why does the chromosome 8/14 translocation lead specifically to lymphomas? What is myc ? What’s its threat? What is P imm ? Where is it on?