g e n e t i c s n e w s
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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 - PowerPoint PPT PresentationTRANSCRIPT
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Genetics News• Helen Fillmore talks today on therapies
for neurodegenerative diseases. 12:30. Here.
• Problem Set 10 on line
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On Our PlateGenetics 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
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Demonstration of Clonality
What does the gel represent? (e.g. DNA fragments?)
Protein with G6PD activity
Fig. 1: Analysis of glucose-6-phosphate dehydrogenase (G6PD) protein. Gel electrophoresis of protein samples, staining for G6PD activity. Protein for the left three lanes was taken from subjects with known genotypes. L is the protein sample from the leukocytes of the patient. S is a protein sample from skin cells of the patient. (Adapted from Fialkow et al (1969) Proc Natl Acad Sci USA 163:194-196)
Protein from LeukocytesProtein from Skin cells
What do “L” and “S” represent?
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XBXB and XAXB
Demonstration of Clonality
SQ2 and 3: What is the mother’s genotype?
Why two genotypes?Which was she born with?
XAXB is the germline genotype
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Demonstration of Clonality
SQ4: Why three bands in skin cells?
Lactate dehydrogenase???
1
3
3
1
8
1
2
1
4Glc-6-P dehydrogenase
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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.
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Control over Cell Division
Mitosis
Gap1
DNA synthesis
Gap2
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Control over Cell Division
Build up of signal(cyclin-CDK complex)
What happens if the cell is Rb-?
Hormones
phosphate
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The Menace of Familial Retinoblastoma
Rb dominant
Mutation rare(say 1 in 109)
What is the result of a single Rb- mutation?
What about here?
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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 0Day 1Day 2Day 3Day 4
Ratio of Cell #1:Cell #2 after 30 days?
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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?
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Control over Cell Division
Build up of signal(cyclin-CDK complex)
Hormones
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Signal Transduction:Environmental Signal
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Signal Transduction:Activation of Receptor
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Signal Transduction:Activation of Protein Kinase
Ras
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Signal Transduction:Activation of 2nd Protein Kinase
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Signal Transduction:Activation of 3rd Protein Kinase
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Signal Transduction:Activation of Transcription Factor
E.g. Myc
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Signal Transduction:Activation of Genes
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Signal Transduction:Activation of Receptor
No hormone
Mutant signaltransducing protein
(e.g. Ras)
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Signal Transduction:Activation of Genes
No hormone
Mutant signaltransducing protein
(e.g. Ras)
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Control over Cell Division
Build up of signal(cyclin-CDK complex)
p53
Hormones
Mismatch Repair
Suicide?(Apoptosis)
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Control over Cell Division
Build up of signal(cyclin-CDK complex)
Hormones
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Oncogene vs Tumor Suppressor
OncogenesWhen mutated, stimulates cell division
• RAS - Stimulates protein kinase
• MYC - Transcriptional factor
Tumor suppressorsWhen mutated, releases division to cell block
• RB - Inhibits transcription factor
• P53 - Many functions (e.g. transcription factor)
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Study Question 12
• Protein monitors DNA for DNA damage
• If DNA damaged, protein blocks cell division
Is protein tumor suppressor or from an oncogene?
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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?
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Study Question 15
A B C D
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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 Pimm? Where is it on?