Genome 371 Lecture 17 - Genome 371 Lecture 17 1/26/11 4:17...

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1/26/11 4:17 PM Genome 371 Lecture 17 Page 1 of 10 http://courses.washington.edu/au371mkr/resources/lecture_notes/lecture_17.html Lecture 17 Analysis of gene function 3 Dec 2010 Lecture 17 handout (pdf) Subscribe to podcast: 3-part PBS video on testing for BRCA1 " Target Cancer ": New York Times series on a proto-oncogene and the search for a drug treatment Slide 1 Slide 2 Home Course mechanics Help hours Calendar Syllabus Lectures, Podcasts Quiz Sections Practice problems Exams GoPost Send email to class Useful links The Gradiator
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1/26/11 4:17 PM Genome 371 Lecture 17 Page 2 of 10 http://courses.washington.edu/au371mkr/resources/lecture_notes/lecture_17.html Slide 3 Slide 4 Slide 5 Somatic cell hybrid experiments (where cultured cells are fused together) validated the predictions made on the previous slide. Slide 6
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1/26/11 4:17 PM Genome 371 Lecture 17 Page 3 of 10 http://courses.washington.edu/au371mkr/resources/lecture_notes/lecture_17.html Slide 7 Most instances of LOH involve large-scale events such as non-disjunction or deletions (in somatic cells), e.g., in individuals 1 and 3 in experiment B of Quiz Section 9. Even in individuals 2 and 4 in that experiment, there presumably was LOH in the cancer cells. .. but that LOH was not detected in the particular genotyping test that was performed. As discussed in class, this particular test was looking at a polymorphic site within an inton; there are many possible scenarios to explain how there could be LOH of the BRCA1 gene while still showing two alleles at this polymorphic site. Slide 8 So how to explain the paradox between the apparent dominant transmission of cancer susceptibility and the expected recessive behavior of the mutated BRCA1 allele? The key is in remembering that LOH happens at the somatic cell level. In a person who has inherited a mutated BRCA1 allele, every cell in the body has alreay suffered one "hit" in the sense that one copy of BRCA1 already is non- functional. All it takes is loss of the other (functioning) BRCA1 allele in any one cell in the body; that cell can then take off and start dividing (or more likely, progress down the path toward cancer). The probability of the LOH event occurring in any one particular cell is low; but because there are so many millions/billions of cells in the tissue/body, there are many millions/billions of "chances" for one LOH event to occur. Slide 9 Slide 10
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1/26/11 4:17 PM Genome 371 Lecture 17 Page 4 of 10 http://courses.washington.edu/au371mkr/resources/lecture_notes/lecture_17.html Slide 11 Slide 12 Slide 13 Slides 14 and 15 For your interest: As an alternative to gene knockouts, "knockdown" techniques have been developed in the 10 years or so. These techniques rely on inhibiting some step of gene expression for particular target genes -- e.g., using "RNAi" (for "RNA intereference") to target the mRNAs of specific genes for destruction. RNAi-based knockdown relies on innate defense mechanisms that cells have against viral and transposon RNA -- they recognize small snippets of double-
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This note was uploaded on 03/31/2011 for the course GENOME 371 taught by Professor Unsure during the Spring '03 term at University of Washington.

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Genome 371 Lecture 17 - Genome 371 Lecture 17 1/26/11 4:17...

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