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					DNA Microarrays
Examining Gene Expression
              DNA MicroArrays
   DNA MicroArrays use hybridization technology to
    examine gene expression
   Attach different DNAs onto a slide as a grid of small
    spots, one for each gene - up to 50,000 per slide
   Hybridize a mixture of fluorescently labeled cDNAs
    extracted from cells after different treatments - control
    is green and experimental is red
   Examine expression patterns by looking at levels of
    fluorescence for all genes in array


Biology 4                                              Prof. Gross
    DNA MicroArray Hybridization Data
                    each spot corresponds to a different gene

mRNAs at lower
levels in treated
cells are green,
those at higher
levels in treated
cells are red,
those that are
unchanged are
yellow.
                                                                decreased
                                                                expression

                            increased
                           expression
Biology 4                                                             Prof. Gross
  Some Uses of DNA MicroArrays

      Rapid scanning of DNA or RNA populations
      Used for identifying bacterial infections in hospitals
      Used in research on molecular biology of gene expression
      Stanford MicroArray Database (SMD) - gene expression
       information and extensive database of results




Biology 4                                                       Prof. Gross
            Tumor Subgroup Clusters




Biology 4         Perou, et al Nature 406:747 (2000)   Prof. Gross
                         Tumor Clusters

  basal                   normal
expression    Erb-B2+   breast-like                                   Luminal epithelial/ER+




  Biology 4                           Perou, et al Nature 406:747 (2000)                       Prof. Gross
                 Tumor Portraits
   Breast tumors are histologically diverse and differ in their
    responsiveness to treatments
   The expression profiles provided a distinctive molecular
    portrait of each tumor subtype
   Gene expression patterns in two tumor samples from the same
    individual were more similar to each other than either was to
    any other sample
   Sets of co-expressed genes (portraits) were identified that were
    correlated with specific features or physiological variation
   Metastases and primary tumors had similar expression profiles
   Can lead to more effective chemotherapy decisions



Biology 4              Perou, et al Nature 406:747 (2000)    Prof. Gross
                 Pharmacogenomics

           examine expression profile of patient
           compare to known profiles
           determine most effective treatment for
            this particular allele
           designing drugs for individuals




Biology 4                                            Prof. Gross
                     Some Questions
       If pharmacogenomics tests are not done prior to treatment, can
        doctor/drug company be sued?
       If tests are expensive, and patients pay for them, is this a kind of
        “economic” discrimination?
       If patient pays for test is she/he “hiding” information from insurance
        company and subject to having policy cancelled?
       If insurance company pays for test do they have a right to the results?
       From a business perspective, doesn’t it make sense for an insurance
        company to pay for the tests since it might result in avoidance of cancer
        (a big bill!)?
       Discover of “accidental” information in a gene expression profile
        analysis of a patient – should the patient be told?


Biology 4                                                                      Prof. Gross

				
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