DNA MicroArrays by dffhrtcv3


									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

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

           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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