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Measurement of gene expression profiles in toxicity determination

  • US 6,228,589 B1
  • Filed: 02/28/2000
  • Issued: 05/08/2001
  • Est. Priority Date: 10/11/1996
  • Status: Expired due to Term
First Claim
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1. A method of determining the toxicity of a compound, the method comprising the steps of:

  • administering the compound to a test organism;

    extracting a population of mRNA molecules from each of one or more tissues of the test organism;

    forming a separate population of cDNA molecule from each population of mRNA molecules from the one or more tissues such that each cDNA molecule of the separate populations has an oligonucleotide tag attached, the oligonucleotide tags being selected from the same minimally cross-hybridizing set;

    separately sampling each separate population of cDNA molecules such that substantially all different cDNA molecules within a sample have different oligonucleotide tags attached;

    sorting the cDNA molecules of each sample by specifically hybridizing the oligonucleotide tags with their respective complements, the respective complements being attached as uniform populations of substantially identical complements in spatially discrete regions on one or more solid phase supports;

    determining the nucleotide sequence of a portion of each of the sorted cDNA molecules of each separate population to form a frequency distribution of expressed genes for each of the one or more tissues; and

    determining the toxicity of the compound from the frequency distribution of expressed genes in each of the one or more tissues.

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