tox test 2 toxicogenomics

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tox test 2 toxicogenomics
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2013-10-22 15:24:13
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tox test 2 toxicogenomics
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  1. 3 major objectives of toxicogenomics
    • 1. elucidate the connection between environmental stress and disease susceptibility
    • 2. establish proper biomarkers of disease and exposure to toxic substances
    • 3. clarify the molecular mechanism of toxicity
  2. 3 advances in technologies that have accelereated discovery of toxicant pathways
    • cDNA microarrays
    • protein chips
    • nuclear magnetic resonance profiling
  3. pharmacogenetics
    study of how genetic attributes results in disparity in an individual's response to drugs
  4. pharmacogenomics
    associated with the detection and determination of the genome and its products as they are linked to drug response
  5. reaction to  specific medicine is impacted by an individual's version of a gene, which may alter what
    • pharmacokinetics
    • pharmacodynamics
  6. 5 mechanisms that account for genetic variation
    • nucleotide substitutions
    • insertion or deletion of nucleotides
    • alterations in # of tandem-repeat sequences
    • variations in copy number of genomic segments
    • combo of any of the above
  7. a subtype of genetic variations that occurs at a frequency of > 1% in a population
    polymorphism
  8. 6 DNA-related polymorphisms
    • restriction fragment length
    • variable # of tandem repeat
    • short tandem repeat
    • single-nucleotide
    • copy number variation
    • epigenetics
  9. variations in the size of the DNA fragment digested by restriction endonucleases due to the base substitutions at the site identified by the endonuclease
    RFLP
  10. 3 applications of RFLP
    • used in paternity cases or criminal cases
    • determine disease status of an individual
    • create a genetic map
  11. 3 consequences of increased homocysteine levels
    • increased risk of thrombosis
    • increased risk of alzheimers disease
    • increased cardiovascular disease
  12. example of RFLP in detection of mutation in disease states
    methyl tetrahydrofolate reductase = increased levels of homocysteine as a result of impaired ability to process folate
  13. 5 causes of elevated homocysteine levels
    • deficiency of B vitamins and folate in diets
    • kidney disease
    • low levels of thyroid hormones
    • meds - antiepileptic & methotrexate
    • genetic variations
  14. enzyme used to metabolize plavix
    CYP2C19
  15. 3 benefits toxicogenomics provides
    • 1. more detailed appreciation of the molecular mechanisms of toxicity
    • 2. faster & more cost effective screening tool
    • 3. enhanced extrapolation between experimental animals and humans in the context of risk assessment

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