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
3 advances in technologies that have accelereated discovery of toxicant pathways
cDNA microarrays
protein chips
nuclear magnetic resonance profiling
pharmacogenetics
study of how genetic attributes results in disparity in an individual's response to drugs
pharmacogenomics
associated with the detection and determination of the genome and its products as they are linked to drug response
reaction to specific medicine is impacted by an individual's version of a gene, which may alter what
pharmacokinetics
pharmacodynamics
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
a subtype of genetic variations that occurs at a frequency of > 1% in a population
polymorphism
6 DNA-related polymorphisms
restriction fragment length
variable # of tandem repeat
short tandem repeat
single-nucleotide
copy number variation
epigenetics
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
3 applications of RFLP
used in paternity cases or criminal cases
determine disease status of an individual
create a genetic map
3 consequences of increased homocysteine levels
increased risk of thrombosis
increased risk of alzheimers disease
increased cardiovascular disease
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
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
enzyme used to metabolize plavix
CYP2C19
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