Lecture 16: Toxicogenomics Flashcards
_____: the study of processes at genome-wide scales
omics
what project took 13 years to completely sequence the human genome?
human genome project (2.7 billion)
“_________” Sequencing (high
throughput).
* Faster, better and “affordable”
* In 2022, cost a few million for the
human genome.
Next Generation
T/F: the techniques used for
next generation
sequencing are NOT
species-specific.
true!!
how do we study RNA using NGS sequencing?
have to convert it to cDNA (Complementary DNA created through reverse transcription)
______: Estimate mRNA transcript abundance using RNA-seq.
* Differences in “gene expression”.
Transcriptomics
______: Look at genetic sequence differences using DNA sequencing.
* Single nucleotide polymorphisms (SNPs)
Genomics
T/F: transcriptomics and Genomics use the same tech, just need to prepare samples differently
true!!
transcriptomics allows us to measure mRNA transcript levels for 100’s to 1000’s genes, what did this revolutionize? what kind of research can be done with it
molecular biology, medical research (cancer) and animal biology (toxicology)
transcriptomics turns Individual genes to transcriptome-wide screens, what kind of tests are associated with this process?
microarrays and RNA-sequencing
______ Provides a snapshot as to what was
going on at the time of sampling
transcriptomics
what are some of the potential uses for RNA-sequencing for toxicology?
Can measure gene expression (mRNA transcript
abundance) in individuals from different treatments
or environments.
Start looking at the mechanism. How does a cell or animal
respond to a toxicant?
Start looking at potential causes of physiological stress in wild animals. Are animals responding to a class of toxicants or to contaminant stress in general?
we use RNA-sequencing to examine the mechanisms of toxicants, whats an example of this? what did they find in the study?
effects of DEET on dog ticks
found that exposure to DEET causes
dog ticks to rapidly decrease expression
of Phase I detoxification genes!
also decreased P450 enzyme activity!
ticks actively avoid DEET when they detect it
we use RNA-sequencing to examine the causes of physiological stress in wild animals, whats two example of this? what did they find in the studies?
invasive silver carp- aren’t moving from Chicago to Lake Michigan (pollution barrier??)
longnose dace downstream of wastewater effluent- Disruption of lipid
synthesis at sites
downstream from
wastewater outfall
tracking sources of invasive mosquitos is an example of?
genomics
Tracked the source of 115
Aedes aegypti (can carry
yellow fever) mosquitoes in
ports in Australia and New
Zealand using SNPs.
* ~42K SNPs for each
mosquito.
what mutations did mosquitos found in airports have?
mutations in sodium channels (resistance to pyrethroid pesticides!!)
Can genotype the mosquitoes based on sequence variation in between
source populations using all ~42K SNPs!
measuring pollution tolerance in Atlantic killifish is an example of…
genomics
_______: Short generation time
- Genetically variable
- Nonmigratory
- Small home ranges
- Sequenced genome
- Abundant in coastal marshes
including polluted urban
estuaries in USA
atlantic killifish
locally adaptive
phenotypes may evolve “quickly”!
what was found in the pollution tolerance in Atlantic killifish study?
populations from polluted sites (T) exhibit
tolerance to concentrations hundreds to
thousands of times normally lethal levels
shows a genotype-environment interaction
what happened to the atlantic killifish embryos exposed to PCB pollution?
heart resembles a tube
unable to generate
substantial blood flow
massive pericardial edema
(PE)
Recall that PCBs and Dioxins bind to
the ________
aryl hydrocarbon receptor
________: This is a transcription factor protein.
Once it gets activated, moves into the
nucleus and switches on the
transcription of 60 genes: Phase I
metabolism (CYP4501A1) and Phase
II metabolism (GSTs, etc)
aryl hydrocarbon receptor
why did atlantic killifish have pollution tolerance?
gene deletions, which
results in tolerance to some toxicants in those
populations!!!! (ex: susceptibility factor!!)
studying lampricide use in the Great Lakes is an example of…
genomics
the invasive sea lamprey in the Great Lakes decimated….
fisheries
so… Lampricides applied to rivers and
streams (~9hrs).
* Targets the larvae (i.e., ammocoetes).
* Potential for non-target exposure.
what are the two components of lampricides?
TFM (lamprey specific)
niclosamide (1-2%)
- no specificity (saves $$$)
_______: Interferes with oxidative
phosphorylation
* Inhibits ATP synthesis, leads to ROS
production and necrosis.
* Little known on the effects on
non-target species.
TFM, studied more!!
what are the different treatments for lampricide use in the Great Lakes?
- Control
- TFM (22.06 & 2.21 mg/L)
- Niclosamide (1.5%)
- Mixture
