![Page 1: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/1.jpg)
At the crossroads of genomics and ecology: The potential for a canary on a chip
![Page 2: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/2.jpg)
Genomics and Environmental Protection
• The new age of genomics
![Page 3: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/3.jpg)
Genomics and Environmental Protection
• The new age of genomics
• Applications of genomics data to human health
![Page 4: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/4.jpg)
Genomics and Environmental Protection
• What is genomics?
• Applications of genomics data to human health
• Applications of genomics data to environmental health
![Page 5: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/5.jpg)
The new age of genomics
– A genome is the sum total of all an individual organism’s genes.
– Thus, genomics analysis is the study of all the genes of a cell or tissue, at the DNA (genotype), mRNA (transcriptome), or protein (proteome) levels and can aid in understanding normal, adaptive, and abnormal cellular functions.
EPA definition 2002
![Page 6: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/6.jpg)
![Page 7: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/7.jpg)
A B
![Page 8: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/8.jpg)
Cluster Analysis of Genome-Wide Expression Patterns
![Page 9: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/9.jpg)
cDNA Mechanism Enzyme
YJR159W sorbitol metabolism sorbitol dehydrogenase YGL017W protein synthesis tRNA transferase
YEL008W unknown unknown YFL013C unknown unknown; similar Ifh1p,Nab3p YOL014W unknown unknown YGR144W thiamine biosyn unknown enzyme
YGL177W unknown unknown YDR372C unknown unknown YMR019W transcription Sin3-bind. protein YNR071C unknown UDPglucose 4-epimerase
YLR054C unknown unknown YAR002C-A membrane traffic secretious enzyme-unknown YMR273C cell cycle plasma membrane protein
![Page 10: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/10.jpg)
Other promising field:Proteomics
• Proteomics- identifies and quantifies proteins, determines the localization, modifications, interactions, activities, and, ultimately, the function of proteins.
• Limited use due to need for sequence information and expense
![Page 11: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/11.jpg)
![Page 12: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/12.jpg)
Toxicogenomics
• Gene expression may be altered during toxicity or as a result of a disease
• Measure associated changes in gene expression• More sensitive, characteristic and measureable
endpoint than toxicity itself• Compliments existing methods
![Page 13: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/13.jpg)
Toxicogenomics
• Determine mechanism of action– Genes associated with particular pathways
• Create toxic signature– Don’t necessarily need to know genes
![Page 14: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/14.jpg)
Expression is not Enough
• Changes in mRNA, protein or metabolic levels may also be nonspecific indicators of exposure to any stress without ties to a negative outcome.
• To be meaningful toxicogenomics indicators, gene or protein expression must be linked to pathways as well as the overall phenotypic effects
• Expression can be affected by diet, health, behavior, environment
![Page 15: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/15.jpg)
Genomics and Human Health
• Drug discovery and drug safety• Genetics and disease• Genetics x Environment link• Environmental monitoring for exposure• Sensitive populations
![Page 16: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/16.jpg)
Ecology and Genomics• Human health and model species focus of field
• Ecological data-what can we learn about non-model organisms?
![Page 17: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/17.jpg)
Genomics and Ecology
• More precise measurement than traditional biochemical descriptions of behavior, physiology, population genetics
• Large quantity of data• Comparable among species • Method to detail changes in response to
environment
![Page 18: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/18.jpg)
What is Ecological Risk Assessment?
• A process that evaluates the likelihood that adverse ecological effects may occur as a result of exposure to a stressor.
![Page 19: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/19.jpg)
Planning
• Example Management Goal
–Entity: scallop population in Waquoit Bay, MA
–Attribute: abundance
–Desired State: population that can support a fishery
![Page 20: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/20.jpg)
Genomics and Risk Assessment
PlanningProblem Formulation
Ecological Risk Assessment
Risk Characterization
Ana
lysi
s Characterization of
Exposure Ecological Effects
Communicate Results
Risk Management
As N
eeded: Get D
ata, Iterate, Monitor
![Page 21: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/21.jpg)
Genomics and Ecological Risk Assessments
• Separate exposure and effects of multiple stressors
• Describe effects of toxins-mechanism of action
• Group compounds by mechanism of action
• Measure exposure to and effects of stressors before damage occurs
![Page 22: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/22.jpg)
Traditional Assessment of Environmental Exposure
• Biomarkers of exposure– Peripheral blood levels of hepatic NZ’s or
DNA adducts– Measure tissue toxin level or surrogate
markers• Ecological risk assessments
– Changes in community– Link to stressors after change
![Page 23: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/23.jpg)
Assessment Endpoint
• An explicit expression of the environmental value to be protected
• Measurable entity
• Based on:– Ecological relevance– Susceptibility to a stressor– Relevance to a management goal
![Page 24: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/24.jpg)
Example Assessment Endpoints
• Bird survival
• Eelgrass habitat distribution
• Forest community structure
• Fish survival, growth, reproduction
![Page 25: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/25.jpg)
Types of measures
• Exposure
• Effects
• Ecosystem Receptor Characteristics
![Page 26: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/26.jpg)
As N
eeded: Get D
ata, Iterate, Monitor
Exposure Ecological ResponseAnalysis Analysis
Problem Formulation
Risk Characterization
Stressor-Response
Profile
ExposureProfile
Characterization ofExposure Effects
Measures of Ecosystem andReceptor Characteristics
Measuresof Effects
Measures ofExposure
An
alys
is
![Page 27: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/27.jpg)
Exposure Analysis
• Describe stressor sources
• Describe stressor distribution
• Describe contact or co-occurance
• Prepare exposure profile
![Page 28: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/28.jpg)
Ecological Response Analysis
• Stressor-response analysis
• Establish causality
• Link measures to assessment endpoints
• Prepare stressor-response profile
![Page 29: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/29.jpg)
Linking expression to exposure in vivoXenopus tadpoles
Jelaso et al. 2002
![Page 30: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/30.jpg)
![Page 31: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/31.jpg)
Pimephales promelasCincinnati – NERLDuluth-NHEERL
Fathead minnow
Linking exposure to changes in development and changes in expression
![Page 32: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/32.jpg)
Male fathead minnow
Normal female
Female with male characters(treated with trembolone)
![Page 33: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/33.jpg)
Normal oocyte
Fadrozoletreated oocyte
Pimephales oocytes from fish exposed to Fadrozole
Gary Ankley
![Page 34: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/34.jpg)
Currently only 12 protein- coding DNA sequences available in GenBank
-12S ribosomal RNA-androgen receptor-vitellogenin-P450 aromatase (CYP19)-peroxisome proliferator activated receptor isoform b -P4501A (CYP1A) -P450 17alpha-hydroxylase,17,20-lyase (cyp17 gene)-aromatase-natural resistance associated macrophage protein-G6P1D-glutathione S-transferase-zona pellucida glycoprotein 3
![Page 35: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/35.jpg)
fathead minnow gene homologsStructural18S60S28Salpha-globinmatrix metalloproteinase 9myosin regulatory light chainbeta-actinbeta-globinDesmogleinkeratinlamin B1lamin B2dynein heavy chain
Metabolicdelta-6 fatty acyl desaturaseglucose transporter 1lactate dehydrongenase Imt ATP synthase gamma unitmt cytochrome c oxidase subunit IImt cytochrome c oxidase subunit IIImt cytochrome bmt NADH ubiquinone oxidoreductase subunit 4taurine transporterapolipoproteinITIH2diamine oxidaseNa, K ATPaseadh 3adaUDP-glucose dehydrogenaseGAD 65GAD 67GTPase activating protein
Signal Transduction/Cell Cycle Regulation/TranscriptionMAP kinaseG protein-coupled receptor kinase 7janus kinase 3MAP kinase kinase 6jnk bcreatine kinase 1creatine kinase 2creatine kinase 3mef 2cmef2amyo Dheat shock protein 90 betaK-rasRap1bCyclin A2Cyclin BEF1 alphaEF1 gammaheat shock 90 alphacmosTraf2heat shock factor 2smad 2hexokinaseApoptoticTradd
Neuralpentraxinpresenilin
Developmentalretinol binding proteinfatty acid binding proteinretinoic acid receptor alpharetinoic acid receptor gamma
Immunologicalintegrin beta-2 chainmyeloid proteinC3-Q2C3-H1C3-H2
Endocrineinhibin/activinPit-1estrogen receptor betainsulin receptor 2
Ann Miracle
![Page 36: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/36.jpg)
Sheepshead MinnowCyprinodon variegatus
Well documented life history
Sexually dimorphic
Eurythermal / Euryhaline
Fractional spawners
Primary consumer
Michael HemmerGulf Breeze-NHEERL
Linking in vivo expression data to in situ exposure
![Page 37: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/37.jpg)
Ongoing EPA ResearchField Studies
Adult SHM collected over two years from six sites in Pensacola Bay system
Bayou sites: Texar (urban runoff), Chico (urban, industrial), Grande (Superfund sites)
Male SHM from several locations contained moderate to high levels of plasma Vtg
Courtesy of Michael HemmerNHEERL-Gulf Breeze
![Page 38: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/38.jpg)
Challenges
• Linking gene expression change to toxic endpoint or reproductive endpoint
• Linking changes in gene expression to population or community level effect (ecological risk assessments)
• Lack of genomic information on useful ecological species
![Page 39: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/39.jpg)
Toxicogenomics and ecology: the potential for a canary on a chip
• What is toxicogenomics?
• Applications of genomic data to human health
• Applications to ecological health– EPA research and others
• Applications for toxicology and beyond
![Page 40: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/40.jpg)
Applications for toxicology and
beyond
• Predict community wide effects toxins and other stressors – ecological monitoring
• Interspecies comparisions- sensitive species, competition among species
• Elucidate mechanisms of complex traits
• Identify importance of biological diversity
![Page 41: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/41.jpg)
![Page 42: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/42.jpg)
![Page 43: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/43.jpg)
Phe
noty
pe s
imila
ri ty
Genetic similarity
x
x
x
x
x
xx
x
xx
x
x
x
x
xx
x
Heritability of secondary chemical production in plants
![Page 44: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/44.jpg)
Acipenser fulvescens
![Page 45: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/45.jpg)
Questions for the Great Lakes
• What types of factors are affecting reproduction of sturgeon in the Great Lakes region?
• How similar are sturgeon to model fish species (zebrafish, fathead minnow)?
• Develop a comparable invertebrate model species (Daphnia, Chironomids, Dragonfly)
![Page 46: At the crossroads of genomics and ecology: The potential for a canary on a chip](https://reader038.vdocument.in/reader038/viewer/2022110206/56649cf05503460f949c007b/html5/thumbnails/46.jpg)
Ecological Genomics• Use genomics as a
tool answer ecological questions
• Genomics data as a major part of ecological risk assessment