An Data Analysis Activity for Students This teacher slide set was created by Dana Haine MS of the UNC Superfund Research Program which is funded by the National Institute of Environmental Health Sciences P42ES005948 ID: 792057
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Slide1
Assessing functional consequences of epigenetic modificationsAn Data Analysis Activity for Students
This teacher slide set was created by Dana Haine, MS, of the UNC Superfund Research Program, which is funded by the National Institute of Environmental Health Sciences (P42ES005948).
Slide2Is there is a relationship between prenatal exposure to arsenic and functional epigenetic changes to newborn DNA ?Does exposure + epigenetic changes = changes to gene expression?
Assessing functional consequences of epigenetic modifications
Slide3Dr. Rebecca FryStudies the link between prenatal exposure to arsenic and cadmium and newborn health.Link to Video describing her research.
Slide4Research Questions in the Fry LabWhat is the relationship between prenatal arsenic exposure and changes to gene expression?Are any of the genes that are altered in association with arsenic controlled by the epigenetic mechanism DNA methylation?
Slide5How were these questions investigated?38 newbornsPrenatal arsenic exposureDNA Methylation ProfilesRNA (Gene expression) Profiles
Slide6Microarray analysis was used to determine which genes exhibited differential expression
The microarray works by first extracting DNA or RNA and hybridizing different pieces representing different genes to a transcriptIt allows us to measure how many copies of each gene is expressed This can tell us whether there is no, some or a lot of RNA transcript present
Slide7334 U-
tAs-associated transcripts
N=38 subjects with range of arsenic exposure, cord blood (vein) isolated
N=224
N=110
A
heatmap
is a way to visualize data trends from microarray
U-tAs
(
µ
g/L)
Slide8Conclusions from Heat MapThere are 334 genes that show a change in transcript profiles in association with arsenic exposure in the 38 babies.Some gene expression profiles increase with increasing arsenic exposure and some gene expression profiles decrease with decreased arsenic exposure
These changes suggest that prenatal arsenic exposure does affect a baby’s gene expression profile
Slide9Are any of the genes whose expression is altered in association with arsenic controlled by DNA methylation?
Slide10The traditional view of DNA methylation
Slide11What would you expect to find?
?
Methylation Level
Level of
g
ene expression
Slide12What would you expect to find?
Slide13What did we see when looking at individual genes?
DNA Methylation
Gene Methylation
RNA Transcript
Gene Expression
Slide14Conclusions2,919 genes exhibited differential methylation in response to arsenic exposure334 gene exhibited corresponding
changes in gene expression (mRNA transcripts)Only 16 genes exhibited a significant linear relationship between methylation and gene expressionSeven of these genes were related to important birth outcomes including gestational age and head circumference
Slide15For most genes, researchers found no correlation between gene expression and methylation
Slide16This pattern is present across the entire genome!