Download Prenatal Arsenic Exposure and Altered Gene Expression

Gene Expression and
Epigenetic Regulation
JESSICA LAINE AND ELIZABETH MARTIN
The Central Dogma of
Biology
How does the cell control
these processes?
Research Questions in the
Fry Lab

What 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?
How were these questions
investigated?

38 newborns
 Arsenic
exposure
 DNA
Methylation
Profiles
 RNA
(Gene
expression)
Profiles
Is there is a relationship between
prenatal exposure to arsenic and
functional epigenetic changes to
newborn DNA ?
Microarray 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 transcript

It allows us to measure how
many copies of each gene is
expressed (i.e. has transcript)

This can tell us whether there
is no, some or a lot of RNA
transcript in the cell
What is a heatmap and
how do you read it?
Lower iAs
Higher iAs
?
?
?
?
334 U-tAs-associated transcripts
U-tAs
(µg/L)
A heatmap is a way to
visualize data trends
N=224
N=110
•
•
N=38 subjects with range of arsenic exposure, cord blood (vein)
isolated
Multi-variable models for association between arsenic
exposure-prenatal and gene expression
Conclusions

There are 334 genes that show a change in
transcript profiles in association with arsenic
exposure in the 38 babies in the BEAR cohort

There are gene that expression changes in
both a positive and negative way: some
genes 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’sgene
expression profile
Are any of the genes
that are altered in
association with arsenic
controlled by the
epigenetic mechanism
DNA methylation?
The traditional view of
DNA methylation
What would you expect
to find?
What did we see when
looking at individual genes?
What did we see when
looking at individual genes?
RNA Transcript
Gene Expression
DNA Methylation
Gene Methylation
Where do these
measurements come from?
What conclusions can we
draw from this?

Methylation does indeed control
for some genes’ gene expression, in
this study we found 16 genes were
controlled by gene expression

Some of these genes were related
to important birth outcome
including gestational age and
head circumference
Questions?
What did the researchers
actually find?
This pattern is present
across the entire genome!