Transcript Epigenetic effects can

Trends in Biomedical Science
Epigenetics 1
We will watch a video called “Ghost in Your Genes”
http://www.youtube.com/watch?v=fMxgkSgZoJs
As we watch I will direct you the questions on your
sheets.
Think about these questions.
The transcript of the video can be found at
http://www.pbs.org/wgbh/nova/transcripts/3
413_genes.html
The following notes are from the web site
http://learn.genetics.utah.edu/content/epig
enetics
IDENTICAL TWINS: PINPOINTING
ENVIRONMENTAL IMPACT ON THE
EPIGENOME
Because identical twins develop from a single
zygote, they have the same genome. This
removes genetics as a variable telling scientists
that the differences they observe between the
individuals are caused almost solely by
environmental factors. Recent studies have
shown that many of these environmentally
induced differences are acquired via the
epigenome.
Video
Twinsmovie
http://learn.genetics.utah.edu/content/epigen
etics/twins/
Nature and Nurture
(Genetics and the Environment)
Studying twins helps us to understand how
nature and nurture work together.
For more than 100 years, researchers have
compared characteristics in twins to try to find
more much certain traits are inherited, like eye
color, and which traits are learned from the
environment, such as language.
Twin studies have identified a number of
behavioral traits and diseases that are
likely to have a genetic component, and
others that are more strongly influenced by
the environment.
Data is collected and compared from identical
(monozygotic) or fraternal (dizygotic) twins who
have been raised together or apart. Finding
similarities and differences between these twins
is the start to determining the degree to which
nature and environment play a role in the trait
of interest.
Twin studies have identified some traits that have a
strong genetic component, including reading
disabilities like dyslexia. Other traits, like arthritis,
are more likely influenced by the environment.
Identical twins (left) share all their genes and their home
environment. Fraternal twins (right) also share their
home environment, but only half of their genes. So a
greater similarity between identical twins for a particular
trait compared to fraternal twins provides evidence that
genetic factors play a role
Chromosome 3
pairs in each set of
twins.
One twin's
epigenetic tags are
dyed red and the
other twin's tags
are dyed green.
When red and
green overlap, that
region shows up as
yellow.
The 50-year old
twins have more
epigenetic tags in
different places
than do 3-year-old
twins.
Twin Studies Help Link Environment and
Complex Traits
Because they are genetically the same but
their environments become more unique
as they age, identical twins are a model for
studying how environment and genes
interact. This has become increasingly
important when studying complex
behaviors and diseases.
For example, when only one identical twin
in a pair gets a disease, researchers look
for elements in the twins' environments
that are different. Data is collected and
compared for large numbers of affected
twins and coupled with DNA and gene
product analysis.
These types of twin studies help find the
exact molecular mechanism of a disease
and determine the extent of environmental
influence. Having this information can lead
to the prevention and treatment of
complex diseases.
Eg, for twin pairs where schizophrenia
occurs, in 50% of cases both identical twins
in a pair develop the disease, while only
10-15% of cases in fraternal twins show
this pattern. This is evidence for a strong
genetic component in susceptibility to
schizophrenia. However, the fact that both
identical twins in a pair don't develop the
disease 100% of the time indicates that
there are other factors involved.
Human genome project.
Found approximately 20,000-25,000 genes in
human DNA.
About the same number of genes as fish and
mice.
These few genes didn't seem enough to explain
human complexity.
The same key genes that make a fruitfly, a worm
or a mouse also make a human.
Chimpanzees share 98.9 percent of our genome.
With only a small difference in
chromosomes, how can there be such
a big difference in structure and
function between the species?
Let’s look at a different example.
In this example there seems to be no
difference in the chromosomes, but a
large difference in what happens in
the people.
Angelman syndrome.
Children have a jerky movement when
they're walking. These children have no
speech; they big problems with learning
but are uncharacteristically happy.
The condition is caused by a genetic defect.
A key sequence of DNA is deleted from
chromosome 15.
The Prader-Willi syndrome.
These children are very floppy at birth, but
once they started eating properly, they
then had an big appetite and would get
very, very large.
The condition is caused by the same
deletion in chromosome 15.
??????
The inheritance pattern for the two
conditions showed that:
If the deletion was on the chromosome 15
that the child had inherited from father,
then they have Prader-Willi syndrome,
But if the deletion was inherited from the
mother, they had Angelman syndrome.
How does the chromosome 15 know where it
came from?
There must have been a tag or an imprint placed
on that chromosome, during either egg or
sperm formation in the previous generation, to
say whether it is from the mother or father.
Although the DNA sequence is the same, the
different sets of genes were being silenced
depending on whether it came from the mother
or from the father.
Something other than genes passed
between generations, and could
control genes directly, switch them on
or off.
How?
Video
Epigenome
http://learn.genetics.utah.edu/conte
nt/epigenetics/intro/
Epigenetic effects can:
• change the expression of genes
• be passed from cell to cell, and even
from generation to generation
• don’t involve changes in the DNA
sequence.
NUTRITION AND THE EPIGENOME
Diet is one of the more easily studied, and
understood, environmental factors in epigenetic
change.
The nutrients from food enter metabolic
pathways where they are changed into
molecules the body can use. One such pathway
is responsible for making methyl groups important epigenetic tags that may silence
genes.
Nutrients like folic acid, B vitamins and
SAM-e (S-Adenosyl methionine) are key
components of this methyl-making
pathway.
Diets high in these methyl-donating
nutrients can quickly change gene
expression, especially during early
development when the epigenome is first
being formed.
Nutrients from food are turned into methyl groups along a
pathway: the methyl groups are finally put onto DNA.
Diet During Early Development Can Cause
Changes Lasting Into Adulthood
A mother's diet during pregnancy and what
the child is fed as an infant can cause critical
changes that stay with them into adulthood.
Animal studies have shown that deficiency of
methyl-donating folate or choline during late
fetal or early postnatal development causes
certain regions of the genome to be undermethylated for life.
For adults, a methyl deficient diet still
leads to a decrease in DNA methylation,
but the changes seem to be reversible
with resumption of a normal diet.
Agouti Mice
A mother's diet is important to determine the
epigenome of her offspring.
Both mice and people have a gene called
agouti.
When a mouse's agouti gene is completely
unmethylated it has a yellow coat color, is
obese and prone to diabetes and cancer.
When the agouti gene is methylated (as it is
in normal mice) the coat color is brown and
the mouse has a low disease risk.
Fat yellow mice and skinny brown are
genetically identical.
The fat yellow mice look different because of
epigenetics.
When researchers fed pregnant yellow mice a
methyl-rich diet, most of the resulting pups
were brown and healthy and stayed that way for
life.
These results indicate that an individual's adult
health is heavily influenced by early prenatal
factors.
In other words, health may not only be
determined by what we eat, but also what our
parents ate.
If the agouti gene is switched on all the
time, it blocks a receptor in the satiation
center of the brain.
The satiation center tells mice and us when
we have eaten enough food.
So the yellow animals literally eat
themselves into obesity, diabetes and
cancer.
Toxins and Supplements
Bisphenol A (BPA) is a compound used to
make polycarbonate plastic. It is in many
consumer products including water bottles
and tin cans.
When pregnant yellow agouti mothers were fed
BPA, more yellow, unhealthy babies were born
than normal. Exposure to BPA during early
development had caused decreased methylation
of the agouti gene.
However, when BPA-exposed, pregnant yellow
mice were fed methyl-rich foods, the offspring
were predominantly brown. The maternal
nutrient supplement had counteracted the
negative effects of exposure.
Fathers
Can a father's diet affect the child's
epigenetic outcome?
Scientists studied the well-kept, historical
records of annual harvests from a small
Swedish community.
These records showed that food availability
between the ages of nine and twelve for
the paternal grandfather affected the
lifespan of his grandchildren.
Shortage of food for the grandfather was
associated with extended lifespan of his
grandchildren. Food abundance, on the other
hand, was associated with a greatly shortened
lifespan of the grandchildren. Early death was
the result of either diabetes or heart disease.
Perhaps epigenetic mechanisms are "capturing"
nutritional information about the environment
to pass on to the next generation.
Can We have Nutrigenomics?
As we better understand the connections
between diet and the epigenome, the
opportunity arises for clinical applications.
We may be able to map our gene variations
to help us understand our personalized
medical needs.
We also might be able to profile a person’s
unique epigenome.
Our epigenome may provide information
about how to eat better.
We may be able to look at methylation
patterns and design personalized
nutrition plans.
Nutrient
Food Origin
Epigenetic Role
Methionine
Sesame seeds, brazil nuts,
fish, peppers, spinach
SAM synthesis
Folic Acid
Leafy vegetables,
sunflower seeds,
baker's yeast, liver
Methionine synthesis
Vitamin B12
Meat, liver, shellfish, milk
Methionine synthesis
Vitamin B6
Meats, whole grain
products, vegetables,
nuts
Methionine synthesis
Popular dietary
supplement pill;
unstable in food
Enzymes transfer methyl groups from
SAM directly to the DNA
SAM-e
(SAM)
Choline
Egg yolks, liver, soy, cooked
beef, chicken, veal and
turkey
Methyl donor to SAM
Nutrient
Betaine
Food Origin
Wheat, spinach,
shellfish, and sugar
beets
Epigenetic Role
Break down the toxic byproducts of SAM
synthesis
Resveratrol
Red wine
Removes acetyl groups from histones,
improving health (shown in lab mice)
Genistein
Soy, soy products
Increased methylation, cancer prevention,
unknown mechanism
Sulforaphane
Broccoli
Increased histone acetylation turning on
anti-cancer genes
Butyrate
A compound produced
in the intestine when
dietary fiber is
fermented
Increased histone acetylation turning on
'protective' genes, increased lifespan
(shown in the lab in flies)
Garlic
Increased histone acetylation turning on
anti-cancer genes
Diallyl
sulphide
(DADS)