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Epigenetics
1. Dr Nitika Sobti
Founder – Virtue Baby
Sr. Consultant (Obstetrics and Gynaecology)
Max Super Speciality Hospital
Shalimar Bagh
2. The word epigenetics means
things imposed “on top of
genetics”.
The study of modifications to
DNA that promote changes
in gene expression without
altering the DNA sequence
3.
4. History of Epigenetics
Conrad Waddington coined the term, “epigenetic.
Waddington’s concept was a pivotal concept in
developmental biology as it attempted to explain how a
static set of DNA sequences could dynamically give rise to a
complex organism. Pioneering work by Waddington also
demonstrated compelling evidence for inheritance of a
seemingly acquired characteristic in drosophila fruit flies.
5. Studies
• Johns Hopkins University- First Center for
Comprehensive Study of Epigenetics
• Harvard University -Epigenetic control of gene
expression, epigenetics in mammalian development, and
epigenetics in cancer are few topics from Harvard's
researchers
• The National Cancer Institute of the US - Research areas
include DNA methylation, heterochromatin cancer
pathogenesis, the role of DNA methylation in health and
disease, and tumor phenotypes.
6. Studies
• University of Virginia - topics are the histone code,
chromatin structure, and histone-chromatin crosstalk.
• The University of Cambridge - epigentics in cancer and
other diseases, such as diabetes, Beckwith-Wiedemann
syndrome, and Huntington's disease, and the role of
epigenetics in cells, particularly in mammalian
development.
7. In an article published in Time Magazine in 2010 entitled
“Why Your DNA Isn’t Your Destiny,” the
work of Dr. Lars Olov Bygren, a preventative-specialist and
researcher, is discussed. He discovered that the dietary and
lifestyle conditions affected the genetic expression of not only
the individual, but also their children and grandchildren. He
concludes “it is through epigenetic[s]…that environmental
factors like diet, stress and prenatal nutrition Prenatal nutrition,
Prenatal Stress, Postnatal Behavior can make an imprint on
genes that are passed from one generation to the next.”
GENETICS IS THE HARDWARE & EPIGENETICS IS THE SOFTWARE.
8. Methylation
DNA methylation is an epigenetic mechanism used by cells to control
gene expression. A number of mechanisms exist to control gene
expression in eukaryotes, but DNA methylation is a commonly used
epigenetic signaling tool that can fix genes in the “off” position.
DNA methylation and disease
Researchers are currently looking at the links between DNA methylation
and human diseases such as lupus, cancer, muscular dystrophy and
various congenital defects. Their findings could be significant in aiding
the development of therapies and for understanding and preventing
conditions that develop during embryonic development as a result of
abnormal methylation of the X chromosome and gene imprinting.
9. • The human genome contains 25000-35000
genes as well as switches controlling them.
A genome is a complete set of DNA in a
cell. DNA carries the instruction for
building all the proteins that make each
living creative unique.
• These 25000-35000 genes make only 5%
of genome the rest consisting of switches
(epigenome). As we might say we have a
100 page book & 95 pages are instructions
how to read, the book.
10. From where does this
epigenetic information get laid
on our chromatin-
• Much of it happens during our embryonic development.
• When you were first conceived you were just a group of few
a undifferentiated embryonic stem cells, your chromatin did
not have epigenetic marks/switches on it. It is only when
our cells begin to divide & receive signals & information
from surrounding cells that epigenetic marks begin to
accumulate & genes began to turn on and off. Each cell type
expresses only these genes required for its specific function.
This modification is determined by the interplay between
enzymes which are controlled by epigenetic signal
pathways-that respond to changes in the cell’s local
environment.
11.
12. Perturbations of these signaling pathways can
predisposed to the development of diseases
such as cancer, Alzheimer, Schizophrenia says
Peter Becker (2015) of Ludwig Maximilian
University of Munich.
13.
14. Environmental Genetics
• The early emotional environment can lead to long
lasting epigenetic changes. One example is the
epigenetic changes shown in a special type of mouse
AGOUTI MOUSE.
• Both mice and people have a gene called agouti
(Dolinoy, Huang, & Jirtle, 2007). When a mouse’s
agouti gene is completely unmethylated mouse 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 ones are genetically identical. The fat yellow
mice look different because they have an epigenetic
15. • When pregnant yellow agouti mice were not fed methyl-rich foods,
no folic acid –caused decreased methylation of agouti gene, thus
giving birth to obese yellow mice.
• When pregnant yellow agouti mice were fed methyl-rich foods
(even if they were exposed to chemicals BPA) their offsprings were
brown mice.
• So these genetically identical mice look, so radically different due
to epigenetic changes caused in the womb by pregnant mother’s
diet.
• Our findings provide a framework, charged messages regarding
fear and anxiety also pass modified brain chemistry to their
offspring” (Dias et al, 2015).
16. There is compelling evidence that epigenetic
dysregulation underlines the observed associations
between adult disease and adverse environmental
and nutritional conditions early in development as
suggested in
“Hunger Winter Studies’’ –Baugh principal
researchers, Duke University neurobiologist, stated
that starvation early in life can alter an organism for
generations.
17. Social Epigenetics
• Researchers at the University of Zurich “traumatized” male mice by
separating them from the mother at unpredictable times in the
first two weeks of life.
• The study led by Professor Isabelle Mansuy in 2014 - traumatic
experiences affect metabolism in the long-term and that these
changes are hereditary ( much alterations in the levels of micro
RNA in sperm).
18. Transgenerational Inheritance of Behavioral Traits
• Affectionate maternal care given to female rats pups post natally
results in them giving some quality care to their offspring when
they become mothers. Abusive and neglectful caregivers are
known to leave children particularly susceptible to cognitive and
emotional dysfunction. Indeed, there is a significant association of
reported childhood maltreatment and the later diagnosis of
adolescent and adulthood schizophrenia, borderline personality
disorder, posttraumatic stress disorder, and major depression.
• Higher levels of care-taking behavior during the first week of life
modifies gene transcription throughout the lifespan and promotes
adult behavior that is characterized by stress resilience and
increased maternal care.
19. • Researchers at the University of British Columbia have
demonstrated that human infants of mothers with high levels of
depression and anxiety during the third trimester have increased
methylation of the Nr3c1 gene promoter in cord blood cells
(Devlin, Brain, Austin, & Oberlander, 2010).
• Patrick McGowan found that in suicide victims the levels of
this gene were very low. This gene produces a protein GR-Low
level of this GR receptor is also found in mood disorders,
schizophrenia, and suicide.
• Delivery by elective cesarean section also has shown an increased
risk of certain diseases, such as Asthma, Type 1-diabetes, Obesity,
Celiac Disease, and Cancer.
20. • It is evident from our survey of recent discoveries in epigenetics
how nature (genes) and nurture (the environment) work in
concert.
• The only thing we know for sure is that we are a product of
dynamic interaction between nature and nurture that nothing
about us is written in stone and, therefore, as long as we breathe,
we are a work in progress, constantly changing. Epigenetic
modifications are dynamic and potentially reversible processes.
21. Three simple steps
• Eat plenty of cruciferous vegetable such as broccoli and
cauliflower. They contain antioxidant that enhance our tumor
fighting genes and what way lower our risk of developing cancer.
• Exercise regularly. Exercise has been shown to prevent stem cells
fro turning into fat cells.
• Do not suffer silently of stress, anxiety and depression. They affect
negatively the epigenome. These conditions need to be dealt with
as soon as they arise.
22. Key Take Away
• An individual’s adult health is heavily influenced by early prenatal physiological
factors affecting the mother such as food, pollution, and radiation.
• The unborn child will adjust as best it can to the external environment he/she is
going to encounter upon birth by way of epigenetics changes.
• At least parts of the changed genetics code can be passed on to future
generations.
• Genes don’t make you who you are. Gene expression does. And gene expression
varies depending on the life you live.
• Gene activity cranks up or spins down in response to changes in your
environment.
• Our social lives, our interactions with others and ourselves can change our gene
expression with a rapidity, breadth, and depth previously unknown.