1. Nature vs. Nurture

2.  Once nurture seemed clearly distinct from nature. Now it
appears that our diets and lifestyles can change the
expression of our genes. How? By influencing a network of
chemical switches within our cells collectively known as
the epigenome.
 This new understanding may lead us to potent new
medical therapies.
 Epigenetic cancer therapy, for one, already seems to be
yielding promising results.
 Epigenetic treatment of mental illness is just around the
corner.

3. An Epigenome consists of a record of the
chemical changes to the DNA and
histone proteins of an organism.
These changes can be passed down to an
organism's offspring.

4.  For the most part, every cell in our body
contains exactly the same genes, but inside
the individual cells some genes are activated
while others are silenced.
 When genes are active they are capable of
being translated into proteins. When genes
are silent, they are inaccessible for translation
into proteins.

5.  Some genes, like the Foxp2 gene, are only turned on during
the early months of human development and then silenced
via epigenetic mechanisms.
For example the Foxp2 gene
controls the wiring of the speech
areas in the developing brain.
Mutations in the FOXp2 gene
cause developmental verbal
dyspraxia. These individuals have
no developmental delays, but are
unable to perform the coordinated
movements required for speech.

6.  Epigenomics is the science of activating or silencing genes at
the level of transcription or translation.

7.  Genes can be activated or silenced :
-By modifying the histone proteins (H3 or H4)
-By modifying the DNA (methylation at CpG promoters)
-By small interfering RNAs
According to some also
-By genomic imprinting

8. Histones are DNA
binding proteins
that act as spools
that keep the DNA in
coils.

9. Histone 3 and 4 can be
modified by methylation.

10. Methylation keeps the histones tight together. In this state the DNA
cannot be transcribed/expressed. In order to be transcribed and
expressed the histones must come apart by either demethylation or
acetilation.

11. Fragile X Syndrome is caused by an expanded CGG trinucleotide
repeat in the Fragile X Mental Retardation (FMR1) gene leading to
epigenetic silencing (by methylation) and loss of expression of the
Fragile X Mental Retardation Protein (FMRP).

12.  Normal FMRP is present on everyone’s X chromosome.
 It plays a role in:
Synaptic protein synthesis
Synaptic plasticity
Dendritic spine formation
Neuronal plasticity
In fragile X syndrome the
FMRP is not expressed, thus
nonexistent.
Fragile X Syndrome is an X-linked
condition associated with
intellectual disability,
hyperactivity, attention deficits,
anxiety and autistic-like behaviors.

13. RNA interference - gene silencing by small non-coding RNAs.
The non-coding
RNAs interfere
with protein
synthesis
machinery of
the cell,
silencing a
gene.

14. Huntington’s disease is a result of what is called an expanded “triplet
repeat” in the huntingtin gene sequence.
RNA Interference technique could epigenetically silence the mutated
gene, thus eliminating the translation of the CAG triplet repeat.

15.  Genetic Imprinting - For some genes, only one copy is
expressed and the other one silenced, depending on whether
the gene is maternal (comes from the mother) or paternal
(comes from the father).
 Normal development requires one copy of certain genes from
each parent.
 Imprinting does not occur on every chromosome; only nine
chromosomes are known to have regions of genes that are
imprinted.
 Imprinting occurs by a pattern of methylation, meaning the
copy of the gene to be inactivated is coated with methyl
groups.
 Imprinting takes place before fertilization, in the egg and
sperm cells.

17.  Prader- Willi and Angelman syndromes are uniparental disomies
(both copies of the genes on chromosome 15 come from the same
parent).
 Chromosome 15 regulates numerous neurologic and
musculoskeletal structures and functions that affect intelligence,
cognition, behavior, emotion, muscle tone, and metabolism.
 When both copies of chromosome 15 are maternal (called paternal
deletion), genetic imprinting produces a constellation of symptoms
known as Prader-Willi syndrome.
 When both copies of chromosome 15 are paternal (called maternal
deletion), genetic imprinting produces a constellation of symptoms
known as Angelman syndrome.

18.  Mitochondrial DNA (mtDNA) is not wrapped around histone
proteins. For this reason methylation or acethylation does not
influence transcription.
 Mitochondrial DNA does not contain introns which means that
each one of its13 genes is translated into a protein.
HOWEVER:
The mitochondrion contains about 1200 proteins, thus the
remainder of the mitochondrial proteins are encoded by the
nuclear DNA and thus subject to epigenetic factors.

19. Mitochondria encoded proteins are not subject to epigenetic factors, but
proteins encoded in the nuclear DNA (nDNA) are.

20. It is believed that early life stress can alter the epigenome and program
some brain circuits, by making them vulnerabile to major psychiatric
conditions.

21.  Identical twin studies show a schizophrenia concordance rate of 48-60%.
 If schizophrenia were a genetic disorder the concordance rate should be
100% .

22. The first systematic Genom- Wide DNA methylation study
was published in September 2011 in Human Molecular
Genetics.
 This study showed that identical twins discordant for
schizophrenia had a different metylation pattern.
 The twins with schizophrenia presented with a
hypometylated promoter in a specific locus on
chromosome 17 as compared with the unaffected twin.
 This explains why identical twins are not 100% concordant
for schizophrenia.
 (Human Molecular Genetics, Sept.9,2011. Epigenetic Clue To Schizophrenia & Bipolar Disorder).