Behavioral Genetics and Epigenetics

2 BROAD categories of behavioral variants

-outside the normal range (medical or psychiatric studies) -within the normal range (individual differences in behavior)

Hypothalamus-Pituitary-Adrenal (HPA)

1. hypothalamus release CRH onto anterior pituitary 2. Anterior Pituitary release ACTH into blood 3. ACTH travels in blood to the adrenal cortex, causes release of glucocorticoids 4. glucocorticoids are steroids that get back into the brain

A single acute environmental exposure during gestation, can actually DIRECTLY expose how many generations?

3 generations

How many SNPs were identified in NR3C1?

4 SNPs

How does this happen?

Alteration in copy number of a gene or genes, copy number variant (CNV), resulting from either a deletion or a duplication might result in abnormal function of genes

Why is GR expression still high in adulthood long after tactile stimulation?

DNA methylation affects gene expression and because methyl marks are stable, DNA methylation can affect gene expression across the lifespan

"Central Dogma"

DNA--RNA--PROTEIN--BEHAVIOR

Methyl marks on the promoter of the DNA make it more difficult for what to be turned on?

GR

high licking and grooming=

HYPO methylation

What does this tell us?

It is something about early life abuse that affected the GR expression -they show increase in methylation (remember-meth=bad)

How can two people with identical DNA be so different?

Many of the same processes of gene regulation that are involved in the normal differentiation of cells and tissues during development are also engaged in adult organism to mediate cellular adaptation to environmental stimuli

Transcriptional Machinery

Multiple molecules bind in the regulatory region of the gene to turn on transcription

What post natal day do differences emerge?

POST NATAL DAY 6

What part determines whether the code will be transcribed?

Promoter

Promoter Region vs. Coding Region

Promoter is like the volume knob, determining how much a gene is expressed Coding region is like a blue print, it contains instructions of how to build protein

Transcription

RNA polymerase begins to move down the strand of DNA and transcribe it into RNA. It unwinds the DNA as it moves down the strans

Transcription factors allow for what?

RNA polymerase to bind to promoter region

Coding Region

Sequence that codes for a protein

What is the HPA axis regulated by?

The Hippocampus

Initiation of Transcription

Transcription factors bind to promotor region

What does deletion or duplication involve?

a rather long region of DNA containing more than one gene

Transcription of a particular gene is initiated when what happens?

a transcription factor binds to the promoter region of the gene. Transcription factors bind directly to DNA sequences and are selective for particular genes

GR expression is downregulated in who?

adult suicide victims that experienced child abuse compared with controls and suicide victims that did not experience child abuse

Loosely packaged chromatin

allows greater access to DNA

Genome-wide association studies

assay SNPs and CNVs across populations

Why are genes "just a part of the story?"

because a variety of genetic and environmental factors are involved in the development of any train -no single gene determines a particular behavior. behaviors are complex traits involving multiple genes that are affected by a variety of other factors.

Genes serve as

blueprints

What activates the HPA?

central nucleus of the amygdala

Variations in the frequency of licking and grooming of rat pups are associated with what changes?

changes in the neural systems that regulate behavioral and HPA responses to stress in adulthood

Acetylation relaxes

chromatin

What is the part of the gene that messenger RNA is transcribed from?

coding region -this region makes up the actual code

Methyl groups are added to what?

cytosines by enzymes called DNA methltranferases

cells

differentiate

So whether chromatin is relaxed or condensed is influenced by

epigenetic marks that attach to the DNA or tails of histone proteins

Methyl groups repress

gene transcription

The hippocampus has one of the highest concentrations of what?

glucocorticoid receptors in the mammalian brain

What do either kind of change lead to?

grossly abnormal function of certain of those genes

Acetylation is reversed by

histonedacetylases or HDACs which remove acetyl groups and compact choromatin

HYPER methylation

impedes transcription: makes it harder to transcribe genes

Behavioral Genetics

individual differences in stress response and stress resiliency

Human Behavioral Genetics

is a relatively new field that seeks to understand both the genetic and environmental contributions to individual variations in human behavior

DNA Methylation

is the type of modification that occurs directly on the DNA sequence

high methylation = (remember meth=bad)

less expression

Offspring of high licking moms have less what and so it is easier to turn on GR gene.

less methylation-easier to turn on GR gene

2 SNPs-association of SNP1 & SNP2 can result in for example what?

major depressive disorder

HYPO methylation

makes it easier for gene to be transcribed

What do added methyl groups do?

makes it more difficult for transcription to occur

low licking/low glucocorticoid receptors=

more CORT being released and less receptors

This context often perpetuated itself so that

multiple generations are affected

Activation of 5H-T receptors leads to activation of what?

of a cyclic AMP-protein Kinase A cascade that induces the expression of the transcription factors

Environmental context affects

offspring development

Histone Acetylation

one type of epigentic mark that seems to be recruited to help drive experience-dependent modifications in cognition and behavior

Genes represent blueprints for

proteins

Generally speaking, behavior is caused by the actions of

proteins -nerve cells -enzymes that produce neurotransmitters or hormones -receptors

Promotor Region

sequence of DNA that transcription facors bind to in order to regulate gene expression

SNP (single nucleotide polymorphism)

small variations in DNA sequences at a single nucleotide base

Epigenetics

stable alterations in how genes are expressed (turned on/off)

Neuroepigenetics

stable changes in gene expression without changes to the actual DNA sequence

Chromosomes are efficient what?

storage units for DNA

The hormone Response is activation of

the HPA Axis

The way the DNA is packaged into the nucleus affects what?

the ability of transcription factors to bind to the DNA and turn genes on/off

Acetylation refers to

the adding of acetyl groups to histone proteins by hirstone acetyltranferases

RNA polymerase

the enzyme that links nucleotides of RNA together in the chain

Genes can only influence

the probability that a particular behavior is expressed

Licking and grooming of pups activates what?

thyroid hormone-dependent increases in hippocampal serotonin levels

Certain marks result in

tighter packaging, which keeps genes inactive, because the trancriptional machinery that turns genes on cant access the DNA

So in a muscle cell, genes that encode liver enzymes are kept

tightly packed and functionally silenced

One well-described neuroendocrine function of the hippocampus is...

to participate in TERMINATING the stress response through glucocorticoid-mediated negative feebback that inhibits the hypothalamus pituitary-adrenal axis (HPA)

Methyl Mark on Cytosine

where methy group are added

Epigenetic marks influence what?

whether chromatin is tightly or loosely packed, which turns gene expression on or off