Genetics - epigenetic responses to diet + stress
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1
Smaller babies = increased risk of...
Metabolic diseases
Obesity
SCZ
Non-insulin dependent diabetes
Obesity
SCZ
Non-insulin dependent diabetes
2
Outline metabolic syndrome
Abdominal obesity
High BP
Impaired fasting glucose
High triglyceride levels
Low HDL cholestrol levels
High BP
Impaired fasting glucose
High triglyceride levels
Low HDL cholestrol levels
3
What does metabolic syndrome increase the risk of?
Diabetes
Heart disease
Stroke
Heart disease
Stroke
4
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5
What is the 'central dogma'?
Information only flows one way
DNA to RNA to protein
or
RNA to protein
DNA to RNA to protein
or
RNA to protein
6
Outline the classical view of inheritance
Acquired characteristics cannot be inherited
Genes have no memory of the environment or experiences of previous generations
Genes have no memory of the environment or experiences of previous generations
7
Define epigenetic changes
Changes in DNA that do not involve alterations to the underlying sequence
Chemical modifications that change the degrees to which genes are turned on and off
Certain epigenetic modifications may be passed on from parent cell to daughter cell during cell division or from one generation to the next
Might occur through histone modifications and non-coding RNAs
Chemical modifications that change the degrees to which genes are turned on and off
Certain epigenetic modifications may be passed on from parent cell to daughter cell during cell division or from one generation to the next
Might occur through histone modifications and non-coding RNAs
8
What might methylation in the promoter region of a gene cause?
Can block transcription factor from binding so the gene cannot be transcribed
9
How might diet affect epigenetic changes?
Found increased IGF2 DMR methylation in individuals prenatally exposed to famine compared to their same-sex sibling
Over-nutrition also affects epigenetic programming
Over-nutrition also affects epigenetic programming
10
Is adaptation more flexible in the matrilineage or patrilineage?
Male germ line due to constant production of gametes
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12
Example of epigenetic changes producing an entirely different phenotype
Bees fed worker jelly = worker bees
Bees fed royal jelly = queen bee
Bees fed royal jelly = queen bee
13
How does early attachment affect stress-sensitivity over the life time?
In favourable family environment: genetics responsible for 40% stress response
In difficult family with 4+ low income, single parent, very young parent, maternal hostility, low education, smoking during pregnancy, low birth weight: environment overrides genetics in advercy (genetics has no effect)
In difficult family with 4+ low income, single parent, very young parent, maternal hostility, low education, smoking during pregnancy, low birth weight: environment overrides genetics in advercy (genetics has no effect)
14
What did Meany find and when?
2005
More attentive rat mothers have less anxious pups
Anxious mice make less attentive mothers
Glucocorticoid receptors in hippocampus mop up cortisol and turn off stress response
Anxious rats have fewer glucocorticoid receptors
Epigenetics found to be involved
With high maternal care, the methyl group for glococorticoid receptor gene is removed so it is no longer methylated
More attentive rat mothers have less anxious pups
Anxious mice make less attentive mothers
Glucocorticoid receptors in hippocampus mop up cortisol and turn off stress response
Anxious rats have fewer glucocorticoid receptors
Epigenetics found to be involved
With high maternal care, the methyl group for glococorticoid receptor gene is removed so it is no longer methylated
15
What is methylation of the glucocorticoid receptor gene promoter associated with in humans?
Childhood abuse
Found in post mortem brain samples
Suggests early life traima affects gene expression in brain
Found in post mortem brain samples
Suggests early life traima affects gene expression in brain
16
What did Perroud find and when?
2014
Mothers pregnant during Rwandan genocide had more methylation of glucocorticoid receptor gene
And so did their children
Mothers pregnant during Rwandan genocide had more methylation of glucocorticoid receptor gene
And so did their children
17
How does a stress in a male rat affect its offspring?
Decreased stress response
Male offspring: delayed learning, more exploratory
Female offspring: impaired learning, reduced methylation in frontal cortex
Paternal stress affects behaviour and DNA methylation in hippocampus of offspring
Male offspring: delayed learning, more exploratory
Female offspring: impaired learning, reduced methylation in frontal cortex
Paternal stress affects behaviour and DNA methylation in hippocampus of offspring
18
How did enrichment of the male rats' environment prior to mating affect its offspring?
Positive effect on methylation, maternal care and pup behaviour
19
What does HPA stand for?
Hypothalamic-Pituitary-Adrenal system
20
Outline the long term consequences of prenatal and postnatal stress
HPA axis disbalance
Behavioural impairments
Neurochemical changes
CNS disorders
Behavioural impairments
Neurochemical changes
CNS disorders
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22
State the short term benefit of acute stress
Fight or flight response
23
Why might natural selection favour more anxious individuals
Hypervigilance useful against threats to survival
However, stress is less useful to humans in the present
However, stress is less useful to humans in the present
24
What did Miller find and when?
2009
Socioeconomic stress may influence the genetic regulation of stress and sensitivity and attachment
Socioeconomic stress may influence the genetic regulation of stress and sensitivity and attachment
25
How might maternal community-level deprivation affects epigenetic processes?
Found to be significantly associated with higher mean methylation across 8 sites, including serotonin transporter gene SLC6A4
26
What did the Italian study into the effect of prenatal maternal COVID on infants find?
COVID related stress during pregnancy associated with SLC6A4 methylation (potential biomarker of early adverse experiences)
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28
What has binge drinking in adolescent rats been found to lead to?
Neuroinflammation
Epigenetic changes leading to...
- Reduced cholinergic, serotonergic, dopaminergic activity
- Decreased cortical thickness
- Decreased nerogenesis
- Altered and reduced dendritic spines
- Amygdala dysregulation
Epigenetic changes leading to...
- Reduced cholinergic, serotonergic, dopaminergic activity
- Decreased cortical thickness
- Decreased nerogenesis
- Altered and reduced dendritic spines
- Amygdala dysregulation
29
6 ways in which parental input might influence epigenetic changes on development
Embryonic development after fertilisation
Oocyte (immature egg cell) development in foetal daughters
Uterine environment - messages from mother to foetus through placenta
Postnatal care
Puberty - interction with hormones
Spermatogenesis prior to fatherhood
Oocyte (immature egg cell) development in foetal daughters
Uterine environment - messages from mother to foetus through placenta
Postnatal care
Puberty - interction with hormones
Spermatogenesis prior to fatherhood
30
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