14. Epigenetic Inheritance & Imprinting Flashcards
epigenome
range of modifications that are imposed on the genome and ensure the stable transmission of gene expression patterns without changes to the DNA sequence
epigenetics
information passed from one generation to the next but not encoded in DNA
epigenetic disruptor
chemicals, toxins, or environmental compounds that can cause disruptions to epigenome
epimutation
mutations in the epigenome that result in incorrect imprinting or passage
methylation
common alteration in vertebrates that causes a cytosine (in a CG sequence) to be methylated, creating a 5-methylcytosine
is passed on during DNA replication
maintenance methyltransferases
will recognize methylation patterns & make sure after DNA replication that new strands are properly methylated
contributes to stability of gene repression, also called epigenetic silencing
housekeeping genes
associated by GC rich areas (GC islands)
that are maintained on active genes and non-methylated
what happens to methylated CG sequences?
they are selectively lost due to deamination of 5-methylcytosine converting it to thymidine & therefore changing the opposite strand base pair to an adenine instead of the original guanine
what does DNA imprinting do in terms of variation?
increases variation
genetic conflict hypothesis
states that male & female evolutionary goals are different in terms of reproduction
males want large offspring
females want smaller offspring (less physiologically taxing)
example of an imprinted gene?
insulin growth factor 2
insulin growth factor 2 parental genes
mom: IGF2 receptor ON; IGF2 OFF
dad: IGF2 receptor OFF; IGF2 ON
delete mother’s IGF2 receptor gene?
father’s receptor gene on
results in large offspring
delete father’s growth factor gene?
mother’s growth factor gene on
dwarf offspring produced
deleting mother’s IGF2 receptor gene and father’s IGF2 gene results in?
normal sized offspring
epimutation examples (4)
- prader-willi
- anglemanns
- beckwith-wiedemann
- NOEY2
prader-willi syndrome
paternal inheritance of deletion
characterized by hypotonia, obesity, & hypogonadism
angelmann
maternal inheritance of deletion
characterized by epilepsy, tremors, perpetually smiling facial expression
beckwith-wiedemann syndrome
overgrowth disorder present at birth and characterized by increased risk of cancer & congenital features
NOEY2
ras-like paternally expressed imprinted gene on chromosome 1 tumor suppressor for breast & ovarian cancer
by losing expression of this gene, you have an increased risk of these cancers
can be caused in rare cases when both copies of the gene are inherited from the mother (uniparental disomy)
rat epigenetic study: high fat diet (HFD)
significant weight gain
increased leptin & insulin
insulin resistance
rat epigenetic study: paternal high fat diet (HFD)
alters female offspring expression of 77 genes
I1132ra2 was upregulated
reduced methylation–>overexpression
rat epigenetic study: undernourished diet
rats show changes in promoter methylation & gene expression
results in undermethylation & overexpression of PPAR-alpha (increased production of ketone bodies)
increase GC receptors
undernourished female rats produced offspring that were…?
more likely to be overweight
in vitro fertilization
greater risk of low birth weight, birth defects, disorders associated w/lower mean methylation in placental sites & higher mean methylation in cord blood
trans-epigenetic signals
when a gene expresses a product that has positive feedback on the gene itself and is transmitted by a partition of cytosol with a positive feedback loop
example of trans-epigenetic signals
protein product that enhances the gene activity
cis-epigenetic signals
when a gene product alters DNA inherited via chromosome segregation during cell division
cis-epigenetic signals example
product plays a role in histone modification
conformational change to aggregated state example
prions can survive replication in aggregation state (misfolded protein) and will also be inherited
what can explain why identical twins or cloned animals are not exactly the same or the rising obesity rates?
epigenetics
x-chromosome inactivation
(barr body)
because females have 2 X chromosomes, various techniques are used to express that same amount of transcription as males (DOSAGE COMPENSATION)
how is dosage compensation achieved in mammals?
by inactivating one of the two chromosomes in all somatic cells
chromosome that is inactivated is coated with Polycomb complex to help silence expression
non-mammal examples of dosage compensation
- drosophila (genes on male X chromosome expressed at 2-fold levels)
- nematodes: genes on hermaphrodite’s 2 X chromosomes are expressed at half the levels of the male
