Epigenetics Flashcards
1
Q
Epigenetic
A
- heritable
- self perpetuating changes
- reversible
- doesn’t affect base sequence
- affect how cells ‘read’ genes (switches)
2
Q
Cancer
A
- may silence tumor suppresor genes or activate oncogenes
- wide hypomethylation common
- hypermethylation of tumor suppressors can silence them and allow uncontrolled division
3
Q
X inactivation
A
- epigenetic
- random silencing of maternal or paternal X chromosome
- heterozygous X linked gene and show mosaic patterns in affected females as differnt X inactivated in different cells
4
Q
Hypohidrotic Ectodermal dysplasia
A
- mutation in EDA gene on X chromosome
- EDA part of signalling path essential for formation of structures like teeth, skin, etc
- heterozygous females show mosaic pattern
5
Q
Tortoiseshell Cats
A
- all female
- black and orange alleles of fur coloration gene reside on X chromosome
- if heterozygous, fur color is dependent on which X is inactivated
- pattern determined by inactivation
6
Q
Agouti Mice
A
- agouti gene
- unmethylated = yellow coat, obese, disease prone
- methylated = brown coat, skinny, disease unlikely
7
Q
Health
A
- epigenetic changes observed throughout cancer
- hypomethylation initiates instability
- methylation decreases as cells age
- involved in type 2 diabetes, obesity, neurodevelopmental disorders
8
Q
Twins
A
- used to study epigenetic changes
- identical base DNA but epigenetic changes
9
Q
Dutch Famine
A
- Hunger Winter in the netherlands caused extreme lack of food
- people concieved during this time have less methyl groups on the insulin like growth factor 2
- more obese/more cardiovascular disease
- children also suffer these effects
- F2 generation have higher body weights in adult offspring of prenatally exposed F1 fathers vs. offspring of unexposed F1
10
Q
Epigenetic Inheritance
A
- to show true inheritance you have to show the effect goes to the fourth generation because potentially 3 generations at the same time could be exposed
- adult, baby, baby gametes
- need to rule out genetic effects/direct exposure possibility
- if conditions change again the effect may be lost
11
Q
Erasure of Methylation
A
- methylation largely erased in primordial germ cells
- converted to hydroxymethylation and diluted out during division
- not all methylation erased, making inheritance possible
- methylation is reinstated after differentiation
12
Q
Imprinting
A
- imprinted genes mean we inherit only one working copy
- depending on the gene it is either maternal or paternal
- other copy epigenetically silenced by methyl groups
- reset during gamete formation
- certain genes always silenced in egg/sperm
- parental allele expression displayed by imprinted genes due to parent of origin specific epigenetic modifications
- gene expressed only from one parental allele
- maintained in somatic lineage and reset in germline lineage
- allele of maternally expressed gene in male will not be expressed in offspring as it is inherited as a paternal allele
13
Q
IGF2
A
- part of cluster on short arm of chromosome 11 undergoing genomic imprinting
- H19 gene also involved in imprinting
- imprinting center 1 controls parent specific genomic imprinting of IGF2 and H19
- on maternal allele IC1 promoter is unmethylated and active
- paternal gene has methylation promoter and unmethylated downstream promoter making antisense lncRNA shutting the gene down
14
Q
DLK1-MEG3
A
- chromosome 14
- non canonical Notch ligand that is a negative regulator of adipocyte differentiation
- maternally expressed genes non coding RNAs
- reciprocal imprinting established by methylation of two differentially methylated regions on the paternal allele
- both ICR are paternally methylated
- MEG3 maternally expressed: produces complex silencing paternal gene
- DLK1 paternally expressed
15
Q
Genetic Conflict Hypothesis
A
- hypothesis to explain the evolution of genetic imprinting
- males father many offspring at low personal cost
- females father one offspring at a time with high personal cost
- imprinted genes often involved in growth and metabolism with parentla favoring larger offspring and maternal favoring smaller
- ensures their genetic material passed on
