Epigenetics & Genomic Imprinting Flashcards
what is epigenetics
gene regulatory mechanisms that do not directly involve DNA sequence
So it involves chromatin structure
how does epigenetics control gene regulatory mechanism
via chromatin structures - euchromatin and heterochromatin
what is euchromatin
open, available for transcription
what is heterochromatin
closed, unavailable for transcription
epigenetic effects can be: (list 4 things)
dynamic
stable through life of a cell
stable through mitosis and be passed onto daughter cells after division
stable through meiosis and be passed from a parent to an offspring
what is an epigenetic mark
modification occuring that controls chromatin structure
can the enviornment affect epigenetic marks
yes
what can lead to obesity regarding this subject
epigenetics - if parents are obese they can change thei way their genes are expressed and passed that to their children
DNA methylation is involved in what
gene silencing
histone modification is what
histone acetylation -activation
histone methylation - variable
ATP-Dependent Chromatin Remodeling - is what
Si/Snf can activetly change the structure, can open or close the chromatin
What are variant histones
Like H2A, H2A.Z, just different histones that have different affects on chromatin structure
dpeneding on which variant is in nucleosome means what
greater propensity for euchromatin or heterochromatin
noncoding RNA h-how do they affect epigenetics
miRNA, siRNA, IncRNA
what is imprinting
one parent has epigeneitc mark that gets inherited by child
what is x chromosome inactivation related to epigenetics
balances gene expression b/w males and females
how does DNA hypermethylation affect cancer
silencing of tumour suppressor and other genes
explain general process that needs to happen to clone mammal
differentiated cell (like skin cell), want to make it pleuripotent, have to erase all the specific epigentic marks and then reestablish epigenetic marks consistent with pluripotent cells
What is SCNT
somatic cell nuclear transfer
what happens to somatic cell nuclear DNA when it gets put into egg cell
it turns pleuripotent
DNA methyltation is an example of what
epigenetic control method
where does DNA methylation happen
on cytosines when they are in CpG sequence
If template strand is methylated what happens to the other coding strand
it is also methylated, it would also have CpG in the other direction
Large amounts of CpG islands means what
high frequency of CGg, hypermethylation and strong silencing
spontaneous deamination of C leads to what
U
Because uracil is not a normal base in DNA what happens
mistmatch repair, it ultimately makes thymine
What is the ulatimate result of spontaneous deamination of C
mismatch repair may happen, which could ultimately change the DNA sequence depending on which strand is repaired
What disease has one of the most frequently mutated bases in the humane genome
Achondroplasia:
when cytosines are methylated it promotes what
heterochromatin structure
What methylate the cyosines
DNA methyltransferases
Once DNA is methylated what binds to methyl groups and binds
methyl-binding domain proteins like MeCP2
CG dinucleotides are underrepresented, why?
because spontaneous deamination of C happens so often, mismatch repair: C → T (deamination of Me-C) and G → A (mismatch repair)
What does DNA hypomethylation do?
activates oncogenes, resulting in chromosome instability & activates transposons
What do mutations at methylated cytosines do?
results in inappropriate gene expression
What do imprinting defects result in?
loss of parental identity
Once DNA becomes methylated, what happens to it
it stays methylated
If DNA is methylated what happens to it once it goes through mitosis
daughter cells will be methylated and it stays methylated
What is the majority of methylation used for
through development as genes are no longer needed they are silenced via methylation
Do primoridal cells have a lot of methylation?
no - very low levels of methylation
describe methylation levels of sperm and egg
sperm has more methyation than egg, they both have higher methylation than primordial germ cells
immediately after fertilization what happens regarding methylation
demethylation until the blastocyst stage
Describe genomic imprinting
alleles inherited from father may always be inactivated or inherited
certain autosomal genes are expressed only from the allele found on the chromosome from a specific parent
What is imprinting mediated by
DNA methylation
the inactive allele inherited from parent is what
imprinted
AD glomus tumors is now called what
Autosomal Dominant Paraganglioma
silently growing, mostly benign tumors of parasympathetic ganglia, usually in the head and neck region is what disease?
AD Paraganglioma
How is AD paraganglioma inherited
only from the father
how is AD paraganglioma imprinted and expressed
maternally imprinted
paternally expressed
the disease only presents if the disease is on which chromosome regarding imprinting
the active chromosome, so the one not imprinted
What does BWS stand for
Beckwith-Weidman Syndrome
What is MOI of BWS
AD
How is BWS imprinted and expressed
paternally imprinted, maternally expressed
Overgrowth syndrome, infants larger than normal, growth asymmetric is what disease
BWS
How is BWS inherited
from mother
Why does imprinting happen?
They THINK:
it has somethign to do with limiting an allele for the function of a gene
Describe monoallelic vs. biallelic expression
most genes are biallelic expression
when imprinting happens the allele is monoallelic expressed
a defect in imprinting will lead to what
developmental problems
if imprinting doesn’t work what will happent o parent of origin affect
there will be no parent of origin affect
if there is a mutation on an imprinted gene, what will be phenotype
no phenotype, imprinted is not expressed, the only way it would have phenotype if its on chromosome that is exprsesed
most of the time impritning affects all cells in body, sometimes it is:
cell-type specific
what happens to imprinted genes during gametogenesis
they are reset
explain resetting imprints
during spermatogenesis or oogenesis, the imprints are reset so that a sperm would only have male specific imprints and female would only have female specific imprinting patterns
If during spermatogeneiss a gene is mutated that is paternally imprinted, what is result
it will be hidden b/c if it’s from father it is imprinted (off)
What does PWS stand for
parader-willi syndrome
What chromosome is affected in AS
15q11-13
what does AS stand for
angelman syndrome
What is the most important gene in AS
UBE3A
The contribution of what leads to AS
lack of maternal contribution
What is UBE3A
important in brain
brain-specific ubiquitin ligase
severe intellectual disability, seizures, happy demeanor, lack of speech is what disease
AS
poor feeding when born, hyperphagia and obesity, hypopigmentation, mental retardation is what disease
prader-willi syndrome
the contribution of what leads to PWS
lack of paternal contribution
what chromosome is important in PWS
15q11-13
What important genes are involved in pWS
SNRPN
sometimes OCA2
What is SNRPN involved in
assembly of SnoRNA
SNRPN - how is it usually inherited
paternally expressed, maternally imprinted
UBE3A - how is it usually inherited
maternally expressed, paternally imprinted
If one allele is turned off by imprinting and the other allele carries loss of function mutation, what happens
disease will present
what is uniparental disomy (UPD)
two chromosomes from same parent
go over mechanisms on the basis of PWS & AS
pg 42
how does trisomy occur
via meiotic nondisjunction
what happens if there is mitotic nondisjunction
tetrasomic and disomic daughter cells
if there is mitotic nondisjunction, what will happen to tetrasomic cells
they will die- only the disomic cells will develop into baby
what is the danger in mitotic nondisjunction
if there is unequal passing of maternal/paternal alleles via the mitotic nondisjunction
what is the chance a child will have uniparental disomy if there is mitotic nondisjunction
1/3
what is chance a child will be normal if there is mitotic nondisjunction
2/3
what is idiosomy
resulting cell will have both alleles from same parent
when does idiosomy occur
through disomic amete from non-disjunction in meiosis II
what is a danger phenotypically with idiosomy
if the allele inherited carried recessive allele, the child could have AR disease
What is heterodisomy
two different alleles but both from same parent - baby only has contribution from one parent
how do you diagnose PWS or AS
southern blot
what is the probe for PWS or AS when doing southern blot
SNRPN probe
Why is NotI used to detect PWS
to detect the allele being expressed
How does NotI work?
will not cut methylated DNA (imprinted) but will cut non-methylated DNA - so it only cuts what is expressed
Are genes inherently paternal or maternal?
no
what do imprinting patterns refer to when we say they are paternal or maternal
if they most recently came from sperm or egg - for example the father could pass on a paternal imprint allele that he got from his mother.
How does Xbal work?
restriction enzyme that cuts either allele, it isn’t sensitive to methylation
Where is mutation in Albinism Type 2
OCA2
What is MOI of Albinism Type 2
AR
OCA2 gene for albinism is in same region as what
SNRPM - (in same region that both angelman and PWS is)
