GEN: Epigenetics Flashcards
what is the central dogma?
where DNA is transcribed into RNA, exported from nucleus to cytoplasm then translated into protein
what is the genome guided by?
epigenome - and Epigenetic factors help regulate gene
expression
what is DNA methylation?
addition of methyl group to cytosine to the fifth carbon of the pyrimidine ring → ie cytosine turns into 5-methyl-cytosine
the hydrogen bond with guanine is UNAFFECTED
what context do cytosines exist in genome?
CpG dinucleotides
where are CpGs found?
clusters called CpG islands
where are these islands unmethylated?
promoter regions
how do methylated CpG compare to other dinucleotides?
methylated in rest of genome but depleted in comparison
how can DNA fit into a nucleus compactly?
winding around nucleosomes with histone protein tails being modified
what are 4 histone modifications?
- acetylation
- methylation
- phosphorylation
- ubiquitylation
Each nucleosome is made of two identical subunits, each of which contains how many histones?
4
H2A, H2B, H3, and H4
what type of modifications do histone proteins undergo?
post translational
what is xist
- Xist is a long noncoding RNA
what is the function of xist?
- Xist initiates DNA methylation &
repressive chromatin process early in
development which spreads across the X chromosome from which it is transcribed
- Dosage compensation of sex chromosomes between females & males is achieved through what?
X-chromosome inactivation
what do histone codes do?
activate or shut down regions of genomes and their genes
what are imprinted genes?
genes expressed from EITHER maternal or paternal alleles (not both)
are imprinted genes dangerous and why?
yes - loss of heterozygosity: gene with no working alleles cannot function!!
→ one silenced copy = greater risk of having no working ones
what are red imprinting disorders?
epigenetic defects: rare genetic disorders, cancers and common diseases
such as:
- silver russell syndrome
- beckwith wiedemann syndrome
- transient neonatal diabetes mellitus
- heart disease
- autoimmune disease
what are uniparental disomies?
two copies part/of a chromosome from one parent and none from other occuring in normal populations
what are two imprinting disorder examples?
- Angelman syndrome
- Prader-Willi syndrome
what causes Angelman syndrome?
mutation in single imprinted gene UBE3A
what causes Prader-Willi syndrome?
loss of function of multiple paternally expressed genes
what are the features of Angelman syndrome?
Happy disposition,
inappropriate laughter,
widely spaced teeth & wide
mouth, stiff, upheld arms
and broad stance and
mental retardation
what are the features of Prader-Willi syndrome?
Typical central obesity,
short stature, small hands
and feet, and mild facial
dysmorphism, PWS patients
are always hungry
what deletion does Angelman and Prader-Willi syndrome share?
cytogenic deletion of chromosome 15q11-13
what is different about Angelman and Prader-Willi syndrome?
Angelman Syndrome transmitted via mother, mutations from father asymptomatic
Prader-Willi syndrome transmitted via father, deletions from mother asymptomatic
what is the cure for Angelman Syndrome?
no cure
what is Beckwith-Wiedemann Syndrome?
human disease with parent-of-origin-associated prenatal overgrowth + cancer predisposition
what chromosome is Beckwith-Wiedemann Syndrome on?
11p15.5
what is Beckwith-Wiedemann Syndrome characterised by?
- large tongue - macroglossia
- large organs - visceromegaly
- large body size - macrosomia
- hernia of the navel
- association with heart failure
when is Beckwith-Wiedemann Syndrome thought to be elevated?
in individuals born following IVF because culturing embryos in plasticware can increase chance of epigenetic problems
what are some Silver-Russel Syndrome characteristics?
- low birthweight
- decreased birth length
- triangular shaped face
- postnatal growth retardation
- poor appetite/reflux
- fifth finger clinodactyly
- normal head size appears large because reduced body length + weight
what chromosomes are affected in Silver-Russel Syndrome
7 and 11 AND DNA methylation at imprinted gene IGF2 - embryonic mitogen
which UPD causes growth failure
- maternal UPD 2/14/16 syndrome → growth failure
which UPD causes drawfism
- paternal UPD 14 syndrome → dwarfism
which UPD causes neonatal diabetes
- paternal UPD 6 syndrome → neonatal diabetes
how is Angelman
syndrome inherited
AS is inherited through the maternal line
AS results from mutations in a maternally expressed gene called UBE3A
