Epigenetics

Question 1

what is epigenetics and what does it affect

Answer 1

gene expression states that are stable over rounds of cell division but do not involve changes in the underlying DNA sequence of the organism
developmental potential and multicellular identity
nuclear architecture
transcriptional silencing of repetitive sequences

Question 2

What cells fit the following descriptions and what are its epigenetic status: totipotent, pluripotent, multipotent, unipotent

Answer 2

Totipotent=zygote global DNA demethylation
Pluripotent=IPS cells etc. only active X chromosomes, global repression of differentiation genes by polycomb proteins, promoter hypomethylation
multipotent=adult stem cells X inactivation, repression of lineage-specific genes by polycomb proteins, promoter hypermethylation
Unipotent=differentiated cell types X inactivation, derepression of polycomb silenced lineage genes, promoter hypermethylation

Question 3

what does methyation do to expression

Answer 3

represses expression of genes

Question 4

what kind of epigenetic modifications influence how the DNA is packaged into chromosomes and regulate genome function

Answer 4

sites of attachment, loops and long range interactions
compaction, accessibility of DNA in chromatin
modification of core histones at N-termini
Methylation of DNA at CG dinucleotides

Question 5

What helps methylation and what helps demethylation

Answer 5

Methylation=methyltransferase

demethylation=TET proteins

Question 6

what types off methyltransferases are there and what do they do

Answer 6

Dnmt1-maintenacne methylation of hemi-methylated strands
Dnmt2-tRNA methylase
Dnmt3a&b-de novo methylation (methylation of unmodified DNA during development)
Dnmt3L-oocyte and sperm specific roles. Required to establish imprinting in oocyte

Question 7

What are the two types of methylation-mediated transcriptional repression

Answer 7

Direct inhibition-methylation prevents transcription factor action on promoter->gene not transcribed
Indirect inhibition-repressive chromatin shuts down preventing other factors from coming in and maake the gene active in this region

Question 8

What does the post translational modification of N terminal tails affect

Answer 8

active/silent genes, promoters, enhancers, transcriptional elongation, replication

Question 9

what can the histone code be used for and give examples

Answer 9

predicting regulatory regions
H3k9me3/H3k20me3-heterochromatin and imprinting control regions=parasitic DNA
H3k27me3-polycomb binding, devvelopmentally regulated promoters and enhancers
H3k4me3-active promoters
H3k4me1/H3k27me1-enhancers/regulatory sequences
H3k36me3/H3kxAc-active transportation

Question 10

What doe ENCODE do

Answer 10

shows how different histone marks are in particular region compared to healthy
identification of non traditional diseases causing mutation
identification of long range enhancer mutations and other forms of GWAS

Question 11

what could epigenetic defects cause

Answer 11

cancer, silver Russel syndrome, beckwith wiedermann syndrome, transient neonatal diabetes mellitus, heart disease, autoimmune disease, neurogical+psychiatric

Question 12

what is used for he study of epigenetic control of genome function

Answer 12

chromosome architecture (heterochromatin), silencing of retrotransponons/parasitic elements, sex chromossome dosage compensation, alellic exclusion, environmentally induced strategies in expression, developmental reprogramming, genomic imprinting

Question 13

What happens when genomic imprinting goes wrong

Answer 13

parthenogenote-death because placenta not developed (only maternal)
androgenote-death because embryo doesn’t develop (only paternal)

Question 14

What is genomic imprinting

Answer 14

epigenetic marks are set in the germline, maintained during development and are reversible for re-setting in the next generation
manifests as non Mendelian inheritance, involved in human disease

Question 15

Why could genomic imprinting pose a threat

Answer 15

if gene is maternally/paternally silenced, greater risk of having no working copies

Question 16

What is genomic imprinting involved with

Answer 16

development and growth of embryo and extra embryonic tissues, birth defects and cancer, reproductive technologies that involve cloning

Question 17

What are the types of uniparental disomies and why could it pose a problem

Answer 17

paternal, maternal, partial duplication (translocation of chromosome, right no. chromosomes but small portion at top could be uniparental)
most genes are expressed from both alleles but imprinted genes may only be expressed from one parent so misexpresssed in UPD

Question 18

Give examples of human imprinted genetic disease

Answer 18

prader-willi syndrome
angelman's syndrome
beckwith-wwiedeman ssyndrome
silvver-russel syndrome
albright hereditary osteodystrophy
transient neonatal diabetes

Question 19

What is the difference between prader-wiilli syndrome and angeelman syndrome

Answer 19

Both involve cytogenic deletion of 15q11
PWS-deletion from father, mother asymptomatic, also uniparental disomy of CHr15 (no father=same effect as mutation and deletion). involves loss of function of multiple paternally expressed genes
AS- deletion from mother, father asymptomatic. Associated with mutation of single imprinted gene UBE3A

Question 20

How do the symptoms of Angelman and Prader-willi differ

Answer 20

Angelman-happy disposiition, inappropriate laughter, widely spaced teeth, wide mouth, stiff uphed armss and broad stance, mental retardation
prader-willi-central obesity, short stature, small hands and feet, mild facial dysmorphism, always hungry

Question 21

what does a good diagnostic test for AS and PWS do

Answer 21

Methylation status at the AS/PWS region is diagnosed by 2 methylation-PCR methods for AS and PWS
Methylation identifies patients with a deletion, UPD or imprinting mutation

Question 22

What are common symptoms for Beckwith-Wiedemann syndrome

Answer 22

large tongue, large organs, large body size, hernia of navel, small head, cancer predisposition

Question 23

What is BWS caused by

Answer 23

deregulation of imprinted genes
most cases are sporadic and reult from epimutation at either of the two 11p15.5 imprinting centres (IC1 and IC2)
germline mutations in NLRP2 gene in a familial form of this imprinting disorder

Question 24

What elevates BWS incidence

Answer 24

IVF

Question 25

silver-russel syndrome featuresd

Answer 25

low birth weight, decreased birth length, triangular shaped face, postnatal growth retardation, poor apetitie/reflux, fifth finger clinodactyly, normal head size appearing large because of reduced body length and weight

Question 26

SRS cause

Answer 26

7 sporadic cases have maternal UPD 7. Paternal UPD 7 are normal. SRS exhibits imprinting effect

Question 27

albright’s hereditary osteodystrophy causse

Answer 27

associated with imprinted GNAS locus

Question 28

albright’s hereditary osteodystrophy symptoms

Answer 28

abnormality in end organ (rrenal) response to parathyroid hormone though parathyroid glands itself are normal. Short metacarpals, metatarsalss, phalanges, wide bone, thickening of calvaria.