MCB Lecture 28 Epigenetics II

Question 0

Describe parental imprinting

Answer 0

Different ICRs are imprinted depending on the gender of the parent that the chromosome came from

This means that only one of the two alleles is expressed

Question 1

Describe epigenetic reprogramming during gametogenesis, fertilisation and early development

Answer 1

Gametogenesis: all epigenetic marks are wiped
Fertilisation: imprinting is laid down (X inactivation)
Early development: no reprogramming occurs

Question 2

Only one of the two … is expressed: either … or …

Answer 2

Alleles

Either maternal or paternal

Question 3

Which … is silenced (… or …) depends on …

Answer 3

Allele

(Mat or pat)

The gender of the parent from which the chromosome came

Question 4

Describe what is actually happening in parental imprinting in the genome

Answer 4

A region of DNA called the Imprint Control Region is methylated (H3K9me & H3K27me)

This occurs in different places depending on whether the chromosome came from the mum or the dad

Question 5

Parentally imprinting genes are mostly found as …

Answer 5

Clusters

Question 6

How many ICRs does a cluster of genes have?

Answer 6

Just one

Question 7

What is special about the Kcnq1 locus?

This locus is … Imprinted

Answer 7

Maternally imprinted

This locus produces a long non coding RNA that turns of gene transcription of the genes in the cluster

Since the gene is imprinted and silenced in the maternal copy, only the maternal copies of the genes will be expressed

Question 8

What sort of methylation happens in the paternal allele of the Kcnq1 locus?

Answer 8

H3K9me and H3K27me

Question 9

What are the considerations when thinking about imprinting disorders?

Answer 9

Which gene has a mutation?

Did the mutation come from the mum or the dad?

Question 10

Imprinting disorders are inappropriate expression of …

Answer 10

Imprinted genes

Question 11

The 15q-11-13 chromosome is … imprinted

Answer 11

Maternally

Question 12

What are the clinical features of Angelman syndrome

Answer 12

Microencephaly, happy, inappropriate laughter, mental retardation, seizures, puppet like arm movement, hyperactivity

Question 13

What are the clinical features of Prader-Willi syndrome

Answer 13

Mental retardation
Over eating
Obesity
Small hands and feet
Hypergonadism
Low muscle tone

Question 14

What is the cause of Angelman syndrome? (Ie which gene is mutated)

Answer 14

It is the UBE3A gene that is mutated

Question 15

Mutation in UBE3A causes which syndrome?

Answer 15

Angelman

Question 16

In which allele is UBE3A expressed?

Thus, mutation in which copy results in Angelman?

Answer 16

Only in the maternal allele

Thus, Angelman syndrome results when the mother gives the child a mutated UBE3A allele

Question 17

Which two mutations lead to in expression of UBE3A?

Answer 17

i. Direct mutation of UBE3A

ii. Mutation of AS-IC, leading to de methylation of PWS-IC, leading to deactivation of UBE3A

Question 18

Describe the clinical features of Prader-Willi syndrome

Answer 18

.

Question 19

Which gene mutation results in PWS?

Is this gene mat or pat expressed?

Answer 19

Mutation in the PWS-IC

The genes in the cluster (normally expressed from the paternal allele) are all lost

Question 20

What is the result of PWS-IC deletion?

Answer 20

All the paternally expressed genes are lost

The paternal allele now behaves like a maternal allele

Question 21

Describe the role of Epigenetics in cancer

Answer 21

Hyper methylation of CgP islands

Hypo methylation of the genome

Question 22

Describe how the tumour suppressing pathway may be deactivated by genetic or epigenetic effects. How do the two differ in an important way?

Answer 22

Hyper methylation of the control regions of genes that are involved with tumour suppression

This means that these processes (cell death, senescence) do not occur

Question 23

What does genome wide hypo methylation result in? (2)

Answer 23

1. Instability

2. Genes turned on

Question 24

What mutations lead to cancer causing epigenetic marks?

Answer 24

Mutations in the genes for Histone Methyltransferases

Question 25

What do epigenetic cancer drugs target?

Answer 25

They target enzymes that perform deacetylation

And enzymes that methylated tumour suppressor genes

Question 26

Why are monozygotic twins important for the study of Epigenetics?

Answer 26

Because they are genetically identical, but epigenetically different

Thus we can see the effect of epigenetic modifications

Question 27

Describe Epigenetics in agouti rats

Answer 27

They are genetically identical and are raised in identical environments

However, agouti rats have white fur and will get diabetes.

This is because they lack an epigenetic that turns of the agouti gene

Normal mice have methylation of this gene, and thus they do not express the agouti gene

Question 28

Describe the affect of diet on Epigenetics

Answer 28

The food that a mother eats during pregnancy affects the epigenetic markings that are laid down in her baby, and the baby’s gametes also.

Question 29

Describe the effect of behaviour on Epigenetics

Answer 29

Eg. Licking

Baby mice who are licked have decreased epigenetic marks, leading to less stressed adults due to change in Glucocorticoid receptors

Question 30

What is important about IVF in Epigenetics?

Answer 30

IVF babies can an increased chance of epigenetic erasure

This results in increased incidence of imprinting disorders in IVF babies

Question 31

When does epigenetic erasure occur in IVF babies?

Answer 31

Fertilisation