MCB Lecture 28 Epigenetics II Flashcards
Describe parental imprinting
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
Describe epigenetic reprogramming during gametogenesis, fertilisation and early development
Gametogenesis: all epigenetic marks are wiped
Fertilisation: imprinting is laid down (X inactivation)
Early development: no reprogramming occurs
Only one of the two … is expressed: either … or …
Alleles
Either maternal or paternal
Which … is silenced (… or …) depends on …
Allele
(Mat or pat)
The gender of the parent from which the chromosome came
Describe what is actually happening in parental imprinting in the genome
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
Parentally imprinting genes are mostly found as …
Clusters
How many ICRs does a cluster of genes have?
Just one
What is special about the Kcnq1 locus?
This locus is … Imprinted
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
What sort of methylation happens in the paternal allele of the Kcnq1 locus?
H3K9me and H3K27me
What are the considerations when thinking about imprinting disorders?
Which gene has a mutation?
Did the mutation come from the mum or the dad?
Imprinting disorders are inappropriate expression of …
Imprinted genes
The 15q-11-13 chromosome is … imprinted
Maternally
What are the clinical features of Angelman syndrome
Microencephaly, happy, inappropriate laughter, mental retardation, seizures, puppet like arm movement, hyperactivity
What are the clinical features of Prader-Willi syndrome
Mental retardation Over eating Obesity Small hands and feet Hypergonadism Low muscle tone
What is the cause of Angelman syndrome? (Ie which gene is mutated)
It is the UBE3A gene that is mutated
Mutation in UBE3A causes which syndrome?
Angelman
In which allele is UBE3A expressed?
Thus, mutation in which copy results in Angelman?
Only in the maternal allele
Thus, Angelman syndrome results when the mother gives the child a mutated UBE3A allele
Which two mutations lead to in expression of UBE3A?
i. Direct mutation of UBE3A
ii. Mutation of AS-IC, leading to de methylation of PWS-IC, leading to deactivation of UBE3A
Describe the clinical features of Prader-Willi syndrome
.
Which gene mutation results in PWS?
Is this gene mat or pat expressed?
Mutation in the PWS-IC
The genes in the cluster (normally expressed from the paternal allele) are all lost
What is the result of PWS-IC deletion?
All the paternally expressed genes are lost
The paternal allele now behaves like a maternal allele
Describe the role of Epigenetics in cancer
Hyper methylation of CgP islands
Hypo methylation of the genome
Describe how the tumour suppressing pathway may be deactivated by genetic or epigenetic effects. How do the two differ in an important way?
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
What does genome wide hypo methylation result in? (2)
- Instability
2. Genes turned on
