Lecture 4: Epigenetic Variation Flashcards
What is epigenetics?
The study of reversible and heritable changes in gene function that occur without altering the sequence
What are the mechanisms of epigenetic change?
Histone Modification and Chromatin Remodelling
DNA Methylation
Non-coding RNA-mediated regulation
Modification of the histone ______ can control the __________ of a gene or the ___________ of chromosomal regions
Tails
Expression
Replication
Are histone modifications heritable? Why/why not?
Yes, DNMT1 follows the replication fork adding methylation marks to newly synthesized DNA reestablishing histone modifications
How does DNA methylation occur?
Occurs at the CpG islands, Methyl group is added to the 5’ C of Cytosine by DNA Methyltransferases (DNMTs)
What enzyme removes Methyl groups from 5-methylcytosine?
DNA Demethylase
Early female embryos have both _____________ active. When the embryo reaches _________, one is chosen to remain active and the other is switched off.
X Chromosomes
~1000cells
How is an X chromosome switched off?
An IncRNA called XIST (X-Inactivation-Specific Transcript) coats the chromosome leading to heterochromatin spreading and an increase in methylation and .’. increases silencing
What is genetic imprinting?
Parent-specific expression or repression of genes and chromosomes in offspring
Which allele is said to be imprinted?
The non-expressed allele
Imprinting diseases are characterised by ____________________.
Non-Mendelian inheritance
What are some examples of imprinting diseases?
- Beckwith–Wiedemann syndrome
- Prader–Willi syndrome
- Angelman syndrome
- Wilms Tumor
- Fragile X syndrome
- Myotonic dystrophy
Loss of imprinting in ____________________ is the most common molecular alteration in human cancer
Insulin-Like Growth Factor 2 (IGF2)
What does an imprinting defect at 15q11-q13 cause?
Prader-Willi and Angelman Syndromes
What is the specific defect that causes Prader-Willi Syndrome?
Deletion of the paternal 15q11-q13
