Epigenetics

Question 1

what is epigenetics

Answer 1

heritable modifications of DNA that do not alter the primary sequence, these result in altered gene expression

Question 2

what is the process of DNA methylation

Answer 2

Covalent modification of a methyl group to cytosine at position C5 to make 5-methylcytosine

Question 3

CpG islands

Answer 3

GC rich areas of DNA in their promoter regions

Methylation of the C residues within the CpG islands leads to gene silencing

Question 4

DNA methylation principles

Answer 4

inhibits gene transcription
• Methylation prevents the binding of transcription factors to the promoter and inhibits transcription by converting chromatin from an open to a closed conformation
• Methyl CpG binding proteins contain a methyl binding domain that specifically recognizes methylated CpGs
• Recruits other proteins such as histone deacetylases which remove acetyl groups, favouring compact chromatin

Question 5

Prader-Willi syndrome

Answer 5

– mental retardation
– obesity
- paternal deficiency

Question 6

Angelman syndrome

Answer 6

– mental retardation
– “happy puppet” syndrome
– jerky movements + inappropriate laughter
- maternal deficiency

Question 7

what chromosome causes these abnormalities

Answer 7

Chromosome 15

Inheritance of the wrong “type” of DNA: two from mom or two from dad

Question 8

Heterochromatin

Answer 8

Highly condensed in interphase
Transcriptionally inactive
(contains few genes)
Replicates late in S phase

Question 9

Euchromatin

Answer 9

Organized in 30nm fiber during interphase
Transcriptionally active
Replicates early in S phase

Question 10

position effect

Answer 10

Spreading of heterochromatin
into euchromatic regions causes
cell to cell variability
in gene expression

Question 11

X-chromosome inactivation

Answer 11

Females need to silence one X-chromosome - X-chromosome inactivation

X-inactive-specific-transcript ‘marks’ inactive X:
only expressed from inactive X-chromosome and codes for an RNA (~17kb in humans). No protein product and RNA remains in the nucleus. Followed by DNA methylation.

Question 12

Klinefelter’s syndrome

Answer 12

(where the genotype is 47XXY), the number of Barr bodies would also be 1

Question 13

Rett Syndrome

Answer 13

dominant X-linked, neurodegenerative disorder
Caused by a mutation in the gene encoding Methyl-CpG-binding protein 2 (MeCP2),
which in turn leads to loss of gene silencing at many loci

Question 14

Genomic imprinting

Answer 14

• ~200 imprinted genes on autosomes
• Imprinted genes only expressed from one allele • Dependentonparentalorigin
• Imprinting resets on passage through germline

Question 15

Mechanism of imprinting

Answer 15

• must be somatically available
• must be reversible during gametogenesis
• DNA methylation is the best candidate via epigenetic modification

Question 16

Evidence for imprinting

Answer 16

• Human tumours
– Hydatidiform mole (2 x ♂)
– Ovarian teratoma (2 x ♀)
• Mousechimeras
– Normal + androgenetic  growth enhanced 
– Normal + gynogenetic  growth retarded
• Chromosomeimbalances
– Uniparental disomy

Question 17

Uniparental Disomy

Answer 17

• Both copies of a chromosome are inherited from the same parent
• Individual is missing the chromosome from one of the parents
• Expression altered of imprinted genes on affected chromosome
• Result: chr 15, PWS/ AS
chr 11, Wilms’ tumour

Question 18

uniparental isodisomy

Answer 18

Non-disjunction in meiosis II

Question 19

uniparental heterodisomy

Answer 19

Non-disjunction in meiosis I

Question 20

Tumour suppressor genes are silenced by

Answer 20

DNA methylation in cancer