Genomic imprinting

Question 1

What happens when 2 parents are not involved in mammalian development?

Answer 1

• Androgenesis

- Parthenogenesis

Question 2

What is a Hydatidiform mole?

Answer 2

-Androgenetic
–Mostly homozygous 46,XX
–Proliferation of abnormal trophoblast tissue
–Can develop into malignant trophoblastic tumour
-No (remaining) embryo

Question 3

Give an example of parthenogenesis

Answer 3

•Benign ovarian teratomas
•Derived from oocytes which have completed first or both meiotic divisions
–Diploid
–Wide spectrum of tissues
–Predominantly epithelial
–No skeletal muscle
–No membranes/placenta

Question 4

Why do uniparental conceptions fail?

Answer 4

-Different roles of maternal and paternal genes
Concept of genomic imprinting
–Mothers and fathers somehow “imprint” their genes with a memory of their paternal or maternal origin

Question 5

What is genetic imprinting?

Answer 5

• A mechanism that ensures the functional non-equivalence of the maternal and paternal genomes
• Not encoded in the DNA nucleotide sequence
• Depends on modifications to the genome laid down during gametogenesis

Question 6

Describe Angelman syndrome

Answer 6

•Facial dysmorphism (Prognathism, wide mouth, drooling, Smiling/laughing appearance)
•Mental handicap (Microcephaly, Absent speech)
•Seizure disorder
•Ataxic, jerky movements
-Puppets

Question 7

Describe Prada-Willi syndrome

Answer 7

Infantile hypotonia (Feeding problems, Gross motor delay)
•Mental handicap
•Male hypogenitalism/cryptorchidism
•Small hands and feet
•Hyperphagia (Obesity)
•Stereotypic behaviour

Question 8

What are the cytogenetic abnormalities in Prada-Willi and Angleman Syndrome

Answer 8

• Deletion of Chromosome 15

- Always de Novo

Question 9

What are the molecular mechanisms in Prada-Willi syndrome?

Answer 9

Lack of paternal 15q11-13 contribution

Question 10

What are the molecular mechanisms in Angleman Syndrome?

Answer 10

• UPD
• Point mutation
• Deletion

Question 11

Describe DNA methylation

Answer 11

• Post synthetic DNA modification
• Epigenetic (doesn’t normally alter DNA sequence)
• Reversible
• DNA methyltransferases
• maintained after replication
• Occurs at CG dinucleotides (islands)
• Imprinted genes show monoallelic expression
• Other chromatin structure differences between expressed and non-expressed allele

Question 12

Describe Russell-Silver syndrome

Answer 12

• Growth retardation (Foetal (IUGR), Persistent postnatal growth failure)
• Triangular face (brain size more preserved)
• Asymmetry
• sporadic

Question 13

When does x-inactivation occur?

Answer 13

When there is a small number of precursor cells

For carriers of X-linked mutations this affects clinical expression

Question 14

What are consequences of X-inactivation (for females)?

Answer 14

-Females are epigenetic mosaics
-Composed of patches of cells working on one X chromosome or the other
-Carriers of X-linked mutations function on some normal cells and some faulty clls
-

Question 15

What are consequences of functional mosaicism?

Answer 15

May be unpredictable and disease specific