L14- Genome Imprinting Flashcards
What is parthenogenesis
oocytes which have completed first or both meiotic divisions
No sperm
46, XX
What is Androgenesis
Sperm enters oocyte (oocyte with no DNA) and then sperm divides
46, XX
Hyaditiform mole
-Androgenetic
Complete hydatidiform moles
Mostly homozygous 46,XX
Proliferation of abnormal trophoblast tissue
Can develop into malignant trophoblastic tumour
No (remaining) embryo
Parthenogenesis
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
Parthenogenetic embryos die due to…?
Failure of development of extraembryonic structures
- Trophoblast
- Yolk sac
(paternally expressed genes tend to be growth promoting whereas maternally expressed genes tend to be growth limiting)
Why do Androgenetic embryos die at 6 somite stage
They have Well developed extra-embryonic membranes but Poor embryo development
Concept of genomic imprinting and what is it? (hard one!)
Mothers and fathers somehow “imprint” their genes with a memory of their paternal or maternal origin
A mechanism that ensures the functional non-equivalence of the maternal and paternal genomes
Not encoded in the DNA nucleotide sequence
i.e. epigenetic
Depends on modifications to the genome laid down during gametogenesis
-Spermatogenesis vs. oogenesis
Affects the expression of a small subset of 100-200 genes
Evolutionarily conserved
Clinical consequences
Angelman syndrome
-Facial dysmorphism Prognathism, wide mouth, drooling Smiling/laughing appearance -Mental handicap Microcephaly Absent speech
Seizure disorder
Ataxic, jerky movements
Angelman 1965
“puppet children”
Bower & Jeavons 1967
“happy puppet”
Prader-Willi syndrome
Infantile hypotonia
- Feeding problems
- Gross motor delay
Mental handicap
Male hypogenitalism/cryptorchidism
Small hands and feet
Hyperphagia
-Obesity
Stereotypic behaviour
Cytogenetic abnormalities in Angelman syndrome and Prader-Willi syndrome
Deletion of chromosome 15
Found in both Angelman and Prader-Willi syndromes
Always de novo
-Recurrence risks very low
What is DNA methylation?
Post-synthetic DNA modification
Epigenetic
-Does not normally alter DNA sequence
DNA methyltransferases Reversible Has to be “maintained” after replication Occurs at CG dinucleotides Many promoter regions spared -CG “islands” -Gene regulation
Do Imprinted genes show mono allelic expression?
Yes, Epigenetic differences between maternal and paternal copy (allele)….only one will be activated
IGF2 and Russell-Silver syndrome
Hypomethylation –> decreased IGF2 –> SRS
If IGF maternal and paternal genes are off
One needed to be on for it to be normal
IGF2 and Beckwith-Wiedemann syndrome
Hypermethylation –> increased IGF2 –> BWS
If both maternal and paternal genes for IGF2 are on
One needed to be on for it to be normal
Russell-Silver syndrome
Growth retardation -Fetal (IUGR) -Persistent postnatal growth failure Triangular face -Brain size more preserved Asymmetry Sporadic occurrence
