Genomic Imprinting Flashcards
What is androgenesis and what does it result in in humans?
Ooctye empty of pro-nucleus is fertilised by spermatozoon.
Results in hydatidiform mole. Mostly homozygous 46,XX.
Proliferation of abnormal trophoblast tissue.
Can develop into malignant trophoblastic tumour.
Androgenetic embryos die at 6 somite stage
Well developed extra-embryonic membranes
Poor embryo development
What is parthenogenesis and what does it result in
Abnormal retention of the polar body which results in a 46,XX.
Benign ovarian teratomas
Derived from oocytes which have completed first or both meiotic divisions.
Parthenogenetic embryos die due to failure of development of extraembryonic structures
Trophoblast
Yolk sac
What is genomic imprinting?
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
Give examples of imprinting disorders.
Prader-Willi syndrome
Angelman syndrome
What cytogenetic abnormilities can be found in Prader-Willi and Angelman?
Exactly the same deletion on the long arm of Cr15. In Angelman the chromosome affected is maternal and in Prader-Willi the chromosome affected is paternal.
What is uniparental disomy?
A situation where two homologous chromosomes come from one parent. If both Cr15s are maternal Prader-Willi syndrome will occur.
What distinguishes paternal and maternal dna?
Levels of DNA methylation - high methylation silences genes. If level of methylation remains the same as DNA is transmitted from parent to child the DNA will retain its pattern of expression i.e. ‘memory’. Imprinted genes are usually monoallelic (e.g. one allele has been silenced) and show differences between maternal and paternal copy.
Why did imprinting arise?
Foetal-growth conflict.
More evolutionary advantageous for father genes to promote foetal growth and produce large babies with a an evolutionary advantage.
Better for Mother to restrict foetal growth - large babies increase maternal mortality.
Paternal genes promote foetal growth whereas maternal genes restrict it.
What is Beckwith-Wiedemann syndrome?
Fetal overgrowth High birthweight (>5 kg) \+/- normal adult size Organomegaly Exomphalos Hypoglycaemia Asymmetry Tumour risk Sporadic occurrence (Epi)genetic abnormalities 11p15
What is Russel-Silver syndrome?
Growth retardation Fetal (IUGR) Persistent postnatal growth failure Triangular face Brain size more preserved Asymmetry Sporadic occurrence
What is the mechanism behind the overgrowth/undergrowth syndromes?
Overgrowth - relevant region on maternal Cr11 becomes overly transcribed and starts to behave like paternal Cr11. Promotes growth.
Undergrowth - relevant region on paternal Cr11 becomes methylated and is silenced - i.e. starts to behave like maternal Cr11. Restricts growth.
What is X-inactivation (Lyonisation) and why is it neccessary in females?
Males only have a single dose of X chromosome and Y is mostly heterochromatin. Females require one X chromosome to be silenced in order to receive a normal X dosage. X inactivation occurs randomly in the cells of the early blastocyst.
What is the clinical relevance of X inactivation?
Female who are carriers of X-linked diseases are mosiacs of normal/abnormal cells. This is not always clinically evident.
