Week 8 Flashcards
(73 cards)
What forms a Hydatidiform mole?
46, XX of paternal origin
What are the two ways a hydatidiform mole can form?
Fertilisation of enucleated oocyte by haploid sperm which duplicates
Fertilisation of enucleated oocyte by two sperms
What is Ovarian Teratoma?
46, XX of maternal origin
Parthenogenetic conceptus
What is imprinting?
The remarkable feature od imprinted genes that both active and inactive alleles coexist in the same cell resulting in parental origin monoalllic expression
Maternally expressed = Patnerally imprinted and visa versa
What is biallelic expression?
When both aleles form both parents are expressed
What is an example of maternal suppression and paternal expression?
Maternally methylates promoter of the paternally expressed KCNQ1OT1 ncRNA
Expressive = H3K4me2
Repressive = H3K9me3
How can tissue expression vary between tissues?
Maternal expression of UBE3A is only observed in neurons but is biallelically expressed in all other tissues
Maternal expression of TFPI2 is restricted to the placenta, one of the only tissues expressing the gene
What is the imprinting relationship between mammals?
Imprinting is hightly conserved between mammalians species
Approximately 50% of imprinted genes are conserved between human and mouse
What is the relationship between location of imprinted genes?
Imprnted genes often cluster together.
A single ICR (inmprinting control region) can influence the allelic expression for neighbouring genes, often several 100Kb away
What are the key events in the discovery of imprinting?
Johnson 1974 - hairpin tail allele
Surani et al 1984 - Development of reconstitute mouse eggs
Cattanach and Kirk 1985 - Generated mice with sub-chromosomal maternal duplication
DeChiara et al 1990 - mice inheriting patrnal deletions
What was the work of Johnson 1974?
The hairpin-tail allele (T^hp) presents with a phenotype in heterozygous offspring depending on parental transmission
What was the work of Surani et al 1984?
Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis
What was the work of Cattanach and Kirk 1985?
Generated mice with sub-chromosomal maternal duplications/paternal deficiencies (and the reciprocals), most mouse chromosomes highlighting opposing phenotypes
What was the work of DeChiara et al 1990?
Igf2 imprinting: Heterozygous mice inheriting paternal deletions were small with phenotyoes same as homozygous null. Heterozygous mice inheriting maternal deletions were normal
What is the relationship between gene methylation and gene unmethlyated pre and post fertilisation?
Sperm- Unmethylated Gene A
Oocyte - Methylated Gene A
Blastocyst- Gene A Paternal copy expressed Gene A Maternal copy silenced
What happens to the DNA from sperm after fertilisation?
DNA becomes rapidly unmethylated by the enzyme Tet3 throught the process of active demethylation
What happens to the DNA from the oocyte after fertilisation?
Undergoes a passive demethylation due to the lack of DMNT1 enzyme not copying the methylation, passively dilluting the methylation
Why dont imprinted genes lose methylation?
Two transcription factors bind to the imprinted genes.
The TFs are ZFP57 and DPPA3
How are sex specfic epigenetic coordinated?
Primoridal germ cell goes through a erasure process removing all methylation to then allow for establishment phase to occur selecting sex specific epigenome to be added
What is the time frame of methylation for spermagenesis?
Sperm-derived gDMRs acquired before birth
What is the time frame of methylation for oogenesis?
OOcyte-derived gDMRs acquired after birth
What was the case study of Imprinting may exist due to genetic conflict?
Mice- multiple males per litter
Maternally expressed genes limit growth- higher all survive more equally distrubuted nutrients and lower demand
Paternally expressed genes enhance growth- higher offspring survive
What are the key feaures of X chromosome inactivation?
Only chromosome capable of global silencing
Caused by epigenetics
Model for understanding developmental epigenetics and silencing by non-coding RNAs
Important implication for X-linked diseases
What happens with X chromosome inactivation?
Female embryos transcriptionally silence one of the two X chromosomes. Therefore both females and males express one X chromosome
