Week 10 Flashcards
What is imprinting?
The remarkable feature of imprinted genes is that both active and inactive alleles coexist in the same cell resulting in parental of origin monoallelic expression
What are the outcomes for imprinting?
The imprinted allele is the silent one.
Maternally imprinted = Paternally expressed
Paternally imprinted = Maternally expressed
What encodes for silencing of a gene?
Through methylation of promoters
What genome wide imprinting effects occur when they are two male chromosome sets?
Embryo poorly developed
Placenta forms optimally
Yolk sac slightly smaller
What genome wide imprinting effects occur when they are two female chromosome sets?
Embryo developed but slightly smaller
Placenta forms poorly
Yolk sac slightly smaller
What genome wide imprinting effects occur when they are male and female DNA but male is added and removed?
All forms normally
What happens if there are 46 male fertilisation?
Complete hydatidiform mole
Fertilization of enucleated oocyte by haploid sperm which duplicates or fertilization of enucleated oocyte by two sperms
What happens if there are 46 chromosome female fertilisation?
Ovarian Teratoma (or dermoid cyst), 46, XX of maternal origin
Parthenogenetic conceptus
What is an overview of imprinting evolution?
Imprinting is highly conserved between mammalian species and mouse
Approximately 50% of imprinted genes are conserved between human
Not found in reptiles and birds
What is the relationship between gene location between genes that are imprinted?
A single ICR/DMR can influence the allelic expression for neighboring genes, often several 100kb away
What happens to imprinting after fertilisation?
Zygote is demethylated by enzyme Tet3
ZFP57 and DPPA3 keep important embyo imprints present
DNA is remethylated using hemimethylated base
What happens with the imprinting of gametes?
Oocyte imprinting occurs after birth
Sperm imprinting occurs before birth
What is the reason people think imprinting may have evovled?
May exist due to genetic conflict
Maternally expressed genes limit growth
Paternally expressed genes enhance growth
What are examples of male expressed genes and impact when knocked out?
Igf2 K/O mice are growth restricted
Pik3r1 K/O mice are growth restricted
What are examples of female expressed genes and impact when knocked out?
Grb10 K/O mice show over-growth
Igf2r K/O mice show over-growth
What non compatitve reason why imprinting evolved?
Most imprinted ICRs acquire DNA methylation from the oocyte.
Therefore parthenogenetic activation will be prevented in mammals due to the lack of paternally expressed genes.
What is an overview of imprinting syndromes?
There are 11 known imprinting syndromes in humans.
They are associated with genetic changes:
1. Gene mutations
2. Copy-number variants (deletions and duplications)
3. Uniparental disomy
4. Epigenetic errors.
The frequency of the four types of molecular alterations varies between the different syndromes
What is an overview of Silver-Russel syndrome?
Relative macrocephaly at birth, body asymmetary and feeding difficulties
1/75000 people
WHat is an overview of Beckwith-Wiedemann syndrome?
Lateralised overgrowth, hernia of organs
1/15,000
What do Silver-russel and beckwith-weidemann syndrome have in common?
Problems with methylation of H19 gene
SR - Hypomethylation of H19 reducing paternal expression
BW - Hypermethylation of H19 increasing maternal expression
What is an overview of Angelman syndrome?
Severe intellectual disability, laughing and love of water
1/20,000 people
What is an overview of Prader-Willi syndrome?
Intellectual disability, hyperphagia and obesity
1/25,000
What do Angelman syndrome and Prader-Willi syndrome have in common?
Chromosome 15 deletion
AS - Removal of active allele of UBE3A
PWS - Deletion of active allele of MAGEL2 and SNORD116
