Imprinting Flashcards
What is imprinting?
Parent of origin effect on gene function
Silencing of genes through epigenetic modifications
What is parthenogenesis?
Virgin birth
What is the result of a gynogenetic zygote?
Almost normal embryo but little/no extraembryonic tissue
What is the result of an androgenetic zygote?
Abnormal embryo but well-developed trophoblast
What structure do two paternal genomes form?
Hydatidiform mole
What structure do two maternal genomes form?
Ovarian teratoma
What is an ovarian teratoma
Result of fusion of two maternal genomes
Usually benign germ cell tumour
What is biallelic expression?
Both maternal and paternal alleles are expressed
Do all chromosomes have imprinted genes?
No
How are imprinted genes distributed?
Roughly even distribution of maternally and paternally expressed genes
Tend to be clustered together
How is Igf2 imprinted?
Maternally-imprinted so paternally-expressed
What is the effect of paternal Igf2 knockout?
Small birth weight
When are epigenetic marks established?
During germ cell development
What kind of epigenetic marks exist?
- DNA methylation
- Histone modifications
- Non-coding RNAs
- Chromatin remodellers
- Higher order chromatin structure
Which base is methylated in DNA methylation?
Cytosine
Which enzymes methylate DNA?
DNMT3 methylates de novo
DNMT1 maintains methylation
What is passive demethylation?
When DNMT1 does not add more methylation during replication
What is active demethylation?
Methylation is actively removed from DNA
What is the histone code?
Histone modifications serve to recruit and bind critical DNA-binding proteins that regulate transcription, replication, recombination and repair
Which gamete is methylated?
Oocyte
Sperm is unmethylated
What occurs to imprinting in the soma?
It is maintained
What occurs to imprinting in the germ cells?
It is erased
Re-established female gametes only
What occurs to maternal imprinting during fertilisation?
Passively demethylated
What occurs to paternal imprinting during fertilisation?
Actively demethylated
How is DNA methylation at imprinting control regions maintained in early development?
Through the imprint-specific factor zfp57
What are the general clinical features of imprinting disorders?
Affect development, growth and metabolism
What is a primary epimutation?
Aberrant methylation of a differentially methylated region in the absence of any DNA sequence change
What is a secondary epimutation?
Aberrant methylation of a differentially methylated region as a result of a DNA mutation in a cis or trans-activating factor
Which genes are Beckwith-Wiedemann syndrome and Silver-Russell syndrome associated with?
11p15
IGF2/CDKN1C affected
What is Beckwith-Wiedemann syndrome?
Gene maternally imprinted and paternally expressed
Syndrome result of paternal disomy
Double dose of IGF2 leads to overgrowth and mental retardation
What is Silver-Russell syndrome?
Gene maternally imprinted and paternally expressed
Syndrome result of maternal disomy
Less IGF2 leads to intrauterine growth restriction
What is Cdkn1c?
Cell cycle inhibitor
Loss in Beckwith-Wiedemann syndrome associated with increased tumour risk
Which genes are Prader-Willi and Angelman syndromes associated with?
15q11 - q13
What causes Angelman syndrome?
Lack of maternal contribution
What causes Prader-Willi syndrome?
Lack of paternal contribution
What is ICR1?
Regulation of an imprinting cluster through a CTCf-dependent boundary
Lacking in paternal allele
What is ICR2?
Regulation of imprinting cluster through non-coding RNA
Lacking in maternal allele
What is the relationship between assisted reproductive technology and imprinting disorders?
3-4 times more likely in ART babies
