Genetic Imprinting Flashcards
What is genetic imprinting and how is it achieved?
Genetic imprinting is sex-dependent epigenetic modulation.
It is achieved through methylation of CpG repeats in the silenced gene region.
Define “epigenetics”.
Mitotically and meiotically heritable variations in gene expression that are not caused by changes in DNA sequence
What enzymes act on methylated CpG to silence gene expression?
MeCP2 binds to the methylated CpG
HDAC, SWI/SNF, SIN3, HMT also involved, modify chromatin
Three mechanisms of gene silencing via methylation/MeCP2 complex action.
Compacted chromatin
Hypoacetylated histones
Transcriptional repression
What percentage of genes in the human genome are imprinted?
~1%
Rare for a gene to be imprinted, but common for any individual to have imprinted genes.
In what cells are DNA methylation marks first established?
Gametes
Why is DNA methylation reversible?
DNA methylation must be reset during gametogenesis so the proper sex-specific imprint will be transmitted to progeny.
What enzyme propagates epigenetic marks in dividing somatic cells?
Maintenance methyltransferase
Acts on hemi-methylated replicated DNA
Why is erasure and resetting of methylation patterns during gametogenesis essential?
It ensures that all of the genes transmitted by gametes are properly imprinted. Without resetting, 50% of one parent’s genes would be male imprinted and 50% female imprinted, and offspring would inherit some doubly imprinted and some doubly expressed genes.
What to Prader-Willi syndrome and Angelman syndrome have in common?
The both result from the same chromosomal deletion.
del(15q11-q13)
Prader-Willi = Paternal deletion
Angelman = Maternal deletion
How does Angelman syndrome most commonly arise and what gene is involved?
Angelman syndrome occurs through imprinting of the UBE3A gene on the father’s chromosome 15 and deletion of the 15q11-q13 region on the mother’s chromosome. UBE3A is normally transcribed from the mother’s chromosome.
How does Prader-Willi syndrome most commonly arise and what gene is involved?
Prader-Willi syndrome occurs due to imprinting of the SNORD116 gene on the mother’s chromosome and a 15q11-q13 deletion on the father’s chromosome. SNORD116 is normally transcribed from the father’s chromosome.
Why is uniparental disomy a relatively common cause of Prader-Willi syndrome, but not of Angelman syndrome?
Uniparental disomy is much more likely to occur as a result of nondisjunction events in females than in men. Thus, a zygote that receives both of its copies of chromosome 15 from the mother will lack the un-imprinted SNORD116 it would normally receive from the father. A zygote is much less likely to receive 2 paternal copies of chrom 15.
