Genet 302 lec 41 & 42
What is genomic imprinting?
When the expression of a gene depends on whether it came from the mother or the father
What molecular mechanism is central to genomic imprinting?
DNA methylation
When are imprinting marks established?
During either oogenesis or spermatogenesis
What type of DNA methyltransferase establishes imprinting marks?
De novo DNMTs
Do maintenance DNMTs establish new imprinting marks?
No, they maintain existing methylation
What is the key idea of imprinting after fertilization?
The zygote has both maternal and paternal chromosomes, but some regions keep parent-specific methylation patterns
How can DNA methylation regulate imprinted genes?
It can turn genes off or on depending on where methylation blocks binding of positive or negative transcription factors
Where do imprinting effects usually occur?
At imprinting control regions, or ICRs- this is what gets methylated not the gene itseld
What are imprinted gene clusters?
Groups of about 2 to 12 genes regulated together by an ICR
Are the individual genes themselves necessarily methylated in the lecture model?
No, the key methylation is at the ICR
Why was gene B not imprinted in the example?
Because it was expressed from both parental chromosomes
How long are imprinting methylation marks maintained?
Until gametogenesis
When are old imprinting marks removed?
Before meiosis during gametogenesis
Why must imprinting marks be erased and reset in each generation?
So a person can make gametes with the correct sex-specific imprinting pattern for their own sex
About what fraction of placental mammal genes are imprinted?
About 1%
About how many genes are imprinted in mice according to the lecture?
About 140
What is biparental disomy?
The normal situation where one chromosome copy comes from each parent
What is monosomy?
Having only one copy of a chromosome
Why is monosomy usually nonviable?
Because of gene imbalance from missing one chromosome copy
What is trisomy?
Having three copies of a chromosome
Why is trisomy detrimental?
Because of gene imbalance
What is uniparental disomy, or UPD?
Having both copies of a chromosome from one parent
Does UPD still give two copies of each gene?
Yes
What are the common types of UPD?
Maternal heterodisomy, maternal isodisomy, paternal heterodisomy, and paternal isodisomy
What is heterodisomy?
Two different homologs from the same parent
What is isodisomy?
Two copies of the same homolog from one parent
What is maternal heterodisomy?
Two different maternal homologs and no paternal homolog
What is paternal isodisomy?
Two identical copies of a paternal homolog
What common cause of UPD starts with a trisomic zygote?
Trisomy rescue
How can trisomy rescue produce UPD?
If the chromosome from one parent is lost, the two chromosomes from the other parent remain
What type of UPD can trisomy rescue commonly produce in the lecture example?
Heterodisomy
What common cause of UPD starts with a monosomic zygote?
Monosomy rescue
How can monosomy rescue produce UPD?
The single chromosome is duplicated, giving two copies from one parent
What type of UPD does monosomy rescue commonly produce?
Isodisomy
What is one medical significance of UPD involving recessive mutations?
UPD can make a child homozygous for a recessive mutation
Which type of UPD is especially good at uncovering a recessive mutation?
Isodisomy
Why is isodisomy more likely than heterodisomy to uncover a recessive mutation?
Because it duplicates the same chromosome, making the child homozygous
What is one medical significance of UPD involving imprinting?
UPD can remove the normally required maternal or paternal imprinted gene expression pattern
If a gene is paternally expressed, which UPD types can cause disease by removing paternal contribution?
Maternal isodisomy or maternal heterodisomy
If a gene is maternally expressed, which UPD types can cause disease by removing maternal contribution?
Paternal isodisomy or paternal heterodisomy