Imprinting Disease Flashcards
What assumptions are made in Medelian Inheritance about each parent’s genetic contribution and expression of parental gene copies?
- Each parents contribution is equal (except for male sex chromosomes)
- Children are expected to express equally (biallelic expression)
What are the symptoms of Prader-Willi Syndrome?
- What causes it?
- Hypotonia
- Poor Feeding
- Develop insatiable appetite during childhood
- Microdeletion in long arm of chromosome 15
What are symptoms of Angelman Syndrome?
- What causes it?
- Spasticity and Seizure
- Severe intellectual disability
- Growth retardation
- Microdeletion in long arm of chromosome 15
What two disease result from deletions on chromosome 15, what explains the different manifestations of this syndrome?
- Prader-Willi and Angelman syndromes
- Manifestations differ on the basis of whether the maternally or paternally derived chromosome is lost.
What are epigenetic Mechanisms?
- DNA modifications that are HERITABLE BUT REVERSIBLE (e.g. X - inactivation in females, gene deactivation through methylation)
Imprinting?
- Small subset of genes where only the paternally or maternally derived genes copy is expressed.
What is the consequence of imprinting?
- Differential (nonequivalent) gene expression that is dependent on parental origin that occurs NORMALLY
What is the master control region of imprinting?
-When does it set the imprint?
Imprinting control region (ICR)
- Imprint set in gametogenesis
In imprinting region if genes are turned on the the sperm, what happens to to egg?
The genes are turned off
T or F: imprinting only happens in only a few genomic locations
False, imprinted genes are located throughout the genome
There are about 150 of them
What is the imprinting cycle?
- Imprint is put into place during gametogenesis (opposite genes will be activated in the sperm and egg)
- That imprint is maintained in the offspring throughout developement and in somatic tissue
- In the gonads the imprint is reset according to the sex of that prospective parent (genes that are not active in the parent may be turned on in the gamete and visa versa to get male specific and female specific gametes)
See 4.1 slide 13
What will happen to all the paternal paterns in a females gametes?
- She will erase them and replace them with a female pattern
What happens if you have a paternally imprinted gene and the maternal gene loses function?
- All gene function at that allele will be eliminated
What is the result of unequal crossing over between LCRs (Low Copy Repeats) in PWS an AS?
It causes deletion of ~5 Mb segment that includes the critical regions
What are PWS and AS and which parental homologues are deleted in each?
- Prader-Willi Syndrome - deletion of paternally-derived chromosome
- Angelman syndrome - deletion of maternally-derived chromosome