Imprinting and Epigenetics - RS Flashcards
How do Prader-willi syndrome (PWS) and Angelman syndrome (AS) appear on karyotype?
They both appear to have the same deletion on the proximal interstitial long arm of chromosome 15
How do PWS and AS appear on FISH?
both look the same and cannot be distinguished.
For Prader-Will syndrome (PWS) patients is it the maternal or paternal chromosome 15 that has the deletion?
The paternal chromosome (the parent isn’t always afflicted)
For Angelman Syndrome (AS) patients is it the maternal or paternal chromosome 15 that has the deletion?
The maternal chromosome (the parent isn’t always afflicted)
If a patient has PWS but does not have any deletion on the 15th chromosome what could the cause be?
2 Maternal copies (uniparental disomy). The disease is actually due to the lack of Paternal gene contribution.
If a patient has AS but does not have any deletion on the 15th chromosome what could the cause be?
2 Paternal copies (uniparental disomy). The disease is actually due to the lack of Maternal gene contribution.
What is the problem associated with uniparental disomy? Why do PWS and AS arise with uniparental disomy?
Imprinting (answers both questions). The differential modification of the maternal and paternal genetic contributions to the zygote resulting in the differential expression of parental alleles during development and in the adult. This happens at the epigenetic level.
Are all genes and chromosomes affected by imprinting?
No. For some genes or chromosomal regions it may be important to have maternal and paternal contribution, however, not all genes or all chromosomes.
How does imprinting occur?
Usually through methylation at the epigenetic level.
What is methylation? When does it occur? How long does it last?
Methylation is the addition of a methyl group to a cytosine residue in the DNA. The pattern of methylation can be different between males and females and lasts 1 generation. Change in methylation occurs at meiosis.
What happens to all male chromosomes during meiosis?
They are all reimprinted in the male version. The same is true for females.
What would happen during imprinting failure?
It is possible to have a child with one chromosme from dad and one from mom but both chromosomes have a male or female imprint.
How could you explain a PWS (or AS) patient that had NO uniparental disomy and NO deletion?
There was an imprinting error such that a grandmaternal chromosome 15 had gone through paternal meiosis WITHOUT being reimprinted. Thus, the father had transmitted a maternally imprinted chromosome to the child.
What are the 3 mutations that can give PWS?
1-Deletion of the paternal chromosome 15 resulting in only maternal alleles in that region.
2-Maternal uniparental disomy with only maternally imprinted alleles
3-An imprinting error, where the complement is comprised of one chromosome from dad and one from mom, but the paternal chromosome has maternal imprinting resulting in only maternal functional alleles.
What are the 3 mutations that can give AS?
1-Deletion of the maternal chromosome 15 resulting in only paternal alleles in that region.
2-Paternal uniparental disomy with only Paternally imprinted alleles
3-An imprinting error, where the complement is comprised of one chromosome from dad and one from mom, but the maternal chromosome has paternal imprinting resulting in only paternal functional alleles.
