Genomic Imprinting Flashcards
Biallelic Expression
Copies from each parent function equally in child
Changes from infancy to childhood in Prader-Willi Syndrome
Infancy: hypotonia and feeding difficulties; Childhood: uncontrolled appetite and obesity
Symptoms of Angelman Syndrome
Spasticity, seizures, seve MR, growth retardation
PW and Angelman deletion is often on…
del(15)(q11q13)
Epigenetic DNA modifications that influence gene expression are _____ but ______
heritable, reversible
Type of epigenetic mechanism in which parent-of-origin effects are transmitted through gametes
imprinting
Type of epigenetic mechanism that is heritable from cell to cell but not between generations
X inactivation
Dynamic epigenetic mechanism
DNA methylation
Maternal or paternal copy expressed? IGF2
paternal
Maternal or paternal copy expressed? KVLQT
maternal (but expression is biallelic in the heart)
Usually, imprinting is (on/off)
Off
Maternal or paternal copy expressed? SNRPN
Paternal
Maternal or paternal copy expressed in the brain? UBE3A
Maternal (but biallelic everywhere else)
Imprinting control region; sets the imprint for multiple genes during gametogenesis
Bipartite ICR
Why are maternal and paternal imprinting different?
One portion of ICR may be more active in males during gametogenesis, while one more active in females
3 Steps in the Imprinting Cycle
1) Imprinting “switched” during gametogenesis (to the correct gender-specific methylations)
2) Pattern maintained during development and in the somatic tissues
3) In the gametes, imprinting is wiped clean then re-imprinted (in a way that reflects the parent’s gender) to pass onto the next generation
How does parent-of-origin effect play a role in disease?
When there is only one allele that is typically active, disease occurs if that allele is disabled
What disease results from a paternal deletion: del(15)(q11q13)?
PWS
What disease results from a maternal deletion: del(15)(q11q13)?
AS
What is the result of an unequal crossover between low copy repeats?
microdeletions
How do hotspots relate to PWS?
The genes responsible for PWS (if deleted/disabled) are contained within regions where unequal crossover + microdeletions are frequent
Causes of PWS (3):
Paternal deletion; maternal uniparental disomy (with no paternal copies); mutation in imprinting center
Gene involved in PWS:
SNRPN
Gene involved in AS:
UBE3A
Causes of AS (4):
Maternal deletion; paternal uniparental disomy (no maternal); Mutation in imprinting center; UBE3A mutation
Uniparental Disomy
Individual inherits both chromosomes of one homologous pair from a single parent (and none from the other parent)
Cause of uniparental disomy:
2 separate nondisjunction events in gametogenesis/embryogenesis of individual
Trisomy rescue
Trisomy Rescue
Trisomy cause by maternal meiotic nondisjunction is “fixed” by chromosome LOSS through mitotic nondisjunction
Why does trisomy rescue occur?
There is a selective advantage
