Genetic Imprinting Flashcards
What is epidemiology?
the study of mitotically and or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequences
how does epigenetics relate to imprinting?
gene silencing through methylation patterns on DNA
what is genetic imprinting?
autosomal genes are inherited in a silenced state from 1 parent and a activated state from the other parent
what is hemizygous?
only one gene is active or correctly expressed
when does imprinting take place?
during gametogenesis before fertilization
how is DNA methylation involved in gene silencing?
methylation of promoters can cause the gene to be silenced or by recruiting factors that repress transcription
how is DNA methylation involved in gene activation?
mechanism poorly understood, but current model states may prevent binding of transcriptional repressor
True or False
Imprinting must be reversible
True
must be wiped clean when gametogenesis occurs to pass da genes
what are the characteristics of imprinted genes?
- clustered together
- contain maternal and paternal imprinted genes
- encode both proteins and non-coding RNA’s
what are the essential characteristics of the epigenetic mark?
- modification must be established in gametes
2. allele modifications must be stably maintained after fertilization
what causes prader-willi and angelman syndrome?
deletion on long arm of chromosome 15
del 15 q11-q13
how does prader-willi syndrome come about?
deletion on the paternal chromosome with deactivated maternal chromosome
what is the presentation of patients with prader-willi syndrome?
- obesity
- excessive and indiscriminate eating
- short stature
- small hands and feet
- hypogonadism
- mental retardation
how does angelman syndrome come about?
deletion of maternal chromosome with deactivated paternal chromosome
what is the phenotype of angelman syndrome?
- unusual facial appearance
- short stature
- sever mental retardation
- spasticity
- seizures
what is the main way that you can discriminate phenotypically between angelman syndrome and prader-willi syndrome?
obesity is only present in prader-willi syndrome
what is uniparental disomy?
when child receives 2 paternal or maternal chromosome rather than 1 of each
what is the most common uniparental disomy?
trisomy 15 from maternal non-disjunction leading to 2 maternal and 1 paternal
if trisomy 15 is not compatible with life, how does a uniparetnal disomy occur?
non-disjunction early in gestation
how does demethylation of imprinted genes occur?
inhibition of maintenance methyltransferase (DNMT1, or through inactivation of chromatin-remodeling proteins
where does erasure and resetting of imprinting occur?
at imprinting centers
what does an imprinting center contain?
non-coding DNA sequences that bind imprinter RNA transcripts and recruit DNA methyltransferase (DNMT)
what is the function of DNA methyltransferases (DNMT)
complexes that methylate CpG islands located near IC on same chromosome
how is imprinting maintained after cell division of somatic cells?
maintenance methylation, have to methylate newly synthesized daughter strand
