Genetic Imprinting Flashcards
Prader-Willi syndrome is characterized by _____.
obesity, excessive and indiscriminate eating, short stature, small hands and feet, hypogonadism, and intellectual disabilities
imprinting
genes that are functionally hemizygous because one parental allele is silenced; a sex-dependent epigenetic modulation
The imprinted genes encode both ________ and ________.
proteins and non-coding RNAs
The inherited form of _________ is exclusively inherited from mothers
Angelman syndrome
DNA methylation is maintained in __________.
somatic cells after fertilization
uniparental disomy
inheriting two copies of a chromosome from one parent, or no copies from one parent
Uniparental disomy most commonly occurs when a trisomic conceptus loses one of its extra chromosomes due to _______.
mitotic nondisjunction in early gestation
What is one sex-dependent epigenetic modulation mechanism?
imprinting
Angleman Syndrome patients have a deletion of approximately the same region of chromosome 15 as Prader-Willi patients but on the _____ derived homolog.
maternally
_________ is characterized by obesity, excessive and indiscriminate eating, short stature, small hands and feet, hypogonadism, and intellectual disabilities.
Prader-Willi syndrome
The 15q11-q13 region contains ____ paternally expressed genes.
three
Uniparental disomy most commonly occurs when a trisomic conceptus loses _______ due to mitotic nondisjunction in early gestation.
one of its extra chromosomes
Demethylation could result from the inhibition of _____, or indirectly through the inactivation of chromatin-remodeling proteins.
the maintenance methyltransferase, DNMT1
How many human genes are imprinted?
about 1%
How does CpG methylation affect gene expression?
chromatin structure is compacted to repress transcription
DNA methylation is established _________.
in the gamete
DNA methylation is the epigenetic mark that mediates __________.
genetic imprinting
Which chromosome is mutated to result in Prader-Willi and Angleman Syndrome?
15
To accomplish such epigenetic inheritance, parental patterns of methylation are erased in ______ as part of overall genomic reprogramming.
primordial germ cells
The chromosomal sorting error in uniparental disomy “rescues” the developing pregnancy from spontaneous abortion but may result in an abnormal phenotype if both remaining homologs are derived from _______.
the same parent
15q11-13 locus relevance
uniparental disomy - Prader-Willi and Angelman Syndrom
________ could result from the inhibition of the maintenance methyltransferase, DNMT1, or indirectly through the inactivation of chromatin-remodeling proteins.
Demethylation
epigenetic
mitotically and meiotically inheritable variation in gene expression that is not caused by a change in DNA sequence
In addition to parent of origin effects due to deletions, genetic imprinting also leads to abnormal phenotypes in association with ______.
uniparental disomy
Imprinted gene clusters contain both _____ and ______ imprinted genes.
maternally and paternally
In uniparental disomy, if both remaining 15 homologs are maternal in origin, both carry maternally repressed loci, but normal development is dependent on expression of genes at the missing _______.
paternal locus
Which trisomies can survive to live birth?
13, 18, and 21
DNA methylation is __________ so that it can be reset during gametogenesis.
reversible
Erasure and resetting of the imprint appears to occur at _______.
imprinting centers (IC)
What would happen if methylation marks are not erased during gametogenesis?
total silencing of both copies of the gene would occur at a very high rate
______ is characterized by an unusual facial appearance, short stature, severe intellectual disabilities, spasticity, and seizures.
Angelman syndrome
What enzyme methylates a histone?
histone methyltransferase
Where is the promoter region normally found?
near the centromere
New, sex-dependent imprints (patterns of methylation) are initiated during ___________.
gametogenesis
In 70% of Prader-Willi patients, the syndrome is the result of a cytogenetically observable _____ involving the long arm of chromosome 15 (15q11-q13), occurring on the chromosome 15 homolog inherited from the patient’s _____.
deletion; father
What recognizes hemi-methylated DNA strands and methylates the newly synthesized strand?
maintenance methyltransferase
What is the job of a maintenance methyltransferase?
recognize hemi-methylated DNA strands and methylate the newly synthesized strand
___________ is the epigenetic mark that mediates genetic imprinting.
DNA methylation
Which two syndromes are caused by maintenance of methylation marks during gametogenesis?
1) Prader-Willi 2) Angleman syndrome
Imprinting centers (IC) contain non-coding DNA sequences that bind imprinter _____ and recruit DNA methyltransferase (DNMT) complexes that methylate CpG islands located near the IC on the same chromosome (cis).
RNA transcripts (BD transcripts)
__________ is when genes are functionally hemizygous because one parental allele is silenced.
Imprinting
________ most commonly occurs when a trisomic conceptus loses one of its extra chromosomes due to mitotic nondisjunction in early gestation.
Uniparental disomy
Demethylation could result from the inhibition of the maintenance methyltransferase, DNMT1, or indirectly through the _______.
inactivation of chromatin-remodeling proteins
Two epigenetic mechanisms?
1) reversible, post-translational modifications of histones 2) DNA methylation
Mutations at ______ are heritable lesions that can generate the same abnormal phenotypes as deletions or uniparental disomies.
imprinting centers
What is the molecular basis for genetic imprinting?
Methylation of cytosine residues in CpG residues of promoter regions
Once sex-specific patterns of methylation are established during gametogenesis, the patterns are retained in somatic cells by _______.
maintenance methylation
15q11-q13 region genes encode proteins for ______.
placental development, fetal growth
