genetic imprinting

Question 1

Epigenetic:

Answer 1

mitotically and meiotically heritable variations in gene expression that are not caused by changes in DNA sequence

Question 2

examples of epigenetics

Answer 2

Reversible, post-translational modifications of histones and DNA methylation are examples of epigenetic mechanisms that alter chromatin structure, thereby affecting gene expression.

Question 3

genetic imprinting is

Answer 3

epigenetic mechanism that regulates gene expression

Question 4

DNA methylation mediates

Answer 4

gene silencing

BUT CAN ALSO ACT AS AN ACTIVATOR

Question 5

DNA methylation is the epigenetic mark that mediates genetic imprinting

Answer 5

1. DNA methylation marks are established in gamete
2. DNA methylation is stably maintained in somatic cells
3. DNA methylation is reversible so that it can be reset during gametogenesis to transmit the appropriate sex specific imprint to progeny

Question 6

Prader willi symptoms

Answer 6

excessive eating
short stature
hypogonadism
some degree of intellectual disability

Question 7

angelman syndrome

Answer 7

short stature
sever intellectual disability
spasticity
seizures

Question 8

Angelman syndrome is caused by

Answer 8

defects in the expression of UBE3A, which encodes a ubiquitin ligase involved in early brain development.

Question 9

Prader-Willi syndrome is currently thought to arise due to

Answer 9

defects in SNORD116 snoRNA genes (non-coding RNAs typically involved in guiding modifications of other RNAs). In PWS, these small nucleolar RNAs may be involved in mRNA modification, possibly by modulating alternative splicing.

Question 10

imprinting

Answer 10

approximately 100 autosomal genes in the mammalian genome are inherited in a silenced state from one of the two parents, and in a transcriptionally active state from the other, thereby rendering the individual functionally hemizygous for these genes. This process has been referred to as parental imprinting, genetic imprinting, or gametic imprinting, and represents an important epigenetic mechanism of inheritance.

Question 11

recent investigations have revealed that in rare cases, _______ is present in the expressed allele of imprinted genes, and is excluded from the silenced allele.

Answer 11

DNA methylation

Question 12

DNA methylation as a gene silencing mechanism:

Answer 12

Hypermethylation may directly inhibit transcription either by repelling transcription factors (some DNA binding factors are known to be methylation-sensitive), or methylation may actively recruit factors that repress transcription.

Question 13

DNA methylation as a gene activation mechanism:

Answer 13

The molecular basis of this activation is poorly understood, but a current model postulates that DNA methylation may prevent the binding of a transcriptional repressor

Question 14

Characteristics of imprinted genes.

Answer 14

1. These genes tend to be clustered together rather than spread throughout the entire genome.
2. These clusters contain both maternally and paternally imprinted genes.
3. The imprinted genes encode both proteins and non-coding RNAs.

Question 15

To accomplish such epigenetic inheritance, _____

Answer 15

parental patterns of methylation, imprints, are erased in primordial germ cells as part of overall genomic reprogramming. New, sex-dependent imprints (patterns of methylation) are initiated during gametogenesis.

Question 16

DNA demethylation reactivates _______ and erases ______.

Answer 16

gene expression

parental methylation patterns in developing gametes

Question 17

demethylation could result from _____

Answer 17

inhibition of the maintenance methyltransferase, DNMT1, or indirectly, through the inactivation of chromatin-remodeling proteins.

Question 18

Erasure and resetting of the imprint appears to occur at _________, which contain non-coding DNA sequences that bind imprinter RNA transcripts (called _______) and recruit ________ complexes that methylate CpG islands located near the IC on the same chromosome (cis).

Answer 18

imprinting centers (IC)

BD transcripts

DNA methyltransferase (DNMT)

Question 19

DNMT complexes

Answer 19

methylate CpG islands located near the IC on the same chromosome (cis)

Question 20

Mutations at imprinting centers are

Answer 20

heritable lesions that can generate the same abnormal phenotypes brought about by deletions or uniparental disomies (see below) involving imprinted loci.

Question 21

Once sex-specific patterns of methylation are established during gametogenesis, the patterns are retained in somatic cells by

Answer 21

maintenance methylation, which is responsible for methylating the newly synthesized daughter strand of DNA after replication.

Question 22

Prader will is caused by

Answer 22

In 70% of patients, the syndrome is the result of a cytogenetically observable deletion involving the long arm of chromosome 15 (15q11-q13), occurring on the chromosome 15 homolog inherited from the patient’s father. These patients have a normal, maternally derived homolog of chromosome 15. However, this region on the maternally derived chromosome is methylated, and transcriptionally silenced.

Question 23

Angelman is caused by

Answer 23

These patients have a deletion of approximately the same region of chromosome 15 described above, but on the maternally derived homolog. In this case, the information contained on the normal paternally derived chromosome 15 is inactivated due to DNA methylation.

Question 24

uniparental disomy.

Answer 24

most commonly occurs when a trisomic conceptus (e.g. trisomy 15, maternal nondisjunction leading to two maternal, one paternal 15s) loses one of its extra chromosomes due to mitotic nondisjunction in early gestation.