Genetic Imprinting

Question 1

What is epigenetics?

Answer 1

Heritable changes in gene expression that occur without a change in DNA sequence

i.e. reversible post-translational modification of histones and pattern of DNA methylation

Question 2

How do modifications of DNA and chromatin affect gene expression?

Answer 2

DNA demethylation reactivates gene expression (erases parental methylation patterns in developing gametes)

Question 3

What is the molecular basis for genetic imprinting?

Answer 3

Allele-specific methylation of CpG dinucleotides of imprinted genes

Question 4

What are the different fates of DNA methylation imprinting patterns in germ line and somatic cells?

Answer 4

Methylation can lead to gene silencing or expression

Silencing via hypermethylation that directly inhibits transcription or methylation to recruit repressors

Expression via (maybe) methylation to prevent repressors from binding

Question 5

What is the relevance of genetic imprinting in Prader-Wili and Angelman syndromes?

Answer 5

With Prader-Willi syndrome there is a cytogenetically observable deletion on the long arm of C15 from the paternally inherited homolog, whereas the maternal derived homolog is normal yet methylated and thus transcriptionally silenced.

Angelman syndrome is the same as for Prader-Willi except that the role of the maternal and paternal homologs are reversed.

Question 6

What is the origin of uniparental disomy?

Answer 6

Uniparental disomy occurs when a trisomic conceptus loses one of its extra chromosomes (due to mitotic nondisjunction in early gestation)
=> it may result in an abnormal phenotype when both remaining homologs are from the same parent

Question 7

What are three characteristics of imprinted genes?

Answer 7

1. Tendency to be clustered rather than spread throughout genome
2. Clusters contain maternal and paternal imprinted genes
3. Imprinted genes encode both proteins and non-coding RNAs

Question 8

What are the essential characteristics of the epigenetic mark?

Answer 8

1. Modification must be established in the gametes
2. The allelic modification must be stably maintained after fertilization
3. The modification must be capable of being erased and reset during production of germ cells