Genomic Imprinting and Epigenetics

What is the term used for reproduction using just male genetic material?

androgenesis

What is the term used for reproduction using just female genetic material?

parthenogenesis

What does androgenetic conception form in humans?

hydatidiform mole

What is a hydatidiform mole?

Benign tumour of trophoblastic tissue which develops at the placenta which may become malignant

What does parthenogenetic conception form in humans?

ovarian teratoma

What 3 tissues are not seen in ovarian teratomas?

1) skeletal muscle

2) membranes

3) placenta

What is genomic imprinting?

an epigenetic phenomenon that causes genes to be expressed or not depending on whether they are maternal or paternal

When does genomic imprinting occur?

gametogenesis

True or false: genomic imprinting affects a very small subset of 100-200 genes

true

What is the name of the imprinting abnormality characterised by a maternal deletion on chromosome 15:

Angelman Syndrome

Give 3 presentations associated with Angelman Sndyrome:

1) facial dysmorphism (wide mouth, smiling appearance)

2) mental handicap (microcephaly, absent speech)

3) ataxic, jerky movements

What is the name of the imprinting abnormality characterised by a paternal deletion on chromosome 15?

Prader-Willi syndrome

Give 4 presentations associated with Prader-Willi syndrome:

1) infantile hypotonia (gross motor delay, floppy limbs)

2) mental handicap

3) hyperphagia at around 4-5 causing obesity

4) male hypogenitalism

What genetic change causes both Angelman and Prader-Willi syndrome?

a deletion at chromosome 15

Is the deletion at chromosome 15 on the maternal or paternal chromosome in Angelman syndrome?

maternal

Is the deletion at chromosome 15 on the maternal or paternal chromosome in Prader-Willi syndrome?

paternal

What is the key mechanism of genetic imprinting?

DNA methylation

What enzyme is used to methylate DNA?

DNA methyltransferase enzymes

True or false: DNA methylation is irreversible

false

Where does DNA methylation ocur?

CpG islands (and CG nucleotides)

Does a methylated CpG island express or silence a gene?

silence

Give three ways in which chromatin can be molecularly modified:

1) phosphorylation

2) methylation

3) acetylation

What enzyme aids methylation of histones?

histone methyltransferase

What enzyme aids phosphorylation of histones?

protein kinases

What enzyme aids the removal of acetyl groups from histones?

histone deacetylase

Why do parental genes favour large babies?

it correlates with high foetal fitness

Why do maternal genes favour small babies?

it correlates with better maternal survival rate and reproductive fitness

What is Beckwith-Wiedemann syndrome?

large foetus syndrome (foetal overgrowth, organomegaly)

What is Russel-Silver syndrome?

small foetus syndrome (growth retardation, triangular face)

What gene is affected in both Beckwith-Wiedemann syndrome and Russel-Silver syndrome?

11p15.5

What causes Russel-Silver Syndrome?

hypomethylation causing both the maternal and paternal IGF2 genes to be silenced

What is the role of the IGF2 gene?

foetal growth promotion

What causes Beckwith-Wiedemann syndrome?

hypermethylation causing both maternal and paternal IGF2 to be expressed

True or false: imprinting is preserved in somatic development

true

What is imprint switching?

the swapping of imprinting patterns between paternal alleles to erase grandparental imprints and establish a new parental input

True or false: X inactivation is reversed in germ cells

true

True or false: it is random which X chromosome is inactivated

true

When does X inactivation occur?

early embryogenesis (when blastocyst has formed)

What is the name given to the split in cells with paternal vs maternal X inactivation?

mosaicism

What is the effect of mosaicism on female carriers of X-linked mutations?

carriers may present with a partial phenotype for the disease (skewing results in varied clinical expressions)