14 Genome imprinting

Question 1

What is a hydatiform mole?
How does it occur?
Risk?

Answer 1

Proliferation of trophoblast tissue, no embryo.
Androgenesis (male only development). Homozygous 46XX.
May develop into malignant trophoblastic tumour.

Question 2

What is the result of parthenogenesis?

Tissue?

Answer 2

Benign ovarian teratomas. Diploid.

Wide tissue spectrum with mostly epithelial tissue.

Question 3

Why do parthenogenic pregnancies fail?

Answer 3

Failure of trophoblast and yolk sac development.

Question 4

When do androgenetic embryos die?

Why?

Answer 4

6 somite stage.

Poor embryo development.

Question 5

What is genomic imprinting?
Why?
When does it occur?

Answer 5

Epigenetic changes affecting 100-200 genes.
Ensures functional non-equivalence of maternal and paternal genes.
Laid down during gametogenesis.

Question 6

What are the clinical features of Angelman syndrome? (7)

Answer 6

‘Puppet child’.

Prognathism, wide mouth, smiling appearance, microcephaly, absent speech, seizures, jerky movements.

Question 7

What are the clinical features of Prader-Willi syndrome? (5)

Answer 7

Infant hypotonia. Mental handicap. Male hypogonadism. Small hands and feet. Hyperphagia -> obesity.

Question 8

What is the cytogenetic abnormality in Angelan syndrome and Prader-Willi syndrome?

Answer 8

De novo deletion of chromosome 15.

Question 9

What is the molecular mechanism of Prader-Willi syndrome?

Cause? (2)

Answer 9

Lack of a paternal 15q11-13 contribution.

Deletion (70%) or uniparental disomy.

Question 10

What is the molecular mechanism of Angelman syndrome?

Cause (3)

Answer 10

Lack of maternal UBE3A contribution.

Deletion (75%), uniparental disomy (5%), point mutation (1%).

Question 11

What is DNA methylation?

Answer 11

Reversible epigenetic change occurring at CG dinucleotides.

Question 12

How does DNA methylation work?

Answer 12

Shuts down transcription to ensure mono allelic expression.

Question 13

Which enzymes are involved in epigenetic changes? (5).

Answer 13

DNA methyltransferase.
Histone methyltransferase.
Histone deacetylase.
Ubiquitin protein ligase.
Protein kinases.

Question 14

What is the foetal-maternal growth conflict?

Answer 14

Larger babies -> increased maternal death.
Therefore maternal genes favour smaller babies.
Polygamous father favours larger baby.

Question 15

What is Beckwith-Wiedermann syndrome?

Features? (4)

Answer 15

Foetal overgrowth ± normal adult size.
Organomegaly.
Hypoglycaemia.
Asymmetry and tumour risk.

Question 16

What is Russell-Silver syndrome?

Features? (3)

Answer 16

Growth retardation extending post-natally.
Triangular face (brain development preserved).
Asymmetry.

Question 17

What is the genetic basis of Beckwith-Wiedermann syndrome and Russel-Silver syndrome?

Answer 17

11p15.5: Insulin-like growth factor 1. (Foetal growth promotor).
BW: hypermethylation.
RS: hypomethylation.

Question 18

What is imprint switching?

Answer 18

Parental imprint remembered in somatic development.

Forgotten before gametogenesis to establish new parental imprint.

Question 19

What are pseudoautosomal regions?

Answer 19

Small regions on X and Y chromosomes with the same genes.

Question 20

When does X-inactivation occur?

Answer 20

Blastocyst stage.

Question 21

How is imprinting different to X-inactivation?

Answer 21

Whole chromosome is silenced in X-inactivation.

Question 22

Name three diseases affected by random skewing of X-inactivation:

Answer 22

Duchenne muscular dystrophy.
Haemophilia.
Hypohidrotic ectodermal dysplasia.

Question 23

What does hypohidrotic ectodermal dysplasia result in?

Test?

Answer 23

Patches of skin without sweat glands.

Starch/iodine test.