14 Genome imprinting Flashcards
What is a hydatiform mole?
How does it occur?
Risk?
Proliferation of trophoblast tissue, no embryo.
Androgenesis (male only development). Homozygous 46XX.
May develop into malignant trophoblastic tumour.
What is the result of parthenogenesis?
Tissue?
Benign ovarian teratomas. Diploid.
Wide tissue spectrum with mostly epithelial tissue.
Why do parthenogenic pregnancies fail?
Failure of trophoblast and yolk sac development.
When do androgenetic embryos die?
Why?
6 somite stage.
Poor embryo development.
What is genomic imprinting?
Why?
When does it occur?
Epigenetic changes affecting 100-200 genes.
Ensures functional non-equivalence of maternal and paternal genes.
Laid down during gametogenesis.
What are the clinical features of Angelman syndrome? (7)
‘Puppet child’.
Prognathism, wide mouth, smiling appearance, microcephaly, absent speech, seizures, jerky movements.
What are the clinical features of Prader-Willi syndrome? (5)
Infant hypotonia. Mental handicap. Male hypogonadism. Small hands and feet. Hyperphagia -> obesity.
What is the cytogenetic abnormality in Angelan syndrome and Prader-Willi syndrome?
De novo deletion of chromosome 15.
What is the molecular mechanism of Prader-Willi syndrome?
Cause? (2)
Lack of a paternal 15q11-13 contribution.
Deletion (70%) or uniparental disomy.
What is the molecular mechanism of Angelman syndrome?
Cause (3)
Lack of maternal UBE3A contribution.
Deletion (75%), uniparental disomy (5%), point mutation (1%).
What is DNA methylation?
Reversible epigenetic change occurring at CG dinucleotides.
How does DNA methylation work?
Shuts down transcription to ensure mono allelic expression.
Which enzymes are involved in epigenetic changes? (5).
DNA methyltransferase. Histone methyltransferase. Histone deacetylase. Ubiquitin protein ligase. Protein kinases.
What is the foetal-maternal growth conflict?
Larger babies -> increased maternal death.
Therefore maternal genes favour smaller babies.
Polygamous father favours larger baby.
What is Beckwith-Wiedermann syndrome?
Features? (4)
Foetal overgrowth ± normal adult size.
Organomegaly.
Hypoglycaemia.
Asymmetry and tumour risk.
What is Russell-Silver syndrome?
Features? (3)
Growth retardation extending post-natally. Triangular face (brain development preserved). Asymmetry.
What is the genetic basis of Beckwith-Wiedermann syndrome and Russel-Silver syndrome?
11p15.5: Insulin-like growth factor 1. (Foetal growth promotor).
BW: hypermethylation.
RS: hypomethylation.
What is imprint switching?
Parental imprint remembered in somatic development.
Forgotten before gametogenesis to establish new parental imprint.
What are pseudoautosomal regions?
Small regions on X and Y chromosomes with the same genes.
When does X-inactivation occur?
Blastocyst stage.
How is imprinting different to X-inactivation?
Whole chromosome is silenced in X-inactivation.
Name three diseases affected by random skewing of X-inactivation:
Duchenne muscular dystrophy.
Haemophilia.
Hypohidrotic ectodermal dysplasia.
What does hypohidrotic ectodermal dysplasia result in?
Test?
Patches of skin without sweat glands.
Starch/iodine test.
