Lecture 38: Genomic imprinting and epigenetics Flashcards
What is the term used for reproduction using just male genetic material?
androgenesis
Why can’t we reproduce asexually?
Two parents are required for mammalian development
What is androgenesis?
Androgenesis is a method for producing fish in which all the nuclear genetic information originates from the male parent (i.e., from the sperm) while the mitochondrial DNA is still maternally derived.
What is the term used for reproduction using just female genetic material?
parthenogenesis
What is pathenogenesis?
reproduction from an ovum without fertilization, especially as a normal process in some invertebrates and lower plants
What does androgenetic conception form in humans?
hydatidiform mole
What does parthenogenetic conception form in humans?
ovarian teratoma
What is a hydatidiform mole?
a cluster of fluid-filled sacs formed in the uterus by the degeneration of chorionic tissue around an aborting embryo / Benign tumour of trophoblastic tissue which develops at the placenta which may become malignant
What 3 tissues are not seen in ovarian teratomas?
1) skeletal muscle
2) membranes
3) placenta
What do androgenetic embryos usually result in? (3)
- Complete hydatidiform moles
- Proliferation of abnormal trophoblast tissue
- Can develop into malignant trophoblastic tumour
What is the usually genetic identification of androgenetic cells?
Mostly homozygous 46,XX
What are ovarian teratomas?
a bizarre tumor, usually benign, in the ovary that typically contains a diversity of tissues including hair, teeth, bone, thyroid, etc
A dermoid cyst develops from a totipotential germ cell (a primary oocyte) that is retained within the egg sac (ovary).
How are ovarian teratomas formed: Pathenogenetic or androgenetic?
Parthenogenetic conceptions
What is genomic imprinting?
an epigenetic phenomenon that causes genes to be expressed or not depending on whether they are maternal or paternal
How do ovarian teratomas form?
Derived from oocytes which have completed first or both meiotic divisions
Name 5 characteristics of ovarian teratomas?
- Diploid
- Wide spectrum of tissues
- Predominantly epithelial
- No skeletal muscle
- No membranes/placenta
Why do pathenogenetic embryos die?
embryos die due to failure of development of extraembryonic structures
(Trophoblast
Yolk sac)
Why do androgenetic embryos die at 6 somite stage?
Well developed extra-embryonic membranes
Poor embryo development
Why do uni parental conceptions fail?
Different roles of maternal vs. paternal genes in determining developmental fate
What are karyotypes and gene dosage like in uni parental conceptions?
Normal
What is genomic imprinting?
A mechanism that ensures the functional non-equivalence of the maternal and paternal genomes
Mothers and fathers somehow “imprint” their genes with a memory of their paternal or maternal origin
Is genomic imprinting encoded in the DNA nucleotide sequence?
No
When does genomic imprinting occur?
gametogenesis
True or false: genomic imprinting affects a very small subset of 100-200 genes
true
What in the genome does genomic imprinting affect?
Affects the expression of a small subset of 100-200 genes
Evolutionarily conserved
Depends on modifications to the genome laid down during gametogenesis
What is Angelman Syndrome?
a congenital condition characterized especially by intellectual disability and uncoordinated movement, typically resulting from loss of function of a gene present on the copy of chromosome 15 inherited from the mother
What are 4 symptoms of Angelman Syndrome?
- Facial dysmorphism (Prognathism, wide mouth, drooling Smiling/laughing appearance)
- Mental Handicap (Microcephaly
Absent speech) - Seizure disorder
- Ataxic, jerky movements
What is Prader- Willi syndrome?
a rare congenital condition characterized by excessive appetite, often leading to morbid obesity, and a variety of other signs including intellectual disability, short stature, and underdevelopment of the sexual organs, caused especially by the absence of certain genes normally present on the copy of chromosome 15 inherited from the father.
Name 5 characteristics of Prader-Willi syndrome?
- Infantile hypotonia
(Feeding problems
Gross motor delay) - Mental handicap
- Male hypogenitalism /cryptorchidism
- Small hands and feet
- Hyperphagia (Obesity)
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
Name a cytogenetic abnormality in AS/PWS?
Deletion of chromosome 15
Found in both Angelman and Prader-Willi syndromes
Always de novo
Recurrence risks very low
What is the Molecular mechanisms in Prader-Willi syndrome?
Uniparental disomy (25%) vs. del (70%)
Indistinguishable clinically
Lack of a paternal 15q11-13 contribution
What are the Molecular mechanisms in Angelman syndrome?
Deletion (75%)
UPD (1%)
Point Mutation (2-5%)
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 occur?
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)
