Bioinformatics, gene to function to clinic, genomic imprinting

Question 1

What does LCA stand for?

Answer 1

Leber’s congenital amaurosis

Can only see very limited central vision

Question 2

Gene therapy treatments for LCA and why?

Answer 2

Eye is immune privileged and accessible for subretinal injection.
RPE65 gene in dogs.

Question 3

Pharmacogenetics definition

Answer 3

Correlation between the effect of drugs and the genetic constitution of patients

Question 4

Cytochrome P450 oxidases

Answer 4

Multigene family of enzymes found in liver. Responsible for metabolic elimination of most drugs in use.

Question 5

What CYP2D6?

Answer 5

highly polymorphic cytochrome 450 family member.
Metabolises 25% of drugs
People can be non-metabolisers or ultra-rapid metabolisers

Question 6

Parthenogenesis definition

Answer 6

Asexual reproduction in which the offspring develops from unfertilised eggs

Question 7

Androgenesis definition

Answer 7

Embryo fails to develop but the trophoblastic tissues develop normally

Question 8

Hydatidiform mole definition

Answer 8

Hydatidiform mole is a rare mass or growth that forms inside the womb (uterus) at the beginning of a pregnancy. It is a type of gestational trophoblastic disease

Question 9

Androgenetic hydatidiform mole

Answer 9

Complete moles which most are homozygous (46, XX)

Proliferation of abnormal trophoblast tissue

Question 10

Parthenogensis what is it?

Answer 10

Benign ovarian teratomas
Derived from oocytes which have completed first or both meiotic divisions.
They’re diploid and produce wide spectrum of tissues but mainly epithelia

Question 11

Uniparental conceptions in the mouse how successful are they?

Answer 11

Parthenogenetic embryos die due to failure of extraembryonic structures (trophoblast, yolk sac)

Androgenetic embryos die at 6 somite stage so has well developed extra-embryonic structures but poor embryo development

Question 12

Why do uniparental conceptions fail? They have normal karyotype and normalgene dosage.

Answer 12

Different roles of maternal vs paternal genes.
Concept of genomic imprinting: mothers and fathers somehow imprint their genes with a memory of their materal or paternal origin.

Question 13

Genomic imprinting definition

Answer 13

A mechanism that ensures the functional non-equivalence of the maternal and paternal genomes

Question 14

Features of genomic imprinting

Answer 14

Not encoded in the DNA nucleotide sequences i.e. epigenetic

Determined via modifications to the genome in gametagensis (spermatogenesis vs oogenesis)

Question 15

Angelman syndrome

Answer 15

Facial dysmorphism
Mental handicap
Seizure disorder
Ataxic, jerky movements
Aka puppy disorder

Question 16

Prader-Willi syndrome

Answer 16

Infantile hypotonia
Mental handicap
Male hypogenitalism/ cryptorchidism 
Small hands and feet
Hyperphagia - obesity
Stereotypic behaviour

Question 17

Cytogenetic abnormalities for Angelman and Prader-Willi syndrome

Answer 17

Deletion of chromosome 15
Found in both syndromes
Always de novo risks so recurrence risks very low
Syndrome dependent on if its on male or female side.

Dependent on methylation

Question 18

Features of DNA methylation

Answer 18

Post-synthetic DNA modification
Epigenetic so does not normally alter DNA sequence
DNA methyltransferases
Reversible
Has to be maintained following replication
Occurs at CG dinucleotides, many promoter regions are spared making CG islands

Question 19

What is Beckwith-Widemann Syndrome?

Answer 19

Foetal overgrowth - high birthweight (>5kg)
Organomegaly
Hypoglycaemia
Asymmetry
Tumour risk
Sporadic occurrence 
Epigenetic abnormalities

Question 20

Russell-Silver syndrome

Answer 20

Growth retardation
Triangular face (preserves more brain size)
Asymmetry
Sporadic occurrence

Question 21

Hypomethylation of 11p15.5 for IGF2 (insulin-like growth factor 2)

Answer 21

Less IGF2 production

Russell-Silver Syndrome

Question 22

Hypermethylation of 11p15.5 for IGF2

Answer 22

More IGF2 leads to Beckwith-Widemann syndrome

Question 23

Imprint switching features

Answer 23

Forgotten before gametogenesis

Establishes new parental imprint during gametogenesis

Question 24

Features of a female carrier of an XL mutation

Answer 24

Hypohidrotic ectodermal dysplasia
Starch/iodine test
Patches of skin with or without sweat glands

Question 25

When does X inactivation occur?

Answer 25

At a time when there are a small number of precursor cells.
Random skewing is possible
For carriers of XL mutations this affects clinical expression
It is unpredictable

Question 26

Consequences of X inactivation

Answer 26

Females are epigenetic mosaics
Composed of patches of cells working on or other X chromosome
Carriers of XL mutations have some functionally defective and some normal cells
The consequence of this functional mosaicism may be unpredictable and may also be disease specific