Epigenetics

In Apis mellifera bees, what determines if a bee becomes a worker bee or a queen

Their diet

What is a mosaic

A mosaic is an individual who arose from a single fertilized egg, but who has 2 or more populations of cells each with different genotypes

Are both X chromosomes in females active

No

What makes this cat 2 different colours

Random exon activation

Random X-chromosome inactivation explains tortoiseshell or calico (3+ colors) in females

Turner Syndrome traits/symptoms

• Coarctation of aorta or bicuspid aortic valve

• Webbed neck and lymphedema (sometimes)

• Kidney problems – horseshoe kidney

• Amenorrhea

• Non-functional ovaries (streak gonads) – infertile

• Non verbal learning disabilities and behavioural problems - variable

Turner Syndrome cause

Turner syndrome occurs due to anaphase lag – where one sex chromosome moves too slowly to the pole of the daughter cell during division

It can happen:

• During gametogenesis - classical monosomy X – 45,X

• During early mitotic division - Turner Mosaicism – 45X/46XX or 45X/46XY

Is turner syndrome / Turner Mosaicism inherited

No - neither

Treatment options & priorities for Turner Syndrome

What would be 4 key tests/investigations to assess people diagnosed with Turner syndrome

Karyotype – translocation?

Cardiac function tests

Cardiac imaging - CT, MRI, MRA

Y chromosome PCR

Why would 45,X be a problem for women but men can live with just 1 X chromosome

There are genes that are on both the X and Y chromosomes that need to be expressed twice to function.

The inactivation of the 2nd X chromosome is incomplete - it still has a few active gene. (Up to 25% of X chromosome genes partially or totally escape (including PAR genes e.g. SHOX))

Escape genes expressed in higher/lower levels in normal women versus Turner women

Higher

Function of genes outside PARs

Genes outside PARs may contribute to female phenotype

Tetragametic Chimerism

2 Oocytes + 2 Sperm

2 Zygotes that Merge into one Organism

Chimaerism vs Mosaicism

Chimaera = an individual with 2 or more populations of cells with different genotypes who arose by fusion of more than one fertilised zygote during embryogenesis

Mosaic = an individual with 2 or more populations of cells with different genotypes who arose from a single fertilised egg

Mosaic usually results from what

somatic change during early replication

What can Germline mosaicism result in

Germline mosaicism occur early in germ cell development, resulting in a significant no. of gametes that carry the mutation and thus can affect >1 child

Robert has an allele of Insulin Like Growth Factor 2 (IGF2) from Don – which works

He has an allele of Insulin Like Growth Factor 2 from Betty that is switched off (imprinted)

If Robert Draper has a child, which allele of the IGF2 gene will work?

If Robert (the father) has a child, whichever version of the allele (from Don or from Betty) that is present in his sperm will be switched on

Explain the mechanism behind this

Role of IGF2 in gestation

Regulate growth

Give an example of what can occur as a result of loss of imprinting (LOI) of maternal IGF2

Wilms’ tumour is an embryonic kidney cancer associated with loss of imprinting (LOI) of maternal IGF2

If both IGF2 alleles should begin to be expressed in a cell, what can be the result

That cell may develop into cancer

What deletion is associated with Prader Willi

Deletion from paternal Chr 15 (15q11-q13)

What deletion is associated with Angelman syndrome

Deletion from maternal Chr 15 (15q11-q13)

What would a child with paternal uniparental disomy for Ch 15 have ?

Child is missing a maternal Ch15 – therefore Angelman’s syndrome (vice versa for Prader Willi)

Is it possible for an individual with Prada Willi syndrome to have BOTH maternal and paternal chromosomes

Yes - the paternal chromosome may have maternal pattern of methylation (effectively no paternal chromosome) due to:

• Epigenetic (imprinting) error

• Mutations in the imprinting control centre

Is it possible for an individual with Angelman syndrome to have BOTH maternal and paternal chromosomes

The maternal chromosome may have the paternal pattern or methylation due to:

• Epigenetic (imprinting) error

• Mutations in the imprinting control centre

X-inactivation is incomplete - up to 25% of X chromosome genes partially or totally escape (including PAR genes), which has implications for what

gene dosing

Diseases related to imprinting can occur due to  what 4 causes

Diseases related to imprinting can occur due to UPD or a mutation in the imprinting control centre, as well as deletion/mutation of the genes themselves on the relevant Chr