Sex Chromosomes

Question 1

What is dosage disequilibrium with regards to the X chromosome?

Answer 1

• Females have 2 copies of X vs 1 in males
• If both transcribed then females would have twice the dosage of gene products as men
• X inactivation combats this

Question 2

X and Y share a common sequence at the tip of the short arm - what is this called?

Answer 2

Pseudoautosomal region (PAR1). A second PAR exists at the tip of the long arm

Question 3

Provide info on the behaviour of X and Y at meiosis

Answer 3

• X and Y only able to synapse across PARs
• The rest remain unpaired (= XY bivalent)
• Regions of asynapsis not usually tolerated at meiosis so X and Y form sex vesicle

Question 4

Provide more info on the PAR1 region of X and Y

Answer 4

• Xpter/Ypter
• does not undergo X inactivation
• includes SHOX gene (candidate for short stature)

Question 5

What region of the X chromosome is associated with X inactivation centre?

Answer 5

Xq13 (XIST gene)

Question 6

Proximal Yq is a specific region associated with what condition?

Answer 6

Gonadoblastoma

Question 7

What part of the Y chromosome is a heterochromatin block (non coding)?

Answer 7

Distal Yq

Question 8

X inactivation is not complete. What escapes?

Answer 8

The Pseudoautosomal regions and a small number of genes scattered across the rest of the chromosome

Question 9

What is an alternative name for X inactivation?

Answer 9

Lyonisation

Question 10

The darker stained inactive X in the interphase nucleus is often referred to as what?

Answer 10

Barr body

Question 11

At what stage does X inactivation take place?

Answer 11

2 weeks post-fertilisation: 5,000 cell stage

Question 12

Give a good example from the animal kingdom of X inactivation

Answer 12

Patchy coat of tortoiseshell cats - one gene has two alleles and depending on which X is inactivated individual cells will express the appropriate colour from the active X

Question 13

What other epigenetic changes are involved in the maintenance of X inactivation?

Answer 13

Methylation and histone acetylation

Question 14

How can X inactivation impact on X:autosome rearrangements?

Answer 14

• If derivative X:autosome chromosome includes XIC then that chromosome can be inactivated, spreading from X segment into the autosome
• If it does not carry XIC then X chromosome material in that chromosome cannot be inactivated

Question 15

What are the viable consequences of X:autosome rearrangements?

Answer 15

In cells where normal X is inactivated the derivative segments of X remaining active equate to one whole X chromosome resulting in functional balance

Question 16

What are the non-viable consequences of X:autosome rearrangements?

Answer 16

• In cells where derivative X is inactivated the normal X and segment of X on derivative chromosome (minus XIC) remain active
• Gene overdose occurs for those in the derivative segment
• The segment of autosome on derivative X is also inactivated giving monosomy for that section

Question 17

How does non-random X inactivation occur in a balanced carrier?

Answer 17

• The non-viable cells fail to divide

- Majority of cells within the body derived from cells with inactivation of the normal X

Question 18

What are the consequences of non-random X inactivation?

Answer 18

May result in expression of sex-linked disorders in females

Question 19

How does non-random X inactivation differ in an unbalanced carrier?

Answer 19

Cells where abnormal X is inactivated are viable whereas those where the normal X is inactivated are non-viable