WEEK 13: 13.3 X-Chromosome Inactivation

Question 1

Why do males and females have distinct karyotypes?

Answer 1

as they have different sex chromosome complements

Question 2

What are the 2 types of sex chromosomes a human can have?

Answer 2

XY (male)
or
XX (female)

Question 3

Briefly explain the genetic evolution behind the formation of the Y chromosome (which is much smaller than the X chromosome)

Answer 3

it was a result of a testis-determining locus, sexually antagonistic alleles evolved at nearby loci; these differences were acted upon by natural selection & evolution (chromosome inversion, recombination & deletions), leading to a gene-poor Y chromosome

Question 4

What is PAR

Answer 4

pseudo autosomal regions (PAR) - the proximal and distal ends of each chromosomal pair have PAR which is similar between chromosomes

Question 5

Explain how balancing gene dosage is important?

Answer 5

• sex chromosome expression needs to be balanced with autosomes
• sex chromosome content needs to be balanced between males & females
  ,

Question 6

Males have a single x chromosome, compared to 2 of each autosome in females - what is the strategy to overcome this? and effect can this have?

Answer 6

the upregulation of the X chromosome in males, to balance x gene dosage.
Can lead to upregulated chromosome being passed onto an XX female, leads to disparity between males and females

Question 7

What have females developed as a result of upregulated chromosomes being passed onto an XX female?

Answer 7

an evolutionary mechanism known as X chromosome inactivation (XCI)

Question 8

Explain when/how XCI occurs, and what it results in

Answer 8

it occurs early in embryonic life
either the maternal/paternal X chromosome is switched off
it is a random process
will result in 50:50 mix of paternal & maternal chromosomes

Question 9

What is the inactivated chromosome referred to?

Answer 9

the ‘barr body’

Question 10

What is an Xist

Answer 10

a non-coding RNA, it does not code for a protein, its function is inactivated at the X chromosome inactivation centre

Question 11

explain the steps of initiation, spreading and maintenance?

Answer 11

1. Initiation: Xist RNA expressed from the X chromosome to be silenced (Xi)
2. Spreading: Xist RNA coats the entire Xi chromosome; recruits factors to induce heterochromatinization
3. Maintenance: heterochromatin structure and most genes on Xi are maintained and transmitted through somatic cell division