X Inactivation In Females

[muffin10]

I've read that one of the X chromosomes in females is essentially inactivated (by methylation? I've dredged the term "Barr body" from my genetics of 40 odd years ago). However if one of the X chromosomes is inactivated, why do females not suffer from the same sex-linked defects that males do? Surely the cell can't be intelligent enough to "know" that the equivalent gene on the other X chromosome isn't working properly?

[Peter Pedant]

Oh the simple answer is - they are turned off at random
so half are one X and half are the other X in any organ .....

BUT... ( actually you could ask why all girls dont suffer from Turner Syndrome which is single X disease...)

Now if the liver came from one cell - then sort of half the women would suffer from X linked liver disease
but if it came from four cells - when deactivation occurred
then the one who had turned off all active X ( 1/16) would be severely affected with the X linked disease - and at the other end some lucky woman would have turned off all the damaged X cells
and the 14 in between would have a variation - almost normally distributed .....

This has been done for G6PD deficiency
and they found about 1 in 125 women had severe-ish deflciency
so you can conclude that the erythron ( whole of the red blood cell system) is derived from 7 totipotent cells - because 1/2 raised to power 7 is 1 in 128.

cool huh ?

( raised in a lecture in Cambridge in 1970 and then reviewed not by me in the NEJM in 1995 when everyone looked at me like I was fracking crazy. well you did ask: and have you seen the other absolute crip on the other threads today ?)

[muffin10]

Thanks Peter Pedant - I missed that it wouldn't be the same X in all cells. At what stage does the inactivation occur?

[Peter Pedant]

oops that wasnt covered
so I will let someone else answer that one

[Peter Pedant]

o jesus lardy daah ! Nature goes on and on about it - - here

https://www.nature.com/scitable/topicpage/X-Chromosome-X-Inactivation-323

[muffin10]

Thanks again, Peter Pedant. The later, random, inactivation explains all.

Interesting example of both a "sense" and an "antisense" transcription of DNA to RNA having a function.

[Peter Pedant]

amazing what they have found - altho quite a lot of 'must be'

we were told once a gene was hypermethylated that was it

yeah XIST and TSIX and thought blimey !

anyway thx I wouldnt have found the nature review w/o yr q

[Peter Pedant]

// Surely the cell can't be intelligent enough to "know" that the equivalent gene on the other X chromosome isn't working properly?//

bit prophetic there

now they are saying one X 'knows' the other one is switched off....