Does X-Inactivation always occur?

[Avery07]

I never remember going over X-Inactivation in my genetics class and just came across it DAT studying.

From my understanding, this phenomenon occurs in all females?? That's my take on it but none of the resources I'm working with come out and say that it always happens.

I want to doubt that it is always happening based on the fact that recessive traits should still be occurring at the same rate of males (for those residing on the X chromosome). I mean, the only reason that these rates are lower is that they have another X chromosome to protect them from the recessive trait however if this chromosome is inactivated then there should be no difference??

Shed some light please.


Edit:

If you can, try to explain my XXY argument in post 3

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[UCB05]

I never remember going over X-Inactivation in my genetics class and just came across it DAT studying.

From my understanding, this phenomenon occurs in all females?? That's my take on it but none of the resources I'm working with come out and say that it always happens.

I want to doubt that it is always happening based on the fact that recessive traits should still be occurring at the same rate of males (for those residing on the X chromosome). I mean, the only reason that these rates are lower is that they have another X chromosome to protect them from the recessive trait however if this chromosome is inactivated then there should be no difference??

Shed some light please.

yes, it always happens. Having both copies of an X chromosome transcribing would wreak havoc on female cells. One X chromosome is packaged and inactivated, leaving what is called a Barr Body. As far as I can tell, it's random which chromosome is inactivated in each cell, and for that reason females are technically chimeras (genetic mosaic) of two different X chromosomes being expressed.

As far as dominance/recession, keep in mind that even with a recessive gene being expressed in the intact cell of a heterozygote, statistically 50% of all other cells will have a perfectly fine chromosome whose expression masks the phenotype of the recessive gene elsewhere.
If it's a bad nonsense mutation, other cells usually compensate for it with a good copy of the protein. If the mutated protein is deleterious such that its presence cannot be compensated for by the wild type protein, that would imply dominance anyway.

Also keep in mind inactivation occurs early on so it's likely one local set will have the same X inactivated

 

[Avery07]

Furthermore--

I am just finding out that this X-Inactivation can occur in XXX females (in which two X chromosomes become inactivated) and in XXY males (in which one X chromosome becomes inactivated).

This brings me to a concern regarding XXY males and Klinefelter's Syndrome.

From what I remember regarding this genetic disorder, a male inherits an extra X chromosome-- I'm assuming this is from nondisjunction. Whatever the case may be, the bottom line was that due to this extra X chromosome, the male suffers from feminine-like characteristics to include breast development, less facial and chest hair, smaller testicles, female-like pubic hair pattern, wide hips, and in most cases infertility.

If one of these X chromosomes is inactivated then essentially wouldn't that just make the male function as a normal XY male? I mean the Y chromosome should provide the manliness and if anything, the extra X chromosome should provide greater genetic variation as some cells will be XaXiY and others will be XiXaY (where a is activated and i is inactivated). In my mind this genetic disorder should increase fitness instead of decreasing.

Ugh. I think this calls for a trip to my old genetics professor.

 

[Avery07]

yes, it always happens. Having both copies of an X chromosome transcribing would wreak havoc on female cells. One X chromosome is packaged and inactivated, leaving what is called a Barr Body. As far as I can tell, it's random which chromosome is inactivated in each cell, and for that reason females are technically chimeras (genetic mosaic) of two different X chromosomes being expressed.

As far as dominance/recession, keep in mind that even with a recessive gene being expressed in the intact cell of a heterozygote, statistically 50% of all other cells will have a perfectly fine chromosome whose expression masks the phenotype of the recessive gene elsewhere.
If it's a bad nonsense mutation, other cells usually compensate for it with a good copy of the protein. If the mutated protein is deleterious such that its presence cannot be compensated for by the wild type protein, that would imply dominance anyway.

Also keep in mind inactivation occurs early on so it's likely one local set will have the same X inactivated

Try to explain the XXY phenomenon then.

And what do you mean by local set? I've found that X-inactivation occurs around the 12-16 day in embryonic development for humans. At that time, the X-inactivation is random with regards to which X chromosome becomes inactivated however at that point in time, each daughter cell retains the same inactivated chromosome.

This would result to a large variability in which X is inactivated in any given cell.

Are you saying that a local set should be dependent upon the same embryonic parent cell (ie- a certain set of nerve cells all date back to one embryonic cell?) This makes sense. However if that is the case, it debunks your hypothesis on creating enough "good" protein to overcome a recessive deficiency as all cells (from a localized line) should be creating the same protein.

Do you know how colorblindness works? I'm trying to fit this X-inactivation in that context. If it is just a result of making a good protein as opposed to making a bad recessive protein then this answers my question as to why don't females suffer the same X-Linked recessive disorders however I'm thinking color blindness is the result of something else.

 

[UCB05]

Furthermore--

I am just finding out that this X-Inactivation can occur in XXX females (in which two X chromosomes become inactivated) and in XXY males (in which one X chromosome becomes inactivated).

This brings me to a concern regarding XXY males and Klinefelter's Syndrome.

From what I remember regarding this genetic disorder, a male inherits an extra X chromosome-- I'm assuming this is from nondisjunction. Whatever the case may be, the bottom line was that due to this extra X chromosome, the male suffers from feminine-like characteristics to include breast development, less facial and chest hair, smaller testicles, female-like pubic hair pattern, wide hips, and in most cases infertility.

If one of these X chromosomes is inactivated then essentially wouldn't that just make the male function as a normal XY male? I mean the Y chromosome should provide the manliness and if anything, the extra X chromosome should provide greater genetic variation as some cells will be XaXiY and others will be XiXaY (where a is activated and i is inactivated). In my mind this genetic disorder should increase fitness instead of decreasing.

Ugh. I think this calls for a trip to my old genetics professor.

There are also a couple of genes that are not inactivated on X and Y chromosomes, expressed in the same way as autosomal genes with two copies. Extra copies of X chromosomes can mess up this balance, and I would assume this is what leads to some abnormalities in those nondisjunction diseases you mentioned. IMO in the grand scheme of human form and function, the fact that XXX and XXY individuals are almost normal despite having an extra sex chromosome is a testament to the efficacy of X-inactivation.

 

[Avery07]

There are also a couple of genes that are not inactivated on X and Y chromosomes, expressed in the same way as autosomal genes with two copies. Extra copies of X chromosomes can mess up this balance, and I would assume this is what leads to some abnormalities in those nondisjunction diseases you mentioned. IMO in the grand scheme of human form and function, the fact that XXX and XXY individuals are almost normal despite having an extra sex chromosome is a testament to the efficacy of X-inactivation.

OK-- I did come across something saying that the entire chromosome is not inactivated and that small segments can remain active which would explain XXY as you explained.

Thanks for the help. Do you know anything on the mechanism of colorblindness?

 

[UCB05]

OK-- I did come across something saying that the entire chromosome is not inactivated and that small segments can remain active which would explain XXY as you explained.

Thanks for the help. Do you know anything on the mechanism of colorblindness?

unfortunately no. All I know is the phenotype result. I don't know what actually causes the loss of function.

 

[Avery07]

unfortunately no. All I know is the phenotype result. I don't know what actually causes the loss of function.

Ok, I'll do some looking into that then. I'm pretty sure it's not to do with "good/bad" protein though.

Can you answer what you meant by localized line? Is that just to mean that a set of cells in a certain tissue all are derived from the same embryonic parent cell and thus should have the same X genes inactivated?

That answers a lot of the problems that seem to arise here but still doesn't account for the calico cat. Unless of course different lines affect different areas of the fur.

If you're not aware of the calico example, hair color is X linked. XBXB and XBY give a black coat, XbXb and XbY give a yellow coat, and XBXb give a calico coat.

 

[Avery07]

unfortunately no. All I know is the phenotype result. I don't know what actually causes the loss of function.

I've tried to find the mechanism for colorblindness but can't find a straight forward answer.

From what I can tell there are several different photoreceptors in a normal individual. Those having colorblindness lack one or more of these photoreceptors.

The photoreceptors themselves have different pigments which absorb light at different spectrums. In loosing one or more, you loose the ability to detect a specific wavelength of light and thus its color.

It looks like the photoreceptor is itself a cell and not a protein. So the mechanism is still murky to me.

If I got the right idea of your "localized" meaning-- than this would support something like that.

Ohhh genetics...

 

[UCB05]

Ok, I'll do some looking into that then. I'm pretty sure it's not to do with "good/bad" protein though.

Can you answer what you meant by localized line? Is that just to mean that a set of cells in a certain tissue all are derived from the same embryonic parent cell and thus should have the same X genes inactivated?

That answers a lot of the problems that seem to arise here but still doesn't account for the calico cat. Unless of course different lines affect different areas of the fur.

If you're not aware of the calico example, hair color is X linked. XBXB and XBY give a black coat, XbXb and XbY give a yellow coat, and XBXb give a calico coat.

I just meant that in certain parts of the body, a local group of cells might have teh same chromosome inactivated because they are all descendants from the one cell. this characteristic can be largely subjective to the particular tissue.

This seems to be the case in calico cats too, as the patches represent patches of cells that descended from one particular inactivated progenitor cell, vs another. I got that from below:
http://www.bio.miami.edu/dana/dox/calico.html
The root site is miami.edu. I would think it's somewhat credible