AIS mothers

[melonade]

I've had a curious question about how being an AIS carrier (mother) works. But it's not a question I've seen covered anywhere, so I need to ask known CAIS women themselves.

The way AIS is supposed to work is a mutation on the X chromosome which by a series of molecular changes renders the androgen receptors non-functional. And that the Y chromosome contains no copy of the AR gene to stop that from happening.

While in the carrier mother, the second X's copy of a good AR gene is supposed to override the AIS AR gene. But when the mother was born, one of her X chromosomes would be picked at random to be completely inactivated and become a Barr body. I can't find anything that gives a reason for why the inactivated X should be the AIS X.

So is it that 50 percent of the time, the AIS carrying mother should also have androgen insensitivity that no one cares about because she's female anyway? It should be easy to find out, because a non-androgen insensitive woman should at least have some peach fuzz somewhere on her at some point in her life.

So knowing what your mothers look like, can anyone say if they seemed reasonably androgen insensitive?

And if no AIS mothers are insensitive, then what is the biological force that makes sure the inactivated X is always the AIS X?

[miriam]

The generic genetic stuff:
http://www.aissg.org/21_OVERVIEW.HTM#GeneticsAIS

The specialist stuff:

Timing
All mouse cells undergo an early, imprinted inactivation of the paternally-derived X chromosome in two-cell or four-cell stage embryos.[4] The extraembryonic tissues (which give rise to the placenta and other tissues supporting the embryo) retain this early imprinted inactivation, and thus only the maternal X chromosome is active in these tissues.

In the early blastocyst, this initial, imprinted X-inactivation is reversed in the cells of the inner cell mass (which give rise to the embryo), and in these cells both X chromosomes become active again. Each of these cells then independently and randomly inactivates one copy of the X chromosome. This inactivation event is irreversible during the lifetime of the cell, so all the descendants of a cell which inactivated a particular X chromosome will also inactivate that same chromosome. This leads to mosaicism if a female is heterozygous for an X-linked gene, which can be observed in the coloration of calico cats. For an individual cell or lineage the inactivation is therefore skewed or 'non-random' this can give rise to mild symptoms in female 'carriers' of X-linked genetic disorders [5]

X-inactivation is reversed in the female germline, so that all ova contain an active X chromosome.

http://en.wikipedia.org/wiki/Lyonization



So knowing what your mothers look like, can anyone say if they seemed reasonably androgen insensitive?

No. My mother and my non-AIS sister have almost no pubic hair or armpit hair. But there are also mothers and non-ais sisters who have 'normal' pubic hair. (What the heck is 'normal'?). A mother who is a carrier can also get non-ais daughters and non-ais sons and they have 'normal' pubic hair too.

And if no AIS mothers are insensitive, then what is the biological force that makes sure the inactivated X is always the AIS X?
As you can read in Wikipedia there is no such force.

Groeten, Miriam

[The Female Eunuch]

Quote:And if no AIS mothers are insensitive, then what is the biological force that makes sure the inactivated X is always the AIS X?
MiriamAs you can read in Wikipedia there is no such force.

But the bit you posted from Wikipedia is about mice. In a human, the same X is inactivated in every cell.

cheers,
Caroline

[fraulein_Maria]

[QUOTE=The Female Eunuch;16913]
But the bit you posted from Wikipedia is about mice. In a human, the same X is inactivated in every cell.

cheers,
Caroline

>>> are you quite sure? mice are not used for comparison because they closely resemble humans (pigs are MUCH closer ;) but because its cheaper to do research with them as models.

[melonade]

The generic genetic stuff:
http://www.aissg.org/21_OVERVIEW.HTM#GeneticsAIS

The specialist stuff:






No. My mother and my non-AIS sister have almost no pubic hair or armpit hair. But there are also mothers and non-ais sisters who have 'normal' pubic hair. (What the heck is 'normal'?). A mother who is a carrier can also get non-ais daughters and non-ais sons and they have 'normal' pubic hair too.


As you can read in Wikipedia there is no such force.

Groeten, Miriam

Thank you Miriam, that was very informatiive. What you are saying about how some mothers are less hirsuit than normal while others are normal does agree with my thought that maybe 50 percent of the carrier mothers would express their AIS X. That doesn't necessarily conflict with having uneffected sisters. Only 50 percent would get an AIS X from their carrier mother, only 50 percent of the 50 percent carriers would express it. If nothing prevents it, then it must happen to someone.

[fraulein_Maria]

My mother and my non-AIS sister have almost no pubic hair or armpit hair.

>>> so although they are known carriers, but not AIS'ers (either C or P) this sign of local tissue androgen insensitivity is no indicator of carrier status? <<

But there are also mothers and non-ais sisters who have 'normal' pubic hair.

>>> that may be so, but there are other tissues that might be affected besides hair follicles. it could be said that i am androgen insensitive in the beard region; asiatics of BOTH genders often are. But it would be a mistake to then assume that other tissues were insensitive also ;)

Perhaps the carriers with pubic and accillary hair might have.... a low red cell count... because there bone marrow which in everyone else is androgen sensitive... is not.

XX CAH's have a high red cell count in comparison to there "normal" sisters, as do XX CAH carriers, because the production rate of them is DIRECTLY related to blood levels of testosterone, and sensitivity to it.

In regards to AIS'ers this is obviously conjecture on my part, but i hope i have given you interesting thoughts. :) <<<

As you can read in Wikipedia there is no such force.

>>> i would venture to say that if any such force existed, it would simply be the tendency of self-replicating and self-repairing systems to function. the primordial immune system ensuring that primordial replication accurately takes place. <<<

[The Female Eunuch]

Maria wrote: >>> are you quite sure? mice are not used for comparison because they closely resemble humans (pigs are MUCH closer but because its cheaper to do research with them as models.

how does the fact that mice are genetically less like us than pigs are conflict with the idea that the switching off of X chromosomes in humans happens differently from how it does in mice?

surely, if anything, our genetic difference from mice makes it more likely that we would deal with extra X-chromosomes differently from how mice do?

[fraulein_Maria]

[QUOTE=The Female Eunuch;16928]Maria wrote:

how does the fact that mice are genetically less like us than pigs are conflict with the idea that the switching off of X chromosomes in humans happens differently from how it does in mice?

surely, if anything, our genetic difference from mice makes it more likely that we would deal with extra X-chromosomes differently from how mice do?

>>> my apologies. i mis-understood. i thought you were saying the opposite.

[The Female Eunuch]

Maria wrote:>>> my apologies. i mis-understood. i thought you were saying the opposite.

Thanks. So if we agree that in XX humans every cell in the body has the same X chromosome switched off, then I'm pretty certain we still haven't answered the question of why an XX woman with one AIS X-chromosome cannot have androgen insensitivity.

I'd still be interested to know.

Oh, and Thank you Miriam for posting that AISSQ URL. It didn't answer this question, but led me to some other interesting stuff (including an example of a transsexual group trying to hijack intersex concerns).

cheers,
Caroline

[miriam]

But the bit you posted from Wikipedia is about mice. In a human, the same X is inactivated in every cell.


No, it's not about mice. The part I quoted refers to an article by Puck and Willard published in the New England Journal of Medicine in 1998 : X inactivation in females with X-linked disease.

X-linked recessive disorders affect males, whereas female carriers are generally spared. This is due in part to the random inactivation in females of one of the two X chromosomes in all somatic cells. Normal females are thus a mosaic of two cell populations, each expressing the alleles from one X chromosome or the other. Thus, in female carriers of an X-linked mutation, approximately 50 percent of cells on average have the normal allele on the active X chromosome (with the mutant allele being on the inactive X chromosome), and these functionally normal cells are generally sufficient to spare females from . .

https://content.nejm.org/cgi/content/extract/338/5/325





http://www.ncbi.nlm.nih.gov/pubmed/9445416


This is what I remember from school... In the early emale zygote BOTH x-chromosomes are active. This changes when there are, let's say, 5000 cells. In every cell one randomly chosen X-chromosomes is deactivated and after that the patern of active and inactive X-chromosomes does not change anymore. This means you can't say the same X is inactivated in every cell.

The word 'inactivated' is a bit inaccurate as about 10 to 15 percent of the genes on the inactivated remain avtive. BTW, this is comparable to the number of active genes on the Y-chromosome.

Sometimes there is also a strong tissue specific selection, but that's another story... Now I've to go back to work. :wink_smil

Groeten, Miriam

[The Female Eunuch]

So if we agree that in XX humans every cell in the body has the same X chromosome switched off,

sorry, I was wrong. I'm not sure where I got the idea that the switch-off in humans happened before the cells started dividing, but I've checked and confirmed that I was wrong and that it happens exactly the same way as in mice.

cheers,
Caroline

[Tom/Ms.G]

Is there a PAIS forum here? We are currently mentors to a young couple who have a PAIS child. They managed to circumvent the surgeons from "normalizing" their child but they could sure do with some support from parents and or PAIS adults.
Tom/Ms.G

[roguekiwixxy]

No. My mother and my non-AIS sister have almost no pubic hair or armpit hair. But there are also mothers and non-ais sisters who have 'normal' pubic hair. (What the heck is 'normal'?). A mother who is a carrier can also get non-ais daughters and non-ais sons and they have 'normal' pubic hair too.


As you can read in Wikipedia there is no such force.

Groeten, Miriam

Hi MIraim, is it ok for me to ask a question here?

I can't find a reference of AIS beiong inherited so do you have any information about that?

[miriam]

http://androgendb.mcgill.ca/

http://androgendb.mcgill.ca/map.gif

http://aissg.org/21_OVERVIEW.HTM#GeneticsAIS


Something like this?

Groeten, Miriam

[roguekiwixxy]

http://aissg.org/21_OVERVIEW.HTM#GeneticsAIS


Something like this?

Groeten, Miriam


Yeup, that one is perfect. Now I know. Someone should go tell the authors of the "KInsey New Reort on Sex" toget their facts right, but I tried with their Klinefelter /XXY stuff and thyey just ignored me! Typical.

[roguekiwixxy]

This is what I remember from school... In the early emale zygote BOTH x-chromosomes are active. This changes when there are, let's say, 5000 cells. In every cell one randomly chosen X-chromosomes is deactivated and after that the patern of active and inactive X-chromosomes does not change anymore. This means you can't say the same X is inactivated in every cell.
Groeten, Miriam

So Miriam, when you get back from work, can you think about how that system might work in the case of XXY's?

See, some XXY's are mentally retarded, but not all, in fact the vast majority are not, that's just XXY's though, when you start thinking about XXYY's or XXXY's or XXXXY's things are different.

And can I have your consent to post this information at XXYTALK for the mothers?

[miriam]

So Miriam, when you get back from work, can you think about how that system might work in the case of XXY's?

See, some XXY's are mentally retarded, but not all, in fact the vast majority are not, that's just XXY's though, when you start thinking about XXYY's or XXXY's or XXXXY's things are different.

The word 'inactive' should be read as 'partial inactive'. After inactivation quite a few genes on the X-chromosomes remain active. Actually, one of the genes that escapes inactivation is the Androgen receptor gene (AR). I'm not an expert on KS but I happen to know that at least two articles have been published about the relationship between the AR gene and KS:

Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E 2004
X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients.
J Clin Endocrinol Metab 89:6208-6217


Zinn AR, Ramos P, Elder FF, Kowal K, Samango-Sprouse C, Ross JL 2005
Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter) syndrome.
J Clin Endocrinol Metab 90:5041-5046


And can I have your consent to post this information at XXYTALK for the mothers?

Sure!

Groeten, Miriam