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Interesting. It sounds like they used cells from someone with Klinefelter's syndrome (XXY sex chromosomes) but I'm curious if a similar technique could be used

Interesting. It sounds like they used cells from someone with Klinefelter's syndrome (XXY sex chromosomes) but I'm curious if a similar technique could be used to generate male and female cells from any male (XY sex chromosomes). Does anyone on here have an idea of why they needed to start with cells derived from someone with "mosaic" Klinefelter's?

hammock 4y ago
Not a geneticist, but X is not female and Y is not male. Rather, XX is female and XY is male. To make XX from a single XY person would be to clone the X and I would guess would lead to unviability problems when the chromosomes are put to use Edit: for those downvoting, can you tell me how I’m wrong, if that is the case?
- deleted 4y ago
  [deleted]
- _Algernon_ 4y ago
  You're correcting a claim which wasn't made by the GP (Not sure if it has been edited though), as well as calling out that you're being downvoted which is against HN guidelines. >Please don't comment about the voting on comments. It never does any good, and it makes boring reading.
  - withinboredom 4y ago
    I’m pretty sure you’re the one commenting about voting. Their edit asks why they’re wrong and using the fact they are being downvoted to encourage people to reply. The replies since then have been interesting and not boring at all. Until I got to yours.
    - _Algernon_ 4y ago
      Fair enough
- bioemerl 4y ago
  I think it's because the person you're responding to didn't seem to be implying that a single X or a single y would count? Instead, they're probably talking about taking three cells with XY, and then using that to create an xx, an xy, and then some leftover parts. If that is the case, your correction might seem arrogant or assuming.
  - whimsicalism 4y ago
    Seems obvious to me why they led with that clarification and then directly responded to the point of why you might be able to make XX from XXY but not XY.
- nonameiguess 4y ago
  Also not a geneticist, but I'm pretty sure this is wrong because you only get recombination between analogous autosome pairs. The allosomes, or sex chromosomes, you just get from one parent anyway. Females get the X from the mother and the X from the father, but rather than recombination producing an X that is different from either parent, one of them just gets deactivated randomly in every cell during embryonic development and the offspring ends up with a single active X in each cell, usually roughly 50/50 split between exactly the same as the father and exactly the same as the mother. This is true in placental mammals, but in marsupials, it is always the father's X that gets deactivated. So it seems like making XX from a single XY person would just end up doing something genetically similar to what already happens with marsupials, which doesn't result in non-viability. Of course, cloning at all does result in not getting genetic diversity you would normally get from recombination, which can eventually result in population-level problems if you're doing enough of it.
  - adrian_b 4y ago
    The recombination happens when the gametes are produced, during meiosis. While in males there is no recombination between the X and Y chromosomes, in females sometimes there is recombination between the two X chromosomes. Therefore the X chromosome received by a child from the mother may either be 1 of the 2 X chromosomes of the mother, chosen randomly, or it may be a combination of those 2 X chromosomes. The inactivation of an X chromosome happens only in the female somatic cells, where the remaining active X chromosome is either the X chromosome of the father or 1 of the 2 X chromosomes of the mother or a combination of the 2 X chromosomes of the mother.
- bewaretheirs 4y ago
  My understanding is that the master switch for sex determination has been identified as the "SRY" gene normally found on the Y chromosome. Active SRY means development heads down the "male" path in the genes; no SRY (or non-functional SRY) means development heads down the "female" path. SRY can cross over to the X chromosome (resulting in an XX male), but the end result is usually sterile as there are other genes elsewhere on the Y chromosome that are also necessary for complete development.
- WalterBright 4y ago
  I suspect that making an XX from the same X would result in expression of all the recessive genes, which would be the ultimate in inbreeding. Probably with quickly fatal consequences.
  - deleted 4y ago
    [deleted]
  - shagie 4y ago
    Consider that in all males, all of the X chromosome genes are expressed. What's more, with X inactivation, one of the chromosomes in XX becomes almost completely inactive and all of the genes on the other chromosome are expressed. https://en.wikipedia.org/wiki/X-inactivation https://en.wikipedia.org/wiki/X-inactivation > X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a transcriptionally inactive structure called heterochromatin. As nearly all female mammals have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome (see dosage compensation).
    - thaumasiotes 4y ago
      > What's more, with X inactivation, one of the chromosomes in XX becomes almost completely inactive There is a huge distance between "almost completely inactive" and "inactive". A Turner's syndrome patient (only one X chromosome) usually has several obvious physical defects, including sterility. Interestingly, as far as I'm aware the things we usually think of as "X-linked" (more common in men, inherited as a recessive phenotype on the X chromosome - things like red/green colorblindness and male-pattern baldness) aren't as common in Turner's patients as you might expect.
- thaumasiotes 4y ago
  > for those downvoting, can you tell me how I’m wrong, if that is the case? Sure. Your claim that X is not female is correct. Your claim that Y is not male is wrong. Y is male. If one or more Y chromosomes are present, a male will develop, and if zero or fewer are present, a female will develop.[1] Cloning a normal male's single X chromosome would lead to the type of problems familiar from inbreeding, but would be unlikely to lead to nonviability; two different X chromosomes, which all normal women have, are already too many and parts of them must be inactivated so that normal development can proceed. The Y chromosome is unimportant enough that chromosomal abnormalities generally leave the organism in a viable, if often defective, state. The subject of this experiment is an example, with three (XXY) sex chromosomes. One X chromosome and no Y chromosomes (which would usually be described "XO", not "X") would get you a female with Turner syndrome. In a handy table: X alone: female, Turner syndrome Y alone: male, but nonviable; this will be a miscarriage. XX: female, normal XY: male, normal YY: male, nonviable XXX: female, triple X syndrome XXY: male, Klinefelter syndrome XYY: male, Jacobs syndrome YYY: male, nonviable [1] There is an exception related to androgen insensitivity. There you have a genetic male that develops into what is mostly a phenotypic female. Such people have female psychology and female external anatomy, but they do not have a female reproductive system and are therefore sterile.
  - psychphysic 4y ago
    Thanks nicely laid out.
jcampbell1 4y ago
This individual had T-cells that were: XX, XXY, and XY (mosaic Klinefelters), but otherwise genetically identical. They collected the XX and XY cells and coaxed them into being stem cells. Now researchers can use this stem cell line for research.
- skadamou 4y ago
  I see. So it was more about capturing the cells with the desired chromosomes and converting them to stem cells than about creating cells with the desired chromosomes. Thank you for your explanation!
anon291 4y ago
Doubtful. Males methylate their X chromosomes differently from females during the production of gametes.

hammock 4y ago

Not a geneticist, but X is not female and Y is not male. Rather, XX is female and XY is male. To make XX from a single XY person would be to clone the X and I would guess would lead to unviability problems when the chromosomes are put to use Edit: for those downvoting, can you tell me how I’m wrong, if that is the case?

deleted 4y ago
[deleted]
_Algernon_ 4y ago
You're correcting a claim which wasn't made by the GP (Not sure if it has been edited though), as well as calling out that you're being downvoted which is against HN guidelines. >Please don't comment about the voting on comments. It never does any good, and it makes boring reading.
- withinboredom 4y ago
  I’m pretty sure you’re the one commenting about voting. Their edit asks why they’re wrong and using the fact they are being downvoted to encourage people to reply. The replies since then have been interesting and not boring at all. Until I got to yours.
  - _Algernon_ 4y ago
    Fair enough
bioemerl 4y ago
I think it's because the person you're responding to didn't seem to be implying that a single X or a single y would count? Instead, they're probably talking about taking three cells with XY, and then using that to create an xx, an xy, and then some leftover parts. If that is the case, your correction might seem arrogant or assuming.
- whimsicalism 4y ago
  Seems obvious to me why they led with that clarification and then directly responded to the point of why you might be able to make XX from XXY but not XY.
nonameiguess 4y ago
Also not a geneticist, but I'm pretty sure this is wrong because you only get recombination between analogous autosome pairs. The allosomes, or sex chromosomes, you just get from one parent anyway. Females get the X from the mother and the X from the father, but rather than recombination producing an X that is different from either parent, one of them just gets deactivated randomly in every cell during embryonic development and the offspring ends up with a single active X in each cell, usually roughly 50/50 split between exactly the same as the father and exactly the same as the mother. This is true in placental mammals, but in marsupials, it is always the father's X that gets deactivated. So it seems like making XX from a single XY person would just end up doing something genetically similar to what already happens with marsupials, which doesn't result in non-viability. Of course, cloning at all does result in not getting genetic diversity you would normally get from recombination, which can eventually result in population-level problems if you're doing enough of it.
- adrian_b 4y ago
  The recombination happens when the gametes are produced, during meiosis. While in males there is no recombination between the X and Y chromosomes, in females sometimes there is recombination between the two X chromosomes. Therefore the X chromosome received by a child from the mother may either be 1 of the 2 X chromosomes of the mother, chosen randomly, or it may be a combination of those 2 X chromosomes. The inactivation of an X chromosome happens only in the female somatic cells, where the remaining active X chromosome is either the X chromosome of the father or 1 of the 2 X chromosomes of the mother or a combination of the 2 X chromosomes of the mother.
bewaretheirs 4y ago
My understanding is that the master switch for sex determination has been identified as the "SRY" gene normally found on the Y chromosome. Active SRY means development heads down the "male" path in the genes; no SRY (or non-functional SRY) means development heads down the "female" path. SRY can cross over to the X chromosome (resulting in an XX male), but the end result is usually sterile as there are other genes elsewhere on the Y chromosome that are also necessary for complete development.
WalterBright 4y ago
I suspect that making an XX from the same X would result in expression of all the recessive genes, which would be the ultimate in inbreeding. Probably with quickly fatal consequences.
- deleted 4y ago
  [deleted]
- shagie 4y ago
  Consider that in all males, all of the X chromosome genes are expressed. What's more, with X inactivation, one of the chromosomes in XX becomes almost completely inactive and all of the genes on the other chromosome are expressed. https://en.wikipedia.org/wiki/X-inactivation https://en.wikipedia.org/wiki/X-inactivation > X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a transcriptionally inactive structure called heterochromatin. As nearly all female mammals have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome (see dosage compensation).
  - thaumasiotes 4y ago
    > What's more, with X inactivation, one of the chromosomes in XX becomes almost completely inactive There is a huge distance between "almost completely inactive" and "inactive". A Turner's syndrome patient (only one X chromosome) usually has several obvious physical defects, including sterility. Interestingly, as far as I'm aware the things we usually think of as "X-linked" (more common in men, inherited as a recessive phenotype on the X chromosome - things like red/green colorblindness and male-pattern baldness) aren't as common in Turner's patients as you might expect.
thaumasiotes 4y ago
> for those downvoting, can you tell me how I’m wrong, if that is the case? Sure. Your claim that X is not female is correct. Your claim that Y is not male is wrong. Y is male. If one or more Y chromosomes are present, a male will develop, and if zero or fewer are present, a female will develop.[1] Cloning a normal male's single X chromosome would lead to the type of problems familiar from inbreeding, but would be unlikely to lead to nonviability; two different X chromosomes, which all normal women have, are already too many and parts of them must be inactivated so that normal development can proceed. The Y chromosome is unimportant enough that chromosomal abnormalities generally leave the organism in a viable, if often defective, state. The subject of this experiment is an example, with three (XXY) sex chromosomes. One X chromosome and no Y chromosomes (which would usually be described "XO", not "X") would get you a female with Turner syndrome. In a handy table: X alone: female, Turner syndrome Y alone: male, but nonviable; this will be a miscarriage. XX: female, normal XY: male, normal YY: male, nonviable XXX: female, triple X syndrome XXY: male, Klinefelter syndrome XYY: male, Jacobs syndrome YYY: male, nonviable [1] There is an exception related to androgen insensitivity. There you have a genetic male that develops into what is mostly a phenotypic female. Such people have female psychology and female external anatomy, but they do not have a female reproductive system and are therefore sterile.
- psychphysic 4y ago
  Thanks nicely laid out.

jcampbell1 4y ago

This individual had T-cells that were: XX, XXY, and XY (mosaic Klinefelters), but otherwise genetically identical. They collected the XX and XY cells and coaxed them into being stem cells. Now researchers can use this stem cell line for research.

skadamou 4y ago
I see. So it was more about capturing the cells with the desired chromosomes and converting them to stem cells than about creating cells with the desired chromosomes. Thank you for your explanation!

anon291 4y ago

Doubtful. Males methylate their X chromosomes differently from females during the production of gametes.