Mammalian X inactivation

(c) Hybrid Medical Animation

In humans, males are 46XY and females are 46XX. The Y chromosome has been in the news recently but we’re more concerned about the X chromosome today. You’ll notice that there are two copies of the X in human females – do we have double the X gene products? No, X inactivation silences most but not all of the genes on one of the two X chromosomes in mammalian females.

One X in each cell is turned off (inactive) through epigenetic changes; there are no changes to the DNA of the X chromosomes. This happens early in development and the same X is stays off through a lifetime of cell divisions. (Note: this is pretty cool and I studied how the inactive state is maintained through a woman’s lifetime with epigenetic markers.)

So both X chromosome are in all cells but the mother’s X chromosome works in some cells and the father’s copy works in others. The two types of cells can have different alleles (versions) of the genes so they may function differently. One obvious manifestation is calico cats where the black colour is on one chromosome and the orange is on another, leading to different coloured patches. It is also important for X-linked diseases such as Fragile X syndrome (developmental delay) and hemophilia (blood disorder). Males only get one X chromosome and if they inherit a gene that doesn’t produce Factor VIII, they will have Hemophilia A. Females have two X chromosomes so some of their blood cells won’t produce Factor VIII (mutated version) and some will (normal version) and on balance, she will produce enough Factor VIII to prevent Hemophilia A.

More than one X?

Two sets of MY chromosomes – one metaphase and one interphase

All X chromosomes above one in a cell undergo X inactivation. That means that a male with 46 XXY (Klinefelter’s Syndrome) will still only have one X active in each cell. When we did each other’s chromosomes in the lab, my partner had 4 X chromosomes = 48XXXX. I thought I had done something wrong but it was confirmed by better lab techs 🙂 She did not seem to have any ill effects despite there being reports of symptoms. We might find that extra chromosomes are more common if we karyotyped everyone. (I’m boring 46XX.)

Note: I studied X inactivation for my PhD and I was surprised at how hard it was for me to write this piece. I have a patter that I used in high schools but it doesn’t seem fancy enough for writing. Interesting process to write things down.