5 January 2018 (Saturday) - The Lyon Hypothesis...

Whilst looking at blood films I saw a neutrophil drumstick. I knew what they were... once. So I looked it up and started quite a little voyage of discovery. 

The Internet told me that a neutrophil drumstick is a nuclear lobule attached by a slender strand to the nucleus of some polymorphonuclear leukocytes of normal females but not of normal males. They contain  the Barr body. Barr body...?
"a small, densely staining structure in the cell nuclei of females, consisting of a condensed, inactive X chromosome. It is regarded as diagnostic of genetic femaleness"
But that just raised more questions.
Inactive X chromosome... Why is any chromosome inactive, X or otherwise. It turns out that if one of the X chromosomes isn't inactivated in females they will have twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome. Obvious really when you think about it.
Apparently the choice of which X chromosome will be inactivated is random in humans and all placental mammals (but not in marsupials… but I digress), but once an X chromosome is inactivated it will remain inactive throughout the lifetime of the cell and its descendants in the organism.

This suggests why you can see, that there are two red cell populations of erythrocytes: deficient cells and normal cells  in the blood of women heterozygous for Glucose-6-phosphate dehydrogenase (G6PD) deficiency, depending on whether the inactivated X chromosome (in the nucleus of the red cell's precursor cell) contains the normal or defective G6PD allele.

However, sometimes the X-inactivation isn't entirely random. It can be skewed toward the paternal or maternal X chromosome
This explains why although X-linked, approximately one third of patients with congenital sideroblastic anaemia  are women due to skewed X-inactivation

One lives and learns...

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