What is X-inactivation and why is it important?
X-inactivation is a process that occurs in the nuclei of all female mammals, due to them having two X chromosomes. Two X chromosomes is more than is really necessary in the mammal genome, as evidenced by the fact that 50% of the population (the males) is surviving perfectly well with only one. In order to prevent the overproduction of X-chromosome products, which could cause serious problems, each cell in a female mammal needs to silence one of their X chromosomes.
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In marsupials, it is always the paternal copy of the X chromosome that is inactivated, whereas placental mammals (non-marsupials) inactivate one X chromosome in each cell at random at a very early stage of development. The inactivated X becomes coated in an RNA product called Xist, or ‘X-inactive specific transcript’, triggering its condensation down into a dense ‘Barr body’. The Barr body is silenced by packaging into repressive heterochromatin, a form of DNA storage which inhibits transcription of genes.
Which X will be inactivated in each cell is decided in the early embryo. The descendants of these cells always inactivate the same copy of the X chromosome, creating distinct populations of cells. For a visualisation of the size of these populations, examine a tortoiseshell cat; the genes encoding coat colour in cats are on the X chromosome – the tortoiseshell pattern is produced by separate populations of cells producing black and orange pigments, depending on which X chromosome is active. This means that all female mammals are effectively genetic mosaics, and explains why females are usually less severely affected by genetic disorders carried on the X chromosome; if their other X chromosome doesn’t also carry the mutation, then only half of their cells will be affected by the condition. This also explains why the symptoms of people with multiple X chromosomes are much less severe than would be expected – all but one of their X chromosomes are usually inactivated.
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