Skewed X-chromosome inactivation: females affected by autoimmune diseases more often than men

X-chromosome inactivation (XCI) occurs in females to balance the information from the maternal and paternal X-chromosomes. In most instances, it works out to about half the cells in the female expressing the paternal X and the other half the maternal X. However, in some cases skewed XCI can occur resulting in an unbalanced expression from one parental X chromosome.

An autoimmune disease is when your body attacks itself, like your lymphocytes attacking your joints or thyroid gland. This happens far more often in females than males, possibly because of skewed XCI. In this study, researchers extracted and analysed DNA from blood lymphocytes to determine if there was a significant prevalence of skewed XCI in patients with rheumatoid arthritis and autoimmune thyroid disease relative to a control group. What if key immune system cells in a female body were expressed at a skewed rate, for example, 80% from the maternal X-chromosome but only 20% from the paternal chromosome, leading the cells to tolerate other cells expressing the maternal chromosome but more likely to attack the cells expressing the less familiar paternal X-chromosome?  This takes domestic quarrels to a whole new level…



Jennifer Goddard