Autism spectrum disorder is a complex developmental condition which affects the way a person communicates, learns, and interacts with others. Studies suggest that the ratio of autism in males to females ranges from 2:1 to 16:1, although the most-up-to-date estimate is 3:1.
In the past, it was believed that autistic people were mostly males, and it happens very rarely in females. This is actually very wrong, and it is also important that autistic women and girls receive a diagnosis for their condition.
How Do Women Inherit Autism?
Every female inherits two copies of the X chromosome, one from each parent. Since cells do not need two copies, the cells inactivate one copy early in embryonic development in a process known as X chromosome inactivation.
Because of this inactivation, every female possesses a mixture of cells, some containing an active X chromosome from the father and some from the mother. This phenomenon is known as mosaicism.
For decades, it was believed that mosaicism was random and would result in approximately 50/50 mixture of cells, with 50% containing an active paternal chromosome and 50% containing an active maternal X chromosome.
Reducing Autism With X Chromosome Inactivation
In a new mouse brain study, scientists discovered that this is not the case. Instead, there seems to be a bias in the process which leads to the paternal X chromosome being inactivated in 60% of the cells rather than the assumed 50%.
The study discovered that while the X-linked mutation that causes most autism cases is inherited from the father, the pattern of X-chromosome inactivation in the brain of women can avoid the effects of that mutation. Further details of the study are described in the paper "Distributed X chromosome inactivation in brain circuitry is associated with X-linked disease penetrance of behavior."
Led by Dr. Pavel Osten from Cold Spring Harbor Laboratory in New York, the research team first determined the ratio of X chromosome inactivation in healthy mice by studying 40 million brain cells per animal. This was done using high-throughput volumetric imaging and automated counting. The procedure revealed a systematic 60:$0 ratio across all possible anatomical areas.
The scientists then examined what would happen if they introduced a dangerous mutation into the X chromosomes. The fragile X syndrome was used as a mouse model for the mutation. This condition is regarded as the most common form of inherited intellectual and developmental disability in humans.
It was found that the mice with inherited mutation on their mother's X chromosome are less likely to be inactivated in the 60:40 ratio and are also more likely to exhibit behavior that resembles fragile X syndrome. They show more signs of less sociability, anxiety, deficits in sensorimotor function, and poor performance in spatial learning.
Meanwhile, the mice that inherited the mutation from one of their paternal X chromosomes were more likely to be inactivated and did not appear impaired. This finding suggests that the 20% difference in mutant X-active cells resulting from the bias can be protective against X mutations from the father.
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