American geneticists have discovered why autism spectrum disorders are diagnosed four to five times more often in men than in women: an active ZFX gene on the X chromosome softens the impact of harmful mutations and lowers the risk of severe manifestations of the disorder in women, the website infohub.kz reports.
Researchers at Boston Children's Hospital in the United States have uncovered the genetic mechanism behind a long-known phenomenon: the reduced vulnerability of the female body to autism spectrum disorders. In a paper published in the journal Nature, the scientists demonstrated that the gene for the transcriptional activator ZFX controls an entire network of genes associated with autism and mitigates the effects of harmful mutations in the female body.
Autism is detected four to five times more often in men than in women. Geneticists have long linked this to differences in the sex chromosomes, but the exact mechanism remained a mystery. In female cells, one of the two X chromosomes is usually inactivated to prevent cell death, but more than sixty genes escape this shutdown. These include ZFX, which continues to be fully expressed from both chromosomes at once. As a result, the activity level of this gene in women is substantially higher than in men, who have only a single X chromosome.
A team led by Professor Christopher Walsh, together with lead authors Rebecca Andersen and Maya Talukdar, studied gene activity using a model of human cells. They found that a mutation in just one gene triggers a cascading suppression of dozens of other DNA regions. The authors called this phenomenon transcriptomic convergence. High ZFX activity protects this gene network from large-scale failures.
According to Walsh, the discovery paves the way for fundamentally new therapeutic approaches. Instead of searching for drugs to target hundreds of rare mutations, scientists could stimulate ZFX activity, potentially improving the condition of both men and women with spectrum disorders.