ZFX gene and autism sex difference, Digi Mart USA News: Autism is diagnosed in boys around three to four times as often as in girls, a gap that has puzzled researchers because autism-associated genes are not confined to one sex. A study led by researchers from Boston Children’s Hospital in the United States, as reported by New Atlas and Phys.org, points to a single gene that may help explain the difference.
The researchers grew lab-cultured progenitor cells, which precede the development of neurons, and reduced the activity of several individual autism-associated genes. Different disruptions repeatedly lowered activity in other autism-linked genes, with 27 further genes becoming less active in at least 10 of the experiments.
Follow-up experiments using brain organoids, small clumps of lab-grown tissue, supported this pattern.
Mapping these regulatory relationships identified ZFX, a “zinc finger transcription factor gene” on the X chromosome that encodes a protein helping to activate other genes, including many linked to autism. In most cells, genes on one of the two X chromosomes are naturally switched off, but ZFX is a notable exception and typically stays active on both copies.
The researchers suggest this higher baseline expression in female brains could help maintain activity across the network when other genes are disrupted.
The Y chromosome has a similar gene, ZFY, but the report says its effect as an activator of other genes is weaker, which could partly account for the sex difference. The researchers also reanalysed existing gene-expression data from donated brain tissue and found evidence of reduced ZFX activity in excitatory neurons from autistic males.
The findings are consistent with the female protective effect hypothesis, supported in part by a 2014 genetic study suggesting women may need to carry more autism-related genes before showing the condition. However, the report notes the experiments used a single male-derived stem-cell line, so comparisons between male and female cells are needed.
Other explanations, including diagnostic bias, camouflaging, steroid hormone activity and environmental exposures, have not been ruled out.
The research received a postdoctoral fellowship from Autism Speaks, an organisation whose history has drawn criticism from some neurodiversity advocates. Autism Speaks says it no longer supports research seeking a cure.
The article is based on a publisher report and has not been independently verified.
