At least four times as many boys as girls are diagnosed with autism, a neurodevelopmental disorder that manifests within the first three years of life. Because autism is strongly genetic, and boys and girls share the vast majority of their genomes, the disorder’s male bias is puzzling. No common risk or protective factors have yet been identified on the sex chromosomes that could account for the dramatic difference in prevalence between the sexes. Several plausible genetic theories have been put forth, however. Boys and girls could be affected by the same genetic factors, but girls could require more, or stronger, genetic ‘hits’ to be affected. Alternatively, there may be factors encoded on the sex chromosomes that protect girls or put boys at risk. In some cases, genetic variants could affect boys and girls differently; ‘male autism’ and ‘female autism’ could, to some degree, have distinct origins. Lauren Weiss, of the University of California, San Francisco, and her colleagues are trying to uncover the genetic causes for sexual dimorphism in autism. Most autism studies to date have included a ratio of male to female participants that reflects the disorder’s prevalence meaning there are not enough female participants to make robust sex comparisons. Weiss’ team plans to recruit additional female participants to boost the statistical power of other autism genetic repositories, such as the Simons Simplex Collection and the Autism Genetic Resource Exchange. The researchers plan to use microarray technology to comb these samples for variations in DNA sequence and gene copy-number across the participants’ genomes. The team will then compare these variations between males and females to help prove or disprove the various genetic theories and identify sex-specific susceptibility genes. Weiss says that determining what protects girls from autism will be useful in understanding, and potentially reducing, the risk for boys. Currently, this project is in the recruitment phase, and is recruiting retrospectively and prospectively from autism, genetics and neurology clinics in the San Francisco area, and the Weiss team is in the process of establishing additional collaborations to achieve their recruitment goals.