| Autism Spectrum Disorders (ASD) are multifactorial social cognitive impairments, affecting approximately 1% of the population, with a fourfold increased prevalence in males. Previous research has suggested a relationship between social functioning and the parent of origin of the X chromosome, which aligns with this preferential sex pattern. One candidate in elucidating the etiology of ASD is epigenetic DNA methylation alterations. Our methylation microarray screening of control males and females identified sex-specific DNA methylation patterns at the promoter of the non-coding RNA and adjacent BCL6 co-repressor (BCOR) loci at Xp11.4. Subsequent pyrosequencing of bisulfite converted DNA confirmed this difference by consistently exhibiting an average of close to 50% methylation in females and 90% in males at both loci. We propose that an isoform of BCOR is silenced in males by methylation and expressed in females from the paternal X, thus acting as a protective mechanism in females against autism. Assisted reproductive technology is being investigated as a possible source of epimutation at these loci in a subset of ASD individuals. |
