Autism Spectrum Disorders: Analysis of Mobile Elements at 7q11.23 Williams-Beuren Region by Comparative Genomics

Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders, characterized by a deficit in social interaction and communication. Many genetic variants are associated with ASD, including duplication of 7q11.23 encompassing 26-28 genes. Symmetrically, the hemizygous deletion of 7q11.23 causes Williams-Beuren syndrome (WBS), a multisystem disorder characterized by "hyper-sociability" and communication skills. Interestingly, deletion of four non-exonic mobile elements (MEs) in the "canine WBS locus" were associated with the behavioral divergence between the wolf and the dog and dog sociability and domestication. We hypothesized that indel of these MEs could be involved in ASD, associated with its different phenotypes and useful as biomarkers for patient stratification and therapeutic design. Since these MEs are non-exonic they have never been discovered before. We searched the corresponding MEs and loci in humans by comparative genomics. Interestingly, they mapped on different but ASD related genes. The loci in individuals with phenotypically different autism and neurotypical controls were amplified by PCR. A sub-set of each amplicon was sequenced by Sanger. No variant resulted associated with ASD and neither specific phenotypes were found but novel small-scale insertions and SNPs were discovered. Since MEs are hyper-methylated and epigenetically modulate gene expression, further investigation in ASD is necessary.