Copy Number Variants and microRNAs in Autism Spectrum Disorders: a whole-genomeanalysis

In recent years, there has been an increased interest by the scientific community on Autism SpectrumDisorders (ASDs), neurodevelopmental disorders of childhood with an incidence of about 1/160 children [1].Different studies have indicated a strong genetic basis for autism susceptibility, also supported by thepresence of autistic features in several monogenic disorders (e.g.,Fragile X syndrome, Tuberous sclerosis).Since 2007 Copy Number Variants (CNVs) were recognized as important genetic factors in ASD [2].Studies performed so far have highlighted the pathogenic role of CNVs in terms of dosage change forprotein-coding genes and few works have suggested the potential involvement of miRNA on thepathogenesis of ASD [3]. Here, a novel computational procedure based on Monte Carlo randomization [4]was developed and applied to several published datasets to assess the potential pathogenic role ofmicroRNA genes overlapping de novo Copy Number Variants (CNVs) in patients with autism spectrumdisorders. Our results include the identification of 46 miRNA genes overrepresented in de novo CNVs fromseveral chromosomes and we propose that at least 7 miRNAs from the latter group are likely to play apathogenic role in autism. Moreover, the procedure used in this study can be effectively applied toCNV/miRNA data in other genomic disorders beyond ASD.