Assessing the impact of copy number variants on miRNA genes in autism by Monte Carlo simulation

PLoS One. 2014 Mar 25;9(3):e90947. doi: 10.1371/journal.pone.0090947. eCollection 2014.


Autism Spectrum Disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies have investigated the role of de novo Copy Number Variants (CNVs) and microRNAs as important but distinct etiological factors in ASD. We developed a novel computational procedure to assess the potential pathogenic role of microRNA genes overlapping de novo CNVs in ASD patients. Here we show that for chromosomes # 1, 2 and 22 the actual number of miRNA loci affected by de novo CNVs in patients was found significantly higher than that estimated by Monte Carlo simulation of random CNV events. Out of 24 miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir-4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic subjects as reported in the Database of Genomic Variants. Altogether the results reported in this study represent a first step towards a full understanding of how a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in autism. We also propose that the procedure used in this study can be effectively applied to CNVs/miRNA genes association data in other genomic disorders beyond autism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / genetics*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 2 / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • Computer Simulation*
  • DNA Copy Number Variations / genetics*
  • Gene Regulatory Networks
  • Genetic Loci / genetics*
  • Genome, Human
  • Humans
  • MicroRNAs / genetics*
  • Monte Carlo Method*


  • MicroRNAs

Grant support

The authors acknowledge funding from University of Palermo and from the Italian Ministry of Health: “Ricerca corrente 2013” entitled: “Ritardo mentale, epilessia e autismo: studio genetico, clinico e neurofisiologico”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.