title: Assessing the impact of copy number variants on miRNA genes in autism by Monte Carlo simulation.
abstract: 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.
authors.affiliation: Dipartimento di Fisica e Chimica, Università di Palermo, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marrale
authors.affiliation: Dipartimento di Fisica e Chimica, Università di Palermo, Palermo, Italy.
authors.forename: Nadia Ninfa
authors.initials: NN
authors.lastname: Albanese
authors.affiliation: U.O.C. di Genetica Medica Laboratorio di Genetica Molecolare, Associazione Oasi Maria SS. (I.R.C.C.S.), Troina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Calì
authors.affiliation: Dipartimento di Fisica e Chimica, Università di Palermo, Palermo, Italy; U.O.C. di Genetica Medica Laboratorio di Genetica Molecolare, Associazione Oasi Maria SS. (I.R.C.C.S.), Troina, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Romano
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003198:Computer Simulation; D056915:DNA Copy Number Variations / Q000235:genetics*; D053263:Gene Regulatory Networks; D056426:Genetic Loci / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009010:Monte Carlo Method
chemical_list: D035683:MicroRNAs