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.
Highlights
The Autism Spectrum Disorders (ASDs, MIM: 209850) are a heterogeneous group of childhood diseases characterized by abnormalities in social behaviour and communication, as well as patterns of restricted and repetitive behaviors [1]
We developed the MAPCNVMIR programme to map all human miRNA genes from miRBase to 178 de novo Copy Number Variants (CNVs) from 192 autistic patients (‘‘autistic sample (APL) datasets’’, see Table S1)
By this computational analysis based on Monte Carlo simulations we found that in positive chromosomes (FDRadjusted p values v0:05, see Table 2 for details) there is a probability of less than 5% to find, by chance, a number of miRNA genes included in CNVs higher than that detected in patients
Summary
The Autism Spectrum Disorders (ASDs, MIM: 209850) are a heterogeneous group of childhood diseases characterized by abnormalities in social behaviour and communication, as well as patterns of restricted and repetitive behaviors [1]. Twin studies have demonstrated a much higher concordance rates for the disease in monozygotic twins (92%) than in dizygotic twins (10%) [3,4], indicating a strong genetic basis for autism susceptibility, supported by the presence of autistic features in several monogenic disorders (e.g., Fragile X syndrome, Tuberous sclerosis). Despite these progresses the identity of genetic factors still remains unknown in the majority of patients and it is likely, that overall, the causes of autism are more complex than previously thought involving an interaction of genetic, epigenetic and environmental factors all interfering with the normal course of neurodevelopment [5,6,7]. De novo or inherited CNVs were observed in 5–10% of idiopathic ASD cases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
