Analysis of a Protein Network Related to Copy Number Variations in Autism Spectrum Disorder Jaqueline B. Schuch 1 & Vanessa R. Paixão-Côrtes 2 & Dânae Longo 3 & Tatiana Roman 1 & Rudimar dos S. Riesgo 4 & Josiane Ranzan 4 & Michele M. Becker 4 & Mariluce Riegel 1,5 & Lavinia Schuler-Faccini 1,5 Received: 1 July 2018 /Accepted: 22 May 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder, with strong genetic influences as evidenced by its high heritability. Submicroscopic variations (ranging from one kilobase to several megabases) in DNA, called copy number variations (CNVs), have been associated with psychiatric diseases, including ASD. We aimed to identify CNVs in children diagnosed with idiopathic ASD. We used microarray-based comparative genomic hybridization analysis to detect the CNVs, and bioinformatic tools to evaluate their pathogenic potential, based on predicted functional aspects. Using combined cytogenetic and bioinformatic tools, we identified an autism network of genes/proteins related to the CNVs. Among the 40 children analyzed, we found 14 potentially pathogenic CNVs, including those previously associated with ASD (located at 16p11.2, 15q11.2, and 7p21 regions). We suggest that the most relevant biological process and functional attributes involve olfactory receptors. The CNV-related autism network comprised 90 proteins and 754 nodes and indicated the family of olfactory receptors as a significant pathway in ASD. Olfactory receptors were previously associated with neurologic diseases, and they are possibly related to cognition. This integrative analysis that combines cytogenetics and bioinformatics is a promising approach to understand complex conditions such as ASD. Keywords ASD . CNV . Array-CGH . Bioinformatics . Olfactory receptor Introduction Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social impairments, communication deficits, and repetitive and re- stricted patterns of behavior. Despite the remarkable pheno- typic heterogeneity among patients with ASD, some symp- toms and comorbidities are common in most individuals af- fected, specially mood instability, aggression (self-directed and/or toward others), seizure episodes, echolalia, epilepsy, and sleep disorders (Levy et al. 2009; Newschaffer et al. 2007). The estimated prevalence is 1 in 68 children, with a male:female prevalence ratio of 4:1 (CDC 2014). Twin studies indicate heritability estimates of approximately 80% for ASD, implying a high genetic influence on this disorder (Ronald and Hoekstra 2011). On the other hand, Hallmayer et al. (2011) suggested that this index is overestimated and that the ASD heritability would be about 38%. Nevertheless, approximately 15% of ASD cases are associated with recognizable genetic causes, including genetic syndromes and other chromosomal abnormalities (Betancur 2011). Common and rare variants identified in association and genome scan studies seem to explain most of the idiopathic cases of ASD, adding pieces to the genetic puzzle of ASD (Anney et al. 2012). Also, exome studies (Chahrour et al. 2012; Cukier et al. 2014; Sanders et al. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-019-01343-7) contains supplementary material, which is available to authorized users. * Jaqueline B. Schuch jaqbs.bio@gmail.com 1 Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil 2 Department of General Biology, Instituto de Biologia, Universidade Federal da Bahia, Salvador, Brazil 3 Instituto Federal Farroupilha, Campus Alegrete, Alegrete, Brazil 4 Neuropediatrics Service, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil 5 Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Journal of Molecular Neuroscience https://doi.org/10.1007/s12031-019-01343-7