Genetic etiologies of Autism Spectrum Disorders (ASD) are complex, and genetic factors identified so far are very diverse. In complex genetic diseases such as ASD, de novo or inherited chromosomal abnormalities are valuable findings for researchers in identifying the underlying genetic risk factors. With gene mapping studies on these chromosomal abnormalities, dozens of genes have been associated with ASD and other neurodevelopmental genetic diseases, so far. In this study, we aimed to find the causative genetic factors in patients with ASD that have apparently balanced chromosomal translocation in their karyotypes.
For mapping the broken genes due to chromosomal translocations we performed whole genome DNA sequencing with HiSeq X (Illuminina®) platform at 30X depth. Chromosomal breakpoints and large DNA copy number variations (CNV) were determined with delly and svABA tools after genome alignment. Identified CNVs and single nucleotide variations (SNV) were evaluated with VCF-BED intersect and Gemini tools on the galaxy platform, respectively. Targeted resequencing approach was performed on JMJD1C gene in all ASD cohorts of us (220 patients) by Illumina’s Miseq® platform. For molecular modeling we used homology modelling approach by SWISS-MODEL.
We found that there was not any contribution of the broken genes or regulator DNA sequences to ASD, whereas the SNVs on JMJD1C, CNKSR2 and DDX11 genes were the most convincing genetic risk factors for underlying ASD phenotypes.
Genetic etiologies of ASD should be analyzed comprehensively by taking in to account of the all chromosomal structural abnormalities and de novo or inherited CNV/SNVs with all possible inheritance patterns.