Whole genome analysis of dizygotic twins diagnosed with 'non-syndromic' autism spectrum disorder and their parents

Background: The availability of New Generation Sequencing (NGS) methods which cost is getting smaller day by day, have increasing for the investigation of genetic causes of complex and heterogeneous etiology of some diseases such as Autism Spectrum Disorder (ASD). In this study, identification of autism etiology in cases affected by genomic and transcriptomic evaluation of multiplex families; as well as the severity of the disorder and the characteristics of the individual and the results of these data. Besides this, it is planned to obtain high output data which will be a source for future researches. Method: Patients, who are followed at the Dokuz Eylul University School of Child and Adolescent Mental Health Department outpatient clinic, and who are total of 12 people, including 3 dizygotic twins with ASD according to DSM-5 criteria and their parents were included in the study. Patients with any syndrome were excluded. ASD diagnoses in the study of both twins affected the Childhood Autism Rating Scale (CARS) were applied. Autism Behavior Checklist related to the children of parents in the study (ABC) were asked to fill out the scale. Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL) all children and their families for a semi-structured interview with school age were enrolled in the study shall apply. Structured clinical DSM-IV for parents to assess whether the study is the diagnosis of Schizophrenia (SCID-I: Structured Clinical Interview for the DSM-IV Axis I Disorders) scale will be applied. Autism-Spectrum Quotient (ASQ) of its own self-report questionnaires from parents in the study will be asked to fill out to utilize Broad Autism Spectrum. Patients and parents DNA and RNA obtained from blood, Whole genome sequencing (WGS) and RNA sequencing (RNA-seq) methods were applied. Bioinformatics analysis of data and scale results were interpreted together. Results: When all the data were evaluated together, possible pathogenic candidate variants were identified for the cases. In only one case, the candidate variant was markedly less defined, and it was noted that transcriptomic analyzes of this phenomenon were also different from other participants. Functional analysis of transcriptomic data revealed that mitochondrial related genes were found to play a role. Conclusion: WGS is a comprehensive and benefical method of exploring genetic etiology of a disorder with heterogeneous and complex etiopathogenesis such as OSB. RNA-seq may also be useful candidate in future for identification of endogenous phenotypes and fort he prevention of impairment these comprensive data obtained by these methods provide a rich resource for many researches. Keywords: Autism spectrum disorder, Broad autism phenotype, twin studies, genomics, transkriptomics, Whole genome sequencing, Whole RNA sequencing, bioinformatics.