Alternative splicing and gene co-expression network-based analysis of dizygotic twins with autism-spectrum disorder and their parents

Okay K., Varis P. U., Miral S., Ekinci B., Yaras T., KARAKÜLAH G., ...More

GENOMICS, vol.113, no.4, pp.2561-2571, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 113 Issue: 4
  • Publication Date: 2021
  • Doi Number: 10.1016/j.ygeno.2021.05.038
  • Journal Name: GENOMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.2561-2571
  • Keywords: Autism, Autism spectrum disorder, Alternative splicing, Co-expression networks, RNA-sequencing, Twin, FATTY-ACID COMPOSITIONS, CHILDREN, EXPRESSION, PROTEIN, TRANSCRIPTOME, PATHOGENESIS, DYSFUNCTION, INTEGRATION, MUTATIONS, INSIGHTS
  • Dokuz Eylül University Affiliated: Yes

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high heritability, however, understanding the complexity of the underlying genetic basis has proven to be a challenging task. We hypothesized that dissecting the aberrations in alternative splicing (AS) and their effects on expression networks might provide insight. Therefore, we performed AS and co-expression analyses of total RNA isolated from Peripheral Blood Mononuclear Cells (PBMCs) of two pairs of dizygotic (DZ) twins with non-syndromic autism and their parents. We identified 183 differential AS events in 146 genes, seven of them being Simons Foundation Autism Research Initiative (SFARI) Category 1-3 genes, three of which had previously been reported to be alternatively spliced in ASD post-mortem brains. Gene co-expression analysis identified 7 modules with 513 genes, 5 of which were SFARI Category 1 or Category 2 genes. Among differentially AS genes within the modules, ZNF322 and NR4A1 could be potentially interesting targets for further investigations.