Blood RNA Sequencing Indicates Upregulated BATF2 and LY6E and Downregulated ISG15 and MT2A Expression in Children with Autism Spectrum Disorder

Abstract

Mutations in over 100 genes are implicated in autism spectrum disorder (ASD). DNA SNPs, CNVs, and epigenomic modifications also contribute to ASD. Transcriptomics analysis of blood samples may offer clues for pathways dysregulated in ASD. To expand and validate published findings of RNA-sequencing (RNA-seq) studies, we performed RNA-seq of whole blood samples from an Israeli discovery cohort of eight children with ASD compared with nine age- and sex-matched neurotypical children. This revealed 10 genes with differential expression. Using quantitative real-time PCR, we compared RNAs from whole blood samples of 73 Israeli and American children with ASD and 26 matched neurotypical children for the 10 dysregulated genes detected by RNA-seq. This revealed higher expression levels of the pro-inflammatory transcripts BATF2 and LY6E and lower expression levels of the anti-inflammatory transcripts ISG15 and MT2A in the ASD compared to neurotypical children. BATF2 was recently reported as upregulated in blood samples of Japanese adults with ASD. Our findings support an involvement of these genes in ASD phenotypes, independent of age and ethnicity. Upregulation of BATF2 and downregulation of ISG15 and MT2A were reported to reduce cancer risk. Implications of the dysregulated genes for pro-inflammatory phenotypes, immunity, and cancer risk in ASD are discussed.

High purity and integrity RNA from human cell lines stored in liquid nitrogen for over 20 years

“…RIN values were determined for all RNA samples from the three LCL cohorts ( N = 39; Table 1) by an automated electrophoresis process using the TapeStation system (Agilent). Additionally, we applied nucleic acid quantitation by using the Qubit™ RNA BR Assay Kit (Invitrogen™, Thermo Fisher Scientific) as described for a recent RNA‐seq project from our lab (Voinsky et al, 2022).…”

The Importance of Data Sources for Machine Learning Applications in Autism: A Mini Review

“…Feldner-Busztin et al 42 indicated the potential of the technologies while emphasizing the need to increase the sample size for each omics and the overall overlapping omics data per sample, namely the genomics, epigenomics, transcriptomics and metabolomics per sample. A range of analytical techniques are applied in several papers covering genomics 32 , RNA signature 30,43 , proteomics 29 , and metabolomics 25,28 . In particular, two high-level bioinformatics annotation engines (Gene Ontology: geneontology.org; and KEGG: www.genome.jp/kegg/) are applied across these patient-derived bioinformatics datasets to permit classification of genes, RNA, proteins and metabolites.…”

Nitrosative Stress in Autism: Supportive Evidence and Implications for Mitochondrial Dysfunction

“…Notably, in our recent RNA‐sequencing study of whole blood samples from 73 Israeli and American children with ASD compared with 26 matched neurotypically developing children, we observed reduced expression of MT2A , a gene coding for metallothionein 2A (FD = 0.72; p = 0.0057). [ 26 ] Metallothioneins play a key role in the detoxification of heavy metals and act as antioxidants, protecting cells against hydroxyl free radicals, including from neuronal damage by excessive NO. [ 27 , 28 , 29 ] It could therefore be that the reduced blood MT2A mRNA in children with ASD is implicated in the elevated tyrosine nitration of proteins, following peroxynitrite interaction with proteins, as observed by the Amal team.…”