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

Irena Voinsky, Yazeed Zoabi, Noam Shomron, Moria Harel, Hanoch Cassuto, Joseph Tam, Shannon Rose, Adrienne C. Scheck, Mohammad A. Karim, Richard E. Frye, Adi Aran*, David Gurwitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageAmerican English
Article number9843
JournalInternational Journal of Molecular Sciences
Issue number17
StatePublished - Sep 2022

Bibliographical note

Funding Information:
The study was supported by a grant from the Israel-United States Science Foundation (BSF grant 2019049) to D.G., R.E.F. and S.R. In addition, I.V. was supported by a Ph.D. scholarship from the Yoran Institute for Human Genome Research at Tel Aviv University.

Publisher Copyright:
© 2022 by the authors.


  • RNA sequencing
  • autism spectrum disorder (ASD)
  • cancer
  • real-time qPCR


Dive into the research topics of 'Blood RNA Sequencing Indicates Upregulated BATF2 and LY6E and Downregulated ISG15 and MT2A Expression in Children with Autism Spectrum Disorder'. Together they form a unique fingerprint.

Cite this