{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:31:55Z","timestamp":1791973915045,"version":"4.4.0"},"reference-count":66,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel-United States Science Foundation","award":["2019049"],"award-info":[{"award-number":["2019049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms23179843","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T21:25:18Z","timestamp":1661894718000},"page":"9843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Blood RNA Sequencing Indicates Upregulated BATF2 and LY6E and Downregulated ISG15 and MT2A Expression in Children with Autism Spectrum Disorder"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7782-3185","authenticated-orcid":false,"given":"Irena","family":"Voinsky","sequence":"first","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-0036","authenticated-orcid":false,"given":"Yazeed","family":"Zoabi","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9913-6124","authenticated-orcid":false,"given":"Noam","family":"Shomron","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moria","family":"Harel","sequence":"additional","affiliation":[{"name":"Shaare Zedek Medical Center, Jerusalem 91031, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanoch","family":"Cassuto","sequence":"additional","affiliation":[{"name":"Shaare Zedek Medical Center, Jerusalem 91031, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-0093","authenticated-orcid":false,"given":"Joseph","family":"Tam","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-4367","authenticated-orcid":false,"given":"Shannon","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children\u2019s Research Institute, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-1895","authenticated-orcid":false,"given":"Adrienne C.","family":"Scheck","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Karim","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-2937","authenticated-orcid":false,"given":"Richard E.","family":"Frye","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, Phoenix Children\u2019s Hospital, Phoenix, AZ 85016, USA"},{"name":"Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA"},{"name":"Rossignol Medical Center, Phoenix, AZ 85050, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-4689","authenticated-orcid":false,"given":"Adi","family":"Aran","sequence":"additional","affiliation":[{"name":"Shaare Zedek Medical Center, Jerusalem 91031, Israel"},{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-1869","authenticated-orcid":false,"given":"David","family":"Gurwitz","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41576-020-0231-2","article-title":"A framework for an evidence-based gene list relevant to autism spectrum disorder","volume":"21","author":"Schaaf","year":"2020","journal-title":"Nat. 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