{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:48:22Z","timestamp":1791575302601,"version":"4.3.4"},"reference-count":118,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"28","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,7,12]]},"abstract":"<jats:p>\n            Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene (\n            <jats:italic>Ube3a<\/jats:italic>\n            ) affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of\n            <jats:italic>Ube3a<\/jats:italic>\n            via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases. Here, we test the hypothesis that increased dosage of\n            <jats:italic>Ube3a<\/jats:italic>\n            may influence autism-relevant phenotypes in a sex-biased manner. We show that mice with extra copies of Ube3a exhibit sex-biasing effects on brain connectomics and autism-relevant behaviors. These effects are associated with transcriptional dysregulation of autism-associated genes, as well as genes differentially expressed in 15q duplication and in autistic people. Increased Ube3a dosage also affects expression of genes on the X chromosome, genes influenced by sex steroid hormone, and genes sex-differentially regulated by transcription factors. These results suggest that\n            <jats:italic>Ube3a<\/jats:italic>\n            overdosage can contribute to sex bias in neurodevelopmental conditions via influence on sex-differential mechanisms.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adg1421","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T17:59:05Z","timestamp":1720807145000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Sex-biasing influence of autism-associated\n            <i>Ube3a<\/i>\n            gene overdosage at connectomic, behavioral, and transcriptomic levels"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3150-0302","authenticated-orcid":true,"given":"Caterina","family":"Montani","sequence":"first","affiliation":[{"name":"Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems, CNCS@UNITN, Rovereto, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-8505","authenticated-orcid":true,"given":"Luigi","family":"Balasco","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-6931","authenticated-orcid":true,"given":"Marco","family":"Pagani","sequence":"additional","affiliation":[{"name":"Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems, CNCS@UNITN, Rovereto, Italy."},{"name":"Autism Center, Child Mind Institute, New York, NY, USA."},{"name":"IMT School for Advanced Studies, Lucca, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5669-4369","authenticated-orcid":true,"given":"Filomena Grazia","family":"Alvino","sequence":"additional","affiliation":[{"name":"Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems, CNCS@UNITN, Rovereto, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6399-436X","authenticated-orcid":true,"given":"Noemi","family":"Barsotti","sequence":"additional","affiliation":[{"name":"Unit of Cell and Developmental Biology, Department of Biology, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6675-4014","authenticated-orcid":true,"given":"A. 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