[{"issue":"1","related_material":{"record":[{"relation":"dissertation_contains","id":"12364","status":"public"}]},"volume":39,"ec_funded":1,"publication_identifier":{"issn":["2211-1247"]},"publication_status":"published","file":[{"success":1,"file_id":"11164","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2022_CellReports_Villa.pdf","date_created":"2022-04-15T09:06:25Z","file_size":"7808644","date_updated":"2022-04-15T09:06:25Z","creator":"dernst"}],"language":[{"iso":"eng"}],"month":"04","intvolume":" 39","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"abstract":[{"lang":"eng","text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling."}],"pmid":1,"oa_version":"Published Version","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"file_date_updated":"2022-04-15T09:06:25Z","date_updated":"2024-03-27T23:30:44Z","ddc":["570"],"type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","keyword":["General Biochemistry","Genetics and Molecular Biology"],"_id":"11160","date_published":"2022-04-05T00:00:00Z","doi":"10.1016/j.celrep.2022.110615","date_created":"2022-04-15T09:03:10Z","has_accepted_license":"1","isi":1,"year":"2022","day":"05","publication":"Cell Reports","quality_controlled":"1","publisher":"Elsevier","oa":1,"acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","author":[{"full_name":"Villa, Carlo Emanuele","last_name":"Villa","first_name":"Carlo Emanuele"},{"first_name":"Cristina","full_name":"Cheroni, Cristina","last_name":"Cheroni"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter"},{"last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro","first_name":"Alejandro"},{"full_name":"Oliveira, Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara"},{"full_name":"Sacco, Roberto","last_name":"Sacco","first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Yahya","full_name":"Yahya, Aysan Çerağ","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","full_name":"Morandell, Jasmin"},{"first_name":"Michele","last_name":"Gabriele","full_name":"Gabriele, Michele"},{"first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli","orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"full_name":"Gabitto, Mariano","last_name":"Gabitto","first_name":"Mariano"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"},{"first_name":"Giuseppe","last_name":"Testa","full_name":"Testa, Giuseppe"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"article_processing_charge":"Yes","external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","citation":{"mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol. 39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","ieee":"C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” Cell Reports, vol. 39, no. 1. Elsevier, 2022.","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 2022;39(1). doi:10.1016/j.celrep.2022.110615","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","grant_number":"I04205"}],"article_number":"110615"},{"_id":"12364","type":"dissertation","status":"public","supervisor":[{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"date_updated":"2023-11-16T13:10:22Z","ddc":["570"],"department":[{"_id":"GradSch"},{"_id":"GaNo"}],"file_date_updated":"2023-09-20T22:30:03Z","abstract":[{"text":"Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders character\u0002ized by behavioral symptoms such as problems in social communication and interaction, as\r\nwell as repetitive, restricted behaviors and interests. These disorders show a high degree\r\nof heritability and hundreds of risk genes have been identifed using high throughput\r\nsequencing technologies. This genetic heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD but at the same time given rise to the concept of convergent\r\nmechanisms. Previous studies have identifed that risk genes for ASD broadly converge\r\nonto specifc functional categories with transcriptional regulation being one of the biggest\r\ngroups. In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe link the regulatory function of Setd5 to its interaction with the Paf1 and the NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing. While the former\r\nwere generated earlier in CHD8+/- organoids, the generation of the latter was shifted to\r\nlater times in favor of a prolonged progenitor expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B, KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral ganglionic eminence. As this project is still ongoing at the time of writing, future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying this shift with\r\nthe aim of linking these three ASD risk genes through biological convergence.","lang":"eng"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"09","publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","embargo":"2023-09-19","file_id":"12365","checksum":"896f4cac9adb6d3f26a6605772f4e1a3","creator":"cchlebak","file_size":20457465,"date_updated":"2023-09-20T22:30:03Z","file_name":"220923_Thesis_CDotter_Final.pdf","date_created":"2023-01-24T13:15:45Z"},{"date_created":"2023-02-02T09:15:35Z","file_name":"latex_source_CDotter_Thesis_2022.zip","date_updated":"2023-09-20T22:30:03Z","file_size":22433512,"creator":"cchlebak","file_id":"12482","checksum":"ad01bb20da163be6893b7af832e58419","content_type":"application/x-zip-compressed","embargo_to":"open_access","access_level":"closed","relation":"source_file"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"3","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"11160"}]},"ec_funded":1,"project":[{"_id":"254BA948-B435-11E9-9278-68D0E5697425","grant_number":"401299","name":"Probing development and reversibility of autism spectrum disorders"},{"_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964","name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers"},{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"citation":{"chicago":"Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12094.","ista":"Dotter C. 2022. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria.","mla":"Dotter, Christoph. Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12094.","ama":"Dotter C. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094","apa":"Dotter, C. (2022). Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12094","short":"C. Dotter, Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.","ieee":"C. Dotter, “Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","author":[{"last_name":"Dotter","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"}],"article_processing_charge":"No","title":"Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder","publisher":"Institute of Science and Technology Austria","oa":1,"has_accepted_license":"1","year":"2022","day":"19","page":"152","date_published":"2022-09-19T00:00:00Z","doi":"10.15479/at:ista:12094","date_created":"2023-01-24T13:09:57Z"},{"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","publisher":"Springer Nature","quality_controlled":"1","oa":1,"has_accepted_license":"1","isi":1,"year":"2021","day":"24","publication":"Nature Communications","date_published":"2021-05-24T00:00:00Z","doi":"10.1038/s41467-021-23123-x","date_created":"2021-05-28T11:49:46Z","article_number":"3058","project":[{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"F07807","name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"}],"citation":{"mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"last_name":"Schwarz","full_name":"Schwarz, Lena A","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Basilico","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Tasciyan","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161","full_name":"Dimchev, Georgi A","last_name":"Dimchev"},{"first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Dobler, Zoe","last_name":"Dobler","first_name":"Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","last_name":"Schur","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078"},{"orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"article_processing_charge":"No","external_id":{"isi":["000658769900010"]},"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","acknowledged_ssus":[{"_id":"PreCl"}],"abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.","lang":"eng"}],"oa_version":"Published Version","month":"05","intvolume":" 12","publication_identifier":{"eissn":["2041-1723"]},"publication_status":"published","file":[{"file_size":9358599,"date_updated":"2021-05-28T12:39:43Z","creator":"kschuh","file_name":"2021_NatureCommunications_Morandell.pdf","date_created":"2021-05-28T12:39:43Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"file_id":"9430","checksum":"337e0f7959c35ec959984cacdcb472ba"}],"language":[{"iso":"eng"}],"volume":12,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}],"record":[{"relation":"earlier_version","status":"public","id":"7800"},{"relation":"dissertation_contains","status":"public","id":"12401"}]},"issue":"1","ec_funded":1,"_id":"9429","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","keyword":["General Biochemistry","Genetics and Molecular Biology"],"date_updated":"2024-03-27T23:30:23Z","ddc":["572"],"department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"file_date_updated":"2021-05-28T12:39:43Z"},{"oa":1,"publisher":"Institute of Science and Technology Austria","month":"01","abstract":[{"text":"This dataset contains the supplementary data for the research paper \"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition\".\r\n\r\nThe contained files have the following content:\r\n'Supplementary Figures.pdf'\r\n\tAdditional figures (as referenced in the paper).\r\n'Supplementary Table 1. Statistics.xlsx'\r\n\tDetails on statistical tests performed in the paper.\r\n'Supplementary Table 2. Differentially expressed gene analysis.xlsx'\r\n\tResults for the differential gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro (ESCs, EBs, NPCs; analysis with DESeq2) samples.\r\n'Supplementary Table 3. Gene Ontology (GO) term enrichment analysis.xlsx'\r\n\tResults for the GO term enrichment analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro (GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro samples were split into upregulated and downregulated genes (up/down) and the analysis was performed on each subset (e.g. GO ESC up / GO ESC down).\r\n'Supplementary Table 4. Differentially expressed gene analysis for CFC samples.xlsx'\r\n\tResults for the differential gene expression analysis for samples from adult mice before (HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively). Each sheet shows the results for a different comparison. Sheets 1-3 show results for comparisons between timepoints for wild type (WT) samples only and sheets 4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results for comparisons between genotypes at each time point and sheet 10 contains the results for the analysis of differential expression trajectories between wild type and mutant.\r\n'Supplementary Table 5. Cluster identification.xlsx'\r\n\tResults for k-means clustering of genes by expression. Sheet 1 shows clustering of just the genes with significantly different expression trajectories between genotypes. Sheet 2 shows clustering of all genes that are significantly differentially expressed in any of the comparisons (includes also genes with same trajectories).\r\n'Supplementary Table 6. GO term cluster analysis.xlsx'\r\n\tResults for the GO term enrichment analysis and EWCE analysis for enrichment of cell type specific genes for each cluster identified by clustering genes with different expression trajectories (see Table S5, sheet 1).\r\n'Supplementary Table 7. Setd5 mass spectrometry results.xlsx'\r\n\tResults showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet 1 shows protein protein interaction data generated from these results (combined with data from the STRING database. Sheet 2 shows the results of the statistical analysis with limma.\r\n'Supplementary Table 8. PolII ChIP-seq analysis.xlsx'\r\n\tResults for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows results for differential binding of PolII at the transcription start site (TSS) between genotypes and sheets 2+3 show the corresponding GO enrichment analysis for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with increased binding of PolII at the TSS.","lang":"eng"}],"oa_version":"Published Version","date_created":"2019-03-07T13:32:35Z","date_published":"2019-01-09T00:00:00Z","related_material":{"record":[{"relation":"research_paper","status":"public","id":"3"}]},"doi":"10.15479/AT:ISTA:6074","year":"2019","has_accepted_license":"1","day":"09","file":[{"creator":"dernst","date_updated":"2020-07-14T12:47:18Z","file_size":33202743,"date_created":"2019-03-07T13:37:19Z","file_name":"Setd5_paper.zip","access_level":"open_access","relation":"supplementary_material","content_type":"application/zip","checksum":"bc1b285edca9e98a2c63d153c79bb75b","file_id":"6084"}],"type":"research_data","status":"public","_id":"6074","article_processing_charge":"No","author":[{"orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"title":"Supplementary data for the research paper \"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition\"","file_date_updated":"2020-07-14T12:47:18Z","department":[{"_id":"GaNo"}],"date_updated":"2024-02-21T13:41:01Z","citation":{"ista":"Dotter C, Novarino G. 2019. Supplementary data for the research paper ‘Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:6074.","chicago":"Dotter, Christoph, and Gaia Novarino. “Supplementary Data for the Research Paper ‘Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.’” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6074.","short":"C. Dotter, G. Novarino, (2019).","ieee":"C. Dotter and G. Novarino, “Supplementary data for the research paper ‘Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.’” Institute of Science and Technology Austria, 2019.","apa":"Dotter, C., & Novarino, G. (2019). Supplementary data for the research paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6074","ama":"Dotter C, Novarino G. Supplementary data for the research paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.” 2019. doi:10.15479/AT:ISTA:6074","mla":"Dotter, Christoph, and Gaia Novarino. Supplementary Data for the Research Paper “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6074."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"]},{"project":[{"name":"Probing development and reversibility of autism spectrum disorders","grant_number":"401299","_id":"254BA948-B435-11E9-9278-68D0E5697425"}],"citation":{"short":"E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727.","ieee":"E. Deliu et al., “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.","ama":"Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2","apa":"Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2","mla":"Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2.","ista":"Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727.","chicago":"Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"first_name":"Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293","last_name":"Deliu"},{"full_name":"Arecco, Niccoló","last_name":"Arecco","first_name":"Niccoló"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter"},{"first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","last_name":"Contreras"},{"full_name":"Girardot, Charles","last_name":"Girardot","first_name":"Charles"},{"first_name":"Eva","last_name":"Käsper","full_name":"Käsper, Eva"},{"full_name":"Kozlova, Alena","last_name":"Kozlova","first_name":"Alena","id":"C50A9596-02D0-11E9-976E-E38CFE5CBC1D"},{"id":"3065DFC4-F248-11E8-B48F-1D18A9856A87","first_name":"Kasumi","last_name":"Kishi","full_name":"Kishi, Kasumi"},{"id":"B6467F20-02D0-11E9-BDA5-E960C241894A","first_name":"Ilaria","last_name":"Chiaradia","orcid":"0000-0002-9529-4464","full_name":"Chiaradia, Ilaria"},{"full_name":"Noh, Kyung","last_name":"Noh","first_name":"Kyung"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"publist_id":"8054","external_id":{"isi":["000451324700010"]},"article_processing_charge":"No","title":"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition","acknowledgement":"This work was supported by the Simons Foundation Autism Research Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.","quality_controlled":"1","publisher":"Nature Publishing Group","oa":1,"has_accepted_license":"1","isi":1,"year":"2018","day":"19","publication":"Nature Neuroscience","page":"1717 - 1727","date_published":"2018-11-19T00:00:00Z","doi":"10.1038/s41593-018-0266-2","date_created":"2018-12-11T11:44:05Z","_id":"3","type":"journal_article","article_type":"original","status":"public","pubrep_id":"1071","date_updated":"2024-03-27T23:30:44Z","ddc":["570"],"file_date_updated":"2020-07-14T12:45:58Z","department":[{"_id":"GaNo"},{"_id":"EdHa"}],"abstract":[{"text":"SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder.","lang":"eng"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"oa_version":"Submitted Version","scopus_import":"1","month":"11","intvolume":" 21","publication_status":"published","file":[{"creator":"dernst","file_size":8167169,"date_updated":"2020-07-14T12:45:58Z","file_name":"2017_NatureNeuroscience_Deliu.pdf","date_created":"2019-04-09T07:41:57Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"6255","checksum":"60abd0f05b7cdc08a6b0ec460884084f"}],"language":[{"iso":"eng"}],"related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/","description":"News on IST Homepage"}],"record":[{"relation":"popular_science","id":"6074","status":"public"},{"status":"public","id":"12364","relation":"dissertation_contains"}]},"issue":"12","volume":21},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"885","status":"public","_id":"713","department":[{"_id":"GaNo"},{"_id":"SiHi"}],"file_date_updated":"2020-07-14T12:47:50Z","date_updated":"2021-01-12T08:11:57Z","ddc":["576"],"scopus_import":1,"intvolume":" 6","month":"08","abstract":[{"lang":"eng","text":"To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta."}],"oa_version":"Published Version","volume":6,"publication_status":"published","publication_identifier":{"issn":["2050084X"]},"language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"5020","checksum":"1ace3462e64a971b9ead896091829549","creator":"system","date_updated":"2020-07-14T12:47:50Z","file_size":6399510,"date_created":"2018-12-12T10:13:36Z","file_name":"IST-2017-885-v1+1_elife-25125-figures-v2.pdf"},{"creator":"system","file_size":4264398,"date_updated":"2020-07-14T12:47:50Z","file_name":"IST-2017-885-v1+2_elife-25125-v2.pdf","date_created":"2018-12-12T10:13:36Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"5021","checksum":"6241dc31eeb87b03facadec3a53a6827"}],"project":[{"call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions"}],"article_number":"e25125","publist_id":"6971","author":[{"first_name":"Daniel","full_name":"Andergassen, Daniel","last_name":"Andergassen"},{"full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Wenzel, Dyniel","last_name":"Wenzel","first_name":"Dyniel"},{"first_name":"Verena","last_name":"Sigl","full_name":"Sigl, Verena"},{"full_name":"Bammer, Philipp","last_name":"Bammer","first_name":"Philipp"},{"first_name":"Markus","full_name":"Muckenhuber, Markus","last_name":"Muckenhuber"},{"first_name":"Daniela","last_name":"Mayer","full_name":"Mayer, Daniela"},{"first_name":"Tomasz","last_name":"Kulinski","full_name":"Kulinski, Tomasz"},{"first_name":"Hans","last_name":"Theussl","full_name":"Theussl, Hans"},{"first_name":"Josef","last_name":"Penninger","full_name":"Penninger, Josef"},{"first_name":"Christoph","last_name":"Bock","full_name":"Bock, Christoph"},{"first_name":"Denise","last_name":"Barlow","full_name":"Barlow, Denise"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian"},{"first_name":"Quanah","last_name":"Hudson","full_name":"Hudson, Quanah"}],"title":"Mapping the mouse Allelome reveals tissue specific regulation of allelic expression","citation":{"ista":"Andergassen D, Dotter C, Wenzel D, Sigl V, Bammer P, Muckenhuber M, Mayer D, Kulinski T, Theussl H, Penninger J, Bock C, Barlow D, Pauler F, Hudson Q. 2017. Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. eLife. 6, e25125.","chicago":"Andergassen, Daniel, Christoph Dotter, Dyniel Wenzel, Verena Sigl, Philipp Bammer, Markus Muckenhuber, Daniela Mayer, et al. “Mapping the Mouse Allelome Reveals Tissue Specific Regulation of Allelic Expression.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25125.","ieee":"D. Andergassen et al., “Mapping the mouse Allelome reveals tissue specific regulation of allelic expression,” eLife, vol. 6. eLife Sciences Publications, 2017.","short":"D. Andergassen, C. Dotter, D. Wenzel, V. Sigl, P. Bammer, M. Muckenhuber, D. Mayer, T. Kulinski, H. Theussl, J. Penninger, C. Bock, D. Barlow, F. Pauler, Q. Hudson, ELife 6 (2017).","apa":"Andergassen, D., Dotter, C., Wenzel, D., Sigl, V., Bammer, P., Muckenhuber, M., … Hudson, Q. (2017). Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25125","ama":"Andergassen D, Dotter C, Wenzel D, et al. Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. eLife. 2017;6. doi:10.7554/eLife.25125","mla":"Andergassen, Daniel, et al. “Mapping the Mouse Allelome Reveals Tissue Specific Regulation of Allelic Expression.” ELife, vol. 6, e25125, eLife Sciences Publications, 2017, doi:10.7554/eLife.25125."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"publisher":"eLife Sciences Publications","quality_controlled":"1","date_created":"2018-12-11T11:48:05Z","date_published":"2017-08-14T00:00:00Z","doi":"10.7554/eLife.25125","year":"2017","has_accepted_license":"1","publication":"eLife","day":"14"},{"ddc":["576"],"date_updated":"2021-01-12T06:49:20Z","file_date_updated":"2020-07-14T12:44:41Z","department":[{"_id":"GaNo"}],"_id":"1240","pubrep_id":"709","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","language":[{"iso":"eng"}],"file":[{"date_created":"2018-12-12T10:10:05Z","file_name":"IST-2016-709-v1+1_s13059-016-0873-8.pdf","date_updated":"2020-07-14T12:44:41Z","file_size":2914601,"creator":"system","file_id":"4789","checksum":"a268beee1a690801c83ec6729f9ebc5b","content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"publication_status":"published","volume":17,"issue":"1","oa_version":"Published Version","abstract":[{"text":"Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at 1- or more than 1-month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in two independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers.","lang":"eng"}],"intvolume":" 17","month":"01","scopus_import":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Kornienko, Aleksandra, Christoph Dotter, Philipp Guenzl, Heinz Gisslinger, Bettina Gisslinger, Ciara Cleary, Robert Kralovics, Florian Pauler, and Denise Barlow. “Long Non-Coding RNAs Display Higher Natural Expression Variation than Protein-Coding Genes in Healthy Humans.” Genome Biology. BioMed Central, 2016. https://doi.org/10.1186/s13059-016-0873-8.","ista":"Kornienko A, Dotter C, Guenzl P, Gisslinger H, Gisslinger B, Cleary C, Kralovics R, Pauler F, Barlow D. 2016. Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. 17(1), 14.","mla":"Kornienko, Aleksandra, et al. “Long Non-Coding RNAs Display Higher Natural Expression Variation than Protein-Coding Genes in Healthy Humans.” Genome Biology, vol. 17, no. 1, 14, BioMed Central, 2016, doi:10.1186/s13059-016-0873-8.","apa":"Kornienko, A., Dotter, C., Guenzl, P., Gisslinger, H., Gisslinger, B., Cleary, C., … Barlow, D. (2016). Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. BioMed Central. https://doi.org/10.1186/s13059-016-0873-8","ama":"Kornienko A, Dotter C, Guenzl P, et al. Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. 2016;17(1). doi:10.1186/s13059-016-0873-8","short":"A. Kornienko, C. Dotter, P. Guenzl, H. Gisslinger, B. Gisslinger, C. Cleary, R. Kralovics, F. Pauler, D. Barlow, Genome Biology 17 (2016).","ieee":"A. Kornienko et al., “Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans,” Genome Biology, vol. 17, no. 1. BioMed Central, 2016."},"title":"Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans","publist_id":"6093","author":[{"first_name":"Aleksandra","full_name":"Kornienko, Aleksandra","last_name":"Kornienko"},{"full_name":"Dotter, Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"},{"first_name":"Philipp","full_name":"Guenzl, Philipp","last_name":"Guenzl"},{"last_name":"Gisslinger","full_name":"Gisslinger, Heinz","first_name":"Heinz"},{"last_name":"Gisslinger","full_name":"Gisslinger, Bettina","first_name":"Bettina"},{"full_name":"Cleary, Ciara","last_name":"Cleary","first_name":"Ciara"},{"first_name":"Robert","last_name":"Kralovics","full_name":"Kralovics, Robert"},{"full_name":"Pauler, Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian"},{"first_name":"Denise","full_name":"Barlow, Denise","last_name":"Barlow"}],"article_number":"14","publication":"Genome Biology","day":"29","year":"2016","has_accepted_license":"1","date_created":"2018-12-11T11:50:53Z","doi":"10.1186/s13059-016-0873-8","date_published":"2016-01-29T00:00:00Z","acknowledgement":"This study was partly funded by the Austrian Science Fund (FWF F43-B09, FWF W1207-B09). PMG is a recipient of a DOC Fellowship of the Austrian Academy of Sciences.\r\nWe thank Ruth Klement, Tomasz Kulinski, Elisangela Valente, Elisabeth Salzer,\r\nand Roland Jäger for technical/bioinformatic assistance and advice, the CeMM\r\nIT department and José Manuel Molero for help and advice on software usage,\r\nthe Biomedical Sequencing Facility (http://biomedical-sequencing.at/) for\r\nsequencing and advice, Jacques Colinge, Daniel Andergassen, and Tomasz\r\nKulinski for discussions, Quanah Hudson and Jörg Menche for reading and\r\ncommenting on the manuscript.","oa":1,"publisher":"BioMed Central","quality_controlled":"1"},{"page":"1481 - 1494","date_published":"2016-12-01T00:00:00Z","doi":"10.1016/j.cell.2016.11.013","date_created":"2018-12-11T11:50:35Z","has_accepted_license":"1","year":"2016","day":"01","publication":"Cell","quality_controlled":"1","publisher":"Cell Press","oa":1,"acknowledgement":"This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu, and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900 to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.), the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility","author":[{"last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara","first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","last_name":"Deliu","full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293"},{"last_name":"Dotter","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"},{"last_name":"Kara","full_name":"Kara, Majdi","first_name":"Majdi"},{"first_name":"Philipp","last_name":"Janiesch","full_name":"Janiesch, Philipp"},{"full_name":"Scalise, Mariafrancesca","last_name":"Scalise","first_name":"Mariafrancesca"},{"first_name":"Michele","full_name":"Galluccio, Michele","last_name":"Galluccio"},{"first_name":"Mateja","full_name":"Tesulov, Mateja","last_name":"Tesulov"},{"id":"3F4D1282-F248-11E8-B48F-1D18A9856A87","first_name":"Emanuela","last_name":"Morelli","full_name":"Morelli, Emanuela"},{"last_name":"Sönmez","full_name":"Sönmez, Fatma","first_name":"Fatma"},{"first_name":"Kaya","full_name":"Bilgüvar, Kaya","last_name":"Bilgüvar"},{"first_name":"Ryuichi","full_name":"Ohgaki, Ryuichi","last_name":"Ohgaki"},{"first_name":"Yoshikatsu","full_name":"Kanai, Yoshikatsu","last_name":"Kanai"},{"full_name":"Johansen, Anide","last_name":"Johansen","first_name":"Anide"},{"first_name":"Seham","full_name":"Esharif, Seham","last_name":"Esharif"},{"first_name":"Tawfeg","last_name":"Ben Omran","full_name":"Ben Omran, Tawfeg"},{"first_name":"Meral","full_name":"Topcu, Meral","last_name":"Topcu"},{"first_name":"Avner","full_name":"Schlessinger, Avner","last_name":"Schlessinger"},{"first_name":"Cesare","full_name":"Indiveri, Cesare","last_name":"Indiveri"},{"last_name":"Duncan","full_name":"Duncan, Kent","first_name":"Kent"},{"first_name":"Ahmet","last_name":"Caglayan","full_name":"Caglayan, Ahmet"},{"last_name":"Günel","full_name":"Günel, Murat","first_name":"Murat"},{"last_name":"Gleeson","full_name":"Gleeson, Joseph","first_name":"Joseph"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"publist_id":"6170","article_processing_charge":"No","title":"Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder","citation":{"mla":"Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167, no. 6, Cell Press, 2016, pp. 1481–94, doi:10.1016/j.cell.2016.11.013.","apa":"Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.013","ama":"Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494. doi:10.1016/j.cell.2016.11.013","ieee":"D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167, no. 6. Cell Press, pp. 1481–1494, 2016.","short":"D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise, M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai, A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri, K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494.","chicago":"Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.013.","ista":"Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"name":"Transmembrane Transporters in Health and Disease","grant_number":"F03523","call_identifier":"FWF","_id":"25473368-B435-11E9-9278-68D0E5697425"}],"volume":167,"related_material":{"record":[{"id":"395","status":"public","relation":"dissertation_contains"}]},"issue":"6","publication_status":"published","file":[{"file_name":"IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf","date_created":"2018-12-12T10:13:44Z","file_size":73907957,"date_updated":"2020-07-14T12:44:37Z","creator":"system","file_id":"5030","checksum":"7fe01ab12a6610d3db421e0136db2f77","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"scopus_import":"1","month":"12","intvolume":" 167","abstract":[{"lang":"eng","text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function."}],"oa_version":"Submitted Version","file_date_updated":"2020-07-14T12:44:37Z","department":[{"_id":"GaNo"}],"date_updated":"2024-03-27T23:30:12Z","ddc":["576","616"],"article_type":"original","type":"journal_article","status":"public","pubrep_id":"771","_id":"1183"},{"month":"07","intvolume":" 43","scopus_import":1,"oa_version":"Published Version","abstract":[{"text":"Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.","lang":"eng"}],"volume":43,"issue":"21","file":[{"creator":"dernst","date_updated":"2020-07-14T12:44:58Z","file_size":6863297,"date_created":"2018-12-20T14:18:57Z","file_name":"2015_NucleicAcidsRes_Andergassen.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"385b83854fd0eb2e4f386867da2823e2","file_id":"5768"}],"language":[{"iso":"eng"}],"publication_status":"published","status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"1497","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:44:58Z","ddc":["570"],"date_updated":"2021-01-12T06:51:09Z","quality_controlled":"1","publisher":"Oxford University Press","oa":1,"acknowledgement":"Austrian Science Fund [FWF P25185-B22, FWF F4302- B09, FWFW1207-B09]. Funding for open access charge: Austrian Science Fund.\r\nWe thank Florian Breitwieser for advice during the early stages of this project. High-throughput sequencing was conducted by the Biomedical Sequencing Facility (BSF) at CeMM in Vienna.","date_published":"2015-07-21T00:00:00Z","doi":"10.1093/nar/gkv727","date_created":"2018-12-11T11:52:22Z","day":"21","publication":"Nucleic Acids Research","has_accepted_license":"1","year":"2015","article_number":"e146","title":"Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data","publist_id":"5682","author":[{"first_name":"Daniel","last_name":"Andergassen","full_name":"Andergassen, Daniel"},{"last_name":"Dotter","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"},{"first_name":"Tomasz","last_name":"Kulinski","full_name":"Kulinski, Tomasz"},{"first_name":"Philipp","full_name":"Guenzl, Philipp","last_name":"Guenzl"},{"first_name":"Philipp","last_name":"Bammer","full_name":"Bammer, Philipp"},{"first_name":"Denise","full_name":"Barlow, Denise","last_name":"Barlow"},{"first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian"},{"first_name":"Quanah","full_name":"Hudson, Quanah","last_name":"Hudson"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Andergassen D, Dotter C, Kulinski T, Guenzl P, Bammer P, Barlow D, Pauler F, Hudson Q. 2015. Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. 43(21), e146.","chicago":"Andergassen, Daniel, Christoph Dotter, Tomasz Kulinski, Philipp Guenzl, Philipp Bammer, Denise Barlow, Florian Pauler, and Quanah Hudson. “Allelome.PRO, a Pipeline to Define Allele-Specific Genomic Features from High-Throughput Sequencing Data.” Nucleic Acids Research. Oxford University Press, 2015. https://doi.org/10.1093/nar/gkv727.","ieee":"D. Andergassen et al., “Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data,” Nucleic Acids Research, vol. 43, no. 21. Oxford University Press, 2015.","short":"D. Andergassen, C. Dotter, T. Kulinski, P. Guenzl, P. Bammer, D. Barlow, F. Pauler, Q. Hudson, Nucleic Acids Research 43 (2015).","apa":"Andergassen, D., Dotter, C., Kulinski, T., Guenzl, P., Bammer, P., Barlow, D., … Hudson, Q. (2015). Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. Oxford University Press. https://doi.org/10.1093/nar/gkv727","ama":"Andergassen D, Dotter C, Kulinski T, et al. Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. 2015;43(21). doi:10.1093/nar/gkv727","mla":"Andergassen, Daniel, et al. “Allelome.PRO, a Pipeline to Define Allele-Specific Genomic Features from High-Throughput Sequencing Data.” Nucleic Acids Research, vol. 43, no. 21, e146, Oxford University Press, 2015, doi:10.1093/nar/gkv727."}}]