{"entity": "researcher", "timestamp": "2026-07-13T09:09:40.275Z", "family": "Eichler", "given": "Evan E", "initials": "EE", "orcid": "0000-0002-8246-4014", "affiliations": ["Department of Genome Sciences, University of Washington, Seattle, WA, USA. eee@gs.washington.edu.", "Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA. eee@gs.washington.edu."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/43901cc9fc3b4f5c9a18260e36558eb9.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/43901cc9fc3b4f5c9a18260e36558eb9"}}, "publications": [{"entity": "publication", "iuid": "49731da5fcb34c8ea7886628fc04fb77", "links": {"self": {"href": "https://publications.scilifelab.se/publication/49731da5fcb34c8ea7886628fc04fb77.json"}, "display": {"href": "https://publications.scilifelab.se/publication/49731da5fcb34c8ea7886628fc04fb77"}}, "title": "LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification.", "authors": [{"family": "Garza", "given": "Raquel", "initials": "R", "orcid": "0000-0002-2524-3055", "researcher": {"href": "https://publications.scilifelab.se/researcher/67d53399af304283ba62e0646acdc612.json"}}, {"family": "Atacho", "given": "Diahann A M", "initials": "DAM", "orcid": "0000-0002-6158-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2c36afdcd3147f39ad6e34623dbec6c.json"}}, {"family": "Adami", "given": "Anita", "initials": "A", "orcid": "0000-0002-9421-7942", "researcher": {"href": "https://publications.scilifelab.se/researcher/174398a7905b490ba8a41108d65bfe1d.json"}}, {"family": "Gerdes", "given": "Patricia", "initials": "P", "orcid": "0000-0002-1148-9134", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8571bfad113498c8fdb09fb74d7b2bd.json"}}, {"family": "Vinod", "given": "Meghna", "initials": "M", "orcid": "0009-0008-9057-6834", "researcher": {"href": "https://publications.scilifelab.se/researcher/de9ee947419d440f82ea756abb28d7f9.json"}}, {"family": "Hsieh", "given": "PingHsun", "initials": "P", "orcid": "0000-0001-8294-6227", "researcher": {"href": "https://publications.scilifelab.se/researcher/00e1f1a68324444ea4e89ec62fc12d64.json"}}, {"family": "Karlsson", "given": "Ofelia", "initials": "O"}, {"family": "Horvath", "given": "Vivien", "initials": "V", "orcid": "0000-0001-6536-1710", "researcher": {"href": "https://publications.scilifelab.se/researcher/7be63bec9f4a4bf2a0fa907973cef28d.json"}}, {"family": "Johansson", "given": "Pia A", "initials": "PA", "orcid": "0000-0002-6938-4060", "researcher": {"href": "https://publications.scilifelab.se/researcher/28206ae896f34a2c85c2ed863d4eb53e.json"}}, {"family": "Pandiloski", "given": "Ninoslav", "initials": "N", "orcid": "0000-0002-1204-5359", "researcher": {"href": "https://publications.scilifelab.se/researcher/156ba4836c234d739d10e0da00acce9b.json"}}, {"family": "Matas-Fuentes", "given": "Jon", "initials": "J", "orcid": "0009-0000-9253-1172", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a4d7313057548238c742aefc9c07ca8.json"}}, {"family": "Quaegebeur", "given": "Annelies", "initials": "A", "orcid": "0000-0001-5357-9341", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2f37a3920374d37a1d5508b580ddac2.json"}}, {"family": "Kouli", "given": "Antonina", "initials": "A", "orcid": "0000-0001-6553-6154", "researcher": {"href": "https://publications.scilifelab.se/researcher/6894568633154da5aad7f93413297f43.json"}}, {"family": "Sharma", "given": "Yogita", "initials": "Y"}, {"family": "J\u00f6nsson", "given": "Marie E", "initials": "ME", "orcid": "0000-0002-1184-6269", "researcher": {"href": "https://publications.scilifelab.se/researcher/73ddc70ea52e4bfc82f97a3fc35c09cd.json"}}, {"family": "Monni", "given": "Emanuela", "initials": "E", "orcid": "0000-0003-0083-1050", "researcher": {"href": "https://publications.scilifelab.se/researcher/3becd99e5a7d4d5e8a4d893045dcb590.json"}}, {"family": "Englund", "given": "Elisabet", "initials": "E", "orcid": "0000-0002-2708-2443", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c98fa2b2e7e4e318cd00eb1e8e3ac7a.json"}}, {"family": "Eichler", "given": "Evan E", "initials": "EE", "orcid": "0000-0002-8246-4014", "researcher": {"href": "https://publications.scilifelab.se/researcher/43901cc9fc3b4f5c9a18260e36558eb9.json"}}, {"family": "Gale Hammell", "given": "Molly", "initials": "M", "orcid": "0000-0003-0405-8392", "researcher": {"href": "https://publications.scilifelab.se/researcher/ecbbae421ea14d5c983755df8f519930.json"}}, {"family": "Barker", "given": "Roger A", "initials": "RA"}, {"family": "Kokaia", "given": "Zaal", "initials": "Z"}, {"family": "Douse", "given": "Christopher H", "initials": "CH", "orcid": "0000-0002-1604-8944", "researcher": {"href": "https://publications.scilifelab.se/researcher/d645238072a64ecdae736e3194b536c2.json"}}, {"family": "Jakobsson", "given": "Johan", "initials": "J", "orcid": "0000-0003-0669-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b08f33ec79b4a36a5f62223d7174201.json"}}], "type": "journal article", "published": "2023-11-03", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "9", "issue": "44", "pages": "eadh9543", "issn-l": "2375-2548"}, "abstract": "The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.", "doi": "10.1126/sciadv.adh9543", "pmid": "37910626", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "NGI Long read": "Service", "Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10619931"}], "notes": [], "created": "2023-11-02T13:41:55.614Z", "modified": "2023-11-21T18:50:22.968Z"}, {"entity": "publication", "iuid": "44584992ffd84031895bb087891f144e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44584992ffd84031895bb087891f144e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44584992ffd84031895bb087891f144e"}}, "title": "Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.", "authors": [{"family": "Gillentine", "given": "Madelyn A", "initials": "MA"}, {"family": "Wang", "given": "Tianyun", "initials": "T"}, {"family": "Hoekzema", "given": "Kendra", "initials": "K"}, {"family": "Rosenfeld", "given": "Jill", "initials": "J"}, {"family": "Liu", "given": "Pengfei", "initials": "P"}, {"family": "Guo", "given": "Hui", "initials": "H"}, {"family": "Kim", "given": "Chang N", "initials": "CN"}, {"family": "De Vries", "given": "Bert B A", "initials": "BBA"}, {"family": "Vissers", "given": "Lisenka E L M", "initials": "LELM"}, {"family": "Nordenskjold", "given": "Magnus", "initials": "M"}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Gecz", "given": "Jozef", "initials": "J"}, {"family": "Iascone", "given": "Maria", "initials": "M"}, {"family": "Cereda", "given": "Anna", "initials": "A"}, {"family": "Scatigno", "given": "Agnese", "initials": "A"}, {"family": "Maitz", "given": "Silvia", "initials": "S"}, {"family": "Zanni", "given": "Ginevra", "initials": "G"}, {"family": "Bertini", "given": "Enrico", "initials": "E"}, {"family": "Zweier", "given": "Christiane", "initials": "C"}, {"family": "Schuhmann", "given": "Sarah", "initials": "S"}, {"family": "Wiesener", "given": "Antje", "initials": "A"}, {"family": "Pepper", "given": "Micah", "initials": "M"}, {"family": "Panjwani", "given": "Heena", "initials": "H"}, {"family": "Torti", "given": "Erin", "initials": "E"}, {"family": "Abid", "given": "Farida", "initials": "F"}, {"family": "Anselm", "given": "Irina", "initials": "I"}, {"family": "Srivastava", "given": "Siddharth", "initials": "S"}, {"family": "Atwal", "given": "Paldeep", "initials": "P"}, {"family": "Bacino", "given": "Carlos A", "initials": "CA"}, {"family": "Bhat", "given": "Gifty", "initials": "G"}, {"family": "Cobian", "given": "Katherine", "initials": "K"}, {"family": "Bird", "given": "Lynne M", "initials": "LM"}, {"family": "Friedman", "given": "Jennifer", "initials": "J"}, {"family": "Wright", "given": "Meredith S", "initials": "MS"}, {"family": "Callewaert", "given": "Bert", "initials": "B"}, {"family": "Petit", "given": "Florence", "initials": "F"}, {"family": "Mathieu", "given": "Sophie", "initials": "S"}, {"family": "Afenjar", "given": "Alexandra", "initials": "A"}, {"family": "Christensen", "given": "Celenie K", "initials": "CK"}, {"family": "White", "given": "Kerry M", "initials": "KM"}, {"family": "Elpeleg", "given": "Orly", "initials": "O"}, {"family": "Berger", "given": "Itai", "initials": "I"}, {"family": "Espineli", "given": "Edward J", "initials": "EJ"}, {"family": "Fagerberg", "given": "Christina", "initials": "C"}, {"family": "Brasch-Andersen", "given": "Charlotte", "initials": "C"}, {"family": "Hansen", "given": "Lars Kj\u00e6rsgaard", "initials": "LK"}, {"family": "Feyma", "given": "Timothy", "initials": "T"}, {"family": "Hughes", "given": "Susan", "initials": "S"}, {"family": "Thiffault", "given": "Isabelle", "initials": "I"}, {"family": "Sullivan", "given": "Bonnie", "initials": "B"}, {"family": "Yan", "given": "Shuang", "initials": "S"}, {"family": "Keller", "given": "Kory", "initials": "K"}, {"family": "Keren", "given": "Boris", "initials": "B"}, {"family": "Mignot", "given": "Cyril", "initials": "C"}, {"family": "Kooy", "given": "Frank", "initials": "F"}, {"family": "Meuwissen", "given": "Marije", "initials": "M"}, {"family": "Basinger", "given": "Alice", "initials": "A"}, {"family": "Kukolich", "given": "Mary", "initials": "M"}, {"family": "Philips", "given": "Meredith", "initials": "M"}, {"family": "Ortega", "given": "Lucia", "initials": "L"}, {"family": "Drummond-Borg", "given": "Margaret", "initials": "M"}, {"family": "Lauridsen", "given": "Mathilde", "initials": "M"}, {"family": "Sorensen", "given": "Kristina", "initials": "K"}, {"family": "Lehman", "given": "Anna", "initials": "A"}, {"family": "CAUSES Study", "given": "", "initials": ""}, {"family": "Lopez-Rangel", "given": "Elena", "initials": "E"}, {"family": "Levy", "given": "Paul", "initials": "P"}, {"family": "Lessel", "given": "Davor", "initials": "D"}, {"family": "Lotze", "given": "Timothy", "initials": "T"}, {"family": "Madan-Khetarpal", "given": "Suneeta", "initials": "S"}, {"family": "Sebastian", "given": "Jessica", "initials": "J"}, {"family": "Vento", "given": "Jodie", "initials": "J"}, {"family": "Vats", "given": "Divya", "initials": "D"}, {"family": "Benman", "given": "L Manace", "initials": "LM"}, {"family": "Mckee", "given": "Shane", "initials": "S"}, {"family": "Mirzaa", "given": "Ghayda M", "initials": "GM"}, {"family": "Muss", "given": "Candace", "initials": "C"}, {"family": "Pappas", "given": "John", "initials": "J"}, {"family": "Peeters", "given": "Hilde", "initials": "H"}, {"family": "Romano", "given": "Corrado", "initials": "C"}, {"family": "Elia", "given": "Maurizio", "initials": "M"}, {"family": "Galesi", "given": "Ornella", "initials": "O"}, {"family": "Simon", "given": "Marleen E H", "initials": "MEH"}, {"family": "van Gassen", "given": "Koen L I", "initials": "KLI"}, {"family": "Simpson", "given": "Kara", "initials": "K"}, {"family": "Stratton", "given": "Robert", "initials": "R"}, {"family": "Syed", "given": "Sabeen", "initials": "S"}, {"family": "Thevenon", "given": "Julien", "initials": "J"}, {"family": "Palafoll", "given": "Irene Valenzuela", "initials": "IV"}, {"family": "Vitobello", "given": "Antonio", "initials": "A"}, {"family": "Bournez", "given": "Marie", "initials": "M"}, {"family": "Faivre", "given": "Laurence", "initials": "L"}, {"family": "Xia", "given": "Kun", "initials": "K"}, {"family": "SPARK Consortium", "given": "", "initials": ""}, {"family": "Earl", "given": "Rachel K", "initials": "RK"}, {"family": "Nowakowski", "given": "Tomasz", "initials": "T"}, {"family": "Bernier", "given": "Raphael A", "initials": "RA"}, {"family": "Eichler", "given": "Evan E", "initials": "EE", "orcid": "0000-0002-8246-4014", "researcher": {"href": "https://publications.scilifelab.se/researcher/43901cc9fc3b4f5c9a18260e36558eb9.json"}}], "type": "journal article", "published": "2021-04-19", "journal": {"title": "Genome Med", "issn": "1756-994X", "volume": "13", "issue": "1", "pages": "63", "issn-l": "1756-994X"}, "abstract": "With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations.\n\nWe tested our hypothesis by considering gene families that have multiple members with an enrichment of de novo variants among NDDs, as determined by previous meta-analyses. One of these gene families is the heterogeneous nuclear ribonucleoproteins (hnRNPs), which has 33 members, five of which have been recently identified as NDD genes (HNRNPK, HNRNPU, HNRNPH1, HNRNPH2, and HNRNPR) and two of which have significant enrichment in our previous meta-analysis of probands with NDDs (HNRNPU and SYNCRIP). Utilizing protein homology, mutation analyses, gene expression analyses, and phenotypic characterization, we provide evidence for variation in 12 HNRNP genes as candidates for NDDs. Seven are potentially novel while the remaining genes in the family likely do not significantly contribute to NDD risk.\n\nWe report 119 new NDD cases (64 de novo variants) through sequencing and international collaborations and combined with published clinical case reports. We consider 235 cases with gene-disruptive single-nucleotide variants or indels and 15 cases with small copy number variants. Three hnRNP-encoding genes reach nominal or exome-wide significance for de novo variant enrichment, while nine are candidates for pathogenic mutations. Comparison of HNRNP gene expression shows a pattern consistent with a role in cerebral cortical development with enriched expression among radial glial progenitors. Clinical assessment of probands (n = 188-221) expands the phenotypes associated with HNRNP rare variants, and phenotypes associated with variation in the HNRNP genes distinguishes them as a subgroup of NDDs.\n\nOverall, our novel approach of exploiting gene families in NDDs identifies new HNRNP-related disorders, expands the phenotypes of known HNRNP-related disorders, strongly implicates disruption of the hnRNPs as a whole in NDDs, and supports that NDD subtypes likely have shared molecular pathogenesis. To date, this is the first study to identify novel genetic disorders based on the presence of disorders in related genes. We also perform the first phenotypic analyses focusing on related genes. Finally, we show that radial glial expression of these genes is likely critical during neurodevelopment. This is important for diagnostics, as well as developing strategies to best study these genes for the development of therapeutics.", "doi": "10.1186/s13073-021-00870-6", "pmid": "33874999", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13073-021-00870-6"}, {"db": "pmc", "key": "PMC8056596"}], "notes": [], "created": "2021-11-20T12:20:16.589Z", "modified": "2021-11-20T12:20:16.626Z"}, {"entity": "publication", "iuid": "c4ca7ddb792e49aab70137c27e6970f3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c4ca7ddb792e49aab70137c27e6970f3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c4ca7ddb792e49aab70137c27e6970f3"}}, "title": "Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.", "authors": [{"family": "Wang", "given": "Tianyun", "initials": "T", "orcid": "0000-0002-5179-087X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f8343adbdf84296a4bf04c6890d49d2.json"}}, {"family": "Hoekzema", "given": "Kendra", "initials": "K"}, {"family": "Vecchio", "given": "Davide", "initials": "D", "orcid": "0000-0003-2907-3206", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7d64eefa6a041caad3a8c860e76d84e.json"}}, {"family": "Wu", "given": "Huidan", "initials": "H"}, {"family": "Sulovari", "given": "Arvis", "initials": "A", "orcid": "0000-0003-4354-9020", "researcher": {"href": "https://publications.scilifelab.se/researcher/85f6043d9c7c4ca49ced9ed1c0f97340.json"}}, {"family": "Coe", "given": "Bradley P", "initials": "BP"}, {"family": "Gillentine", "given": "Madelyn A", "initials": "MA", "orcid": "0000-0002-8989-2214", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e5086e94ffb4bc7a8367b15d17b876e.json"}}, {"family": "Wilfert", "given": "Amy B", "initials": "AB"}, {"family": "Perez-Jurado", "given": "Luis A", "initials": "LA"}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Sleyp", "given": "Yoeri", "initials": "Y"}, {"family": "Earl", "given": "Rachel K", "initials": "RK"}, {"family": "Rosenfeld", "given": "Jill A", "initials": "JA", "orcid": "0000-0001-5664-7987", "researcher": {"href": "https://publications.scilifelab.se/researcher/1826b4a473304149a22a9646d6f76a3e.json"}}, {"family": "Geisheker", "given": "Madeleine R", "initials": "MR", "orcid": "0000-0002-4166-3236", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3494f8f657c4d0fbbd886ac89ac9cfa.json"}}, {"family": "Han", "given": "Lin", "initials": "L"}, {"family": "Du", "given": "Bing", "initials": "B"}, {"family": "Barnett", "given": "Chris", "initials": "C"}, {"family": "Thompson", "given": "Elizabeth", "initials": "E"}, {"family": "Shaw", "given": "Marie", "initials": "M"}, {"family": "Carroll", "given": "Renee", "initials": "R"}, {"family": "Friend", "given": "Kathryn", "initials": "K"}, {"family": "Catford", "given": "Rachael", "initials": "R"}, {"family": "Palmer", "given": "Elizabeth E", "initials": "EE"}, {"family": "Zou", "given": "Xiaobing", "initials": "X"}, {"family": "Ou", "given": "Jianjun", "initials": "J"}, {"family": "Li", "given": "Honghui", "initials": "H"}, {"family": "Guo", "given": "Hui", "initials": "H", "orcid": "0000-0002-1570-2545", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b7e6c55e24449fd9b53f6ed08003742.json"}}, {"family": "Gerdts", "given": "Jennifer", "initials": "J"}, {"family": "Avola", "given": "Emanuela", "initials": "E"}, {"family": "Calabrese", "given": "Giuseppe", "initials": "G"}, {"family": "Elia", "given": "Maurizio", "initials": "M"}, {"family": "Greco", "given": "Donatella", "initials": "D"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Vandeweyer", "given": "Geert", "initials": "G"}, {"family": "Van Dijck", "given": "Anke", "initials": "A", "orcid": "0000-0002-6713-2943", "researcher": {"href": "https://publications.scilifelab.se/researcher/b190da43c29e4245b71b37ab7cdb81db.json"}}, {"family": "Van der Aa", "given": "Nathalie", "initials": "N"}, {"family": "McKenna", "given": "Brooke", "initials": "B"}, {"family": "Hancarova", "given": "Miroslava", "initials": "M"}, {"family": "Bendova", "given": "Sarka", "initials": "S"}, {"family": "Havlovicova", "given": "Marketa", "initials": "M"}, {"family": "Malerba", "given": "Giovanni", "initials": "G"}, {"family": "Bernardina", "given": "Bernardo Dalla", "initials": "BD"}, {"family": "Muglia", "given": "Pierandrea", "initials": "P"}, {"family": "van Haeringen", "given": "Arie", "initials": "A"}, {"family": "Hoffer", "given": "Mariette J V", "initials": "MJV", "orcid": "0000-0002-1812-7670", "researcher": {"href": "https://publications.scilifelab.se/researcher/04747e9661474d43a1f4a7ed51eb7207.json"}}, {"family": "Franke", "given": "Barbara", "initials": "B", "orcid": "0000-0003-4375-6572", "researcher": {"href": "https://publications.scilifelab.se/researcher/105f0131cfc34a668ed840e622e4f902.json"}}, {"family": "Cappuccio", "given": "Gerarda", "initials": "G"}, {"family": "Delatycki", "given": "Martin", "initials": "M"}, {"family": "Lockhart", "given": "Paul J", "initials": "PJ", "orcid": "0000-0003-2531-8413", "researcher": {"href": "https://publications.scilifelab.se/researcher/af606d21d6524fbdbd65f044fddbd00b.json"}}, {"family": "Manning", "given": "Melanie A", "initials": "MA"}, {"family": "Liu", "given": "Pengfei", "initials": "P", "orcid": "0000-0002-4177-709X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8bda9fff7cc042eaa054b5257799c1f4.json"}}, {"family": "Scheffer", "given": "Ingrid E", "initials": "IE"}, {"family": "Brunetti-Pierri", "given": "Nicola", "initials": "N", "orcid": "0000-0002-6895-8819", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9785f9985d645259283e808cdcd77a9.json"}}, {"family": "Rommelse", "given": "Nanda", "initials": "N"}, {"family": "Amaral", "given": "David G", "initials": "DG"}, {"family": "Santen", "given": "Gijs W E", "initials": "GWE"}, {"family": "Trabetti", "given": "Elisabetta", "initials": "E"}, {"family": "Sedl\u00e1\u010dek", "given": "Zden\u011bk", "initials": "Z"}, {"family": "Michaelson", "given": "Jacob J", "initials": "JJ", "orcid": "0000-0001-9713-0992", "researcher": {"href": "https://publications.scilifelab.se/researcher/13cd0bf6a3c3437485c0c8c6a32839dc.json"}}, {"family": "Pierce", "given": "Karen", "initials": "K"}, {"family": "Courchesne", "given": "Eric", "initials": "E", "orcid": "0000-0002-3772-5799", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae6305c8ed044e1ca6b637f982d181c4.json"}}, {"family": "Kooy", "given": "R Frank", "initials": "RF", "orcid": "0000-0003-2024-0485", "researcher": {"href": "https://publications.scilifelab.se/researcher/d0e9d246a6ac47029258886b9537a0e5.json"}}, {"family": "SPARK Consortium", "given": "", "initials": ""}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Romano", "given": "Corrado", "initials": "C", "orcid": "0000-0003-1049-0683", "researcher": {"href": "https://publications.scilifelab.se/researcher/634b98b512e84042af68e05eff055978.json"}}, {"family": "Peeters", "given": "Hilde", "initials": "H"}, {"family": "Bernier", "given": "Raphael A", "initials": "RA"}, {"family": "Gecz", "given": "Jozef", "initials": "J", "orcid": "0000-0002-7884-6861", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfa0d2adb36840858e1f9f8e407269b0.json"}}, {"family": "Xia", "given": "Kun", "initials": "K", "orcid": "0000-0001-8090-6002", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbfe349e05c740a7894d1bab511a3768.json"}}, {"family": "Eichler", "given": "Evan E", "initials": "EE", "orcid": "0000-0002-8246-4014", "researcher": {"href": "https://publications.scilifelab.se/researcher/43901cc9fc3b4f5c9a18260e36558eb9.json"}}], "type": "journal article", "published": "2020-10-01", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4932", "issn-l": "2041-1723"}, "abstract": "Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.", "doi": "10.1038/s41467-020-18723-y", "pmid": "33004838", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18723-y"}, {"db": "pmc", "key": "PMC7530681"}], "notes": [], "created": "2021-11-20T12:18:30.540Z", "modified": "2021-11-20T12:18:31.111Z"}]}