{"corpus_id":28744172,"paper_sha":"a097e30f6c040511bb59771239e7a66d03895d9f","doi":"10.1126/science.1154584","arxiv_id":null,"pmid":18309045,"pmcid":"PMC7116650","mag_id":1619082318,"dblp_id":null,"acl_id":null,"title":"TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis","year":2008,"publication_date":"2008-03-21","venue":"Science","journal":{"name":"Science","pages":"1668 - 1672","volume":"319"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":34,"citation_count":2605,"influential_citation_count":190,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Amino Acid Sequence","mj":false,"ui":"D000595"},{"d":"Amino Acid Substitution","mj":false,"ui":"D019943"},{"d":"Amyotrophic Lateral Sclerosis","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D000690"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Apoptosis","mj":false,"ui":"D017209"},{"d":"CHO Cells","mj":false,"ui":"D016466"},{"d":"Chick Embryo","mj":false,"ui":"D002642"},{"d":"Chromosomes, Human, Pair 1","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D002878"},{"d":"Cricetinae","mj":false,"ui":"D006224"},{"d":"Cricetulus","mj":false,"ui":"D003412"},{"d":"DNA-Binding Proteins","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D004268"},{"d":"Embryonic Development","mj":false,"ui":"D047108"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Microsatellite Repeats","mj":false,"ui":"D018895"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Molecular Sequence Data","mj":false,"ui":"D008969"},{"d":"Mutant Proteins","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D050505"},{"d":"Mutation, Missense","mj":true,"ui":"D020125"},{"d":"Neurons","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D009474"}],"chemicals":[{"n":"DNA-Binding Proteins","ui":"D004268","reg":"0"},{"n":"Mutant Proteins","ui":"D050505","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.science.org/cms/asset/43a68c57-63b4-4e65-a005-940851e99da2/pap.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/a097e30f6c040511bb59771239e7a66d03895d9f","s2_open_access_license":null,"s2_open_access_status":"GREEN","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.","claims":[{"public_id":"cl_755d119225b05dabf6bc631630e5de75","status":"active","text":"Mutant forms of TDP-43 fragmented more readily than wild type in vitro and induced neural apoptosis and developmental delay in chick embryos in vivo.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_755d119225b05dabf6bc631630e5de75"},{"public_id":"cl_bc22cb5d1bd472d911fc6e2794a3160d","status":"active","text":"Neighboring mutations in a highly conserved region of TARDBP were identified in both sporadic and familial amyotrophic lateral sclerosis cases.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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