eprintid: 10102309 rev_number: 23 eprint_status: archive userid: 608 dir: disk0/10/10/23/09 datestamp: 2020-06-24 12:03:16 lastmod: 2021-12-21 23:10:40 status_changed: 2020-06-24 12:03:16 type: article metadata_visibility: show creators_name: Zhang, D creators_name: Guelfi, S creators_name: Garcia-Ruiz, S creators_name: Costa, B creators_name: Reynolds, RH creators_name: D’Sa, K creators_name: Liu, W creators_name: Courtin, T creators_name: Peterson, A creators_name: Jaffe, AE creators_name: Hardy, J creators_name: Botía, JA creators_name: Collado-Torres, L creators_name: Ryten, M title: Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders ispublished: pub subjects: UCH divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 divisions: C08 divisions: D10 divisions: G10 divisions: D13 divisions: G23 note: This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. abstract: Growing evidence suggests that human gene annotation remains incomplete; however, it is unclear how this affects different tissues and our understanding of different disorders. Here, we detect previously unannotated transcription from Genotype-Tissue Expression RNA sequencing data across 41 human tissues. We connect this unannotated transcription to known genes, confirming that human gene annotation remains incomplete, even among well-studied genes including 63% of the Online Mendelian Inheritance in Man–morbid catalog and 317 neurodegeneration-associated genes. We find the greatest abundance of unannotated transcription in brain and genes highly expressed in brain are more likely to be reannotated. We explore examples of reannotated disease genes, such as SNCA, for which we experimentally validate a previously unidentified, brain-specific, potentially protein-coding exon. We release all tissue-specific transcriptomes through vizER: http://rytenlab.com/browser/app/vizER. We anticipate that this resource will facilitate more accurate genetic analysis, with the greatest impact on our understanding of Mendelian and complex neurogenetic disorders. date: 2020-06-10 date_type: published official_url: https://doi.org/10.1126/sciadv.aay8299 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1791482 doi: 10.1126/sciadv.aay8299 lyricists_name: Hardy, John lyricists_name: Liu, Wenfei lyricists_name: Reynolds, Regina lyricists_name: Ryten, Mina lyricists_name: Smalley, June lyricists_name: Zhang, David lyricists_id: JHARD28 lyricists_id: WLIUX92 lyricists_id: RHREY66 lyricists_id: MBARI42 lyricists_id: JASMA87 lyricists_id: DZHAN63 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Science Advances volume: 6 number: 24 article_number: eaay8299 citation: Zhang, D; Guelfi, S; Garcia-Ruiz, S; Costa, B; Reynolds, RH; D’Sa, K; Liu, W; ... Ryten, M; + view all <#> Zhang, D; Guelfi, S; Garcia-Ruiz, S; Costa, B; Reynolds, RH; D’Sa, K; Liu, W; Courtin, T; Peterson, A; Jaffe, AE; Hardy, J; Botía, JA; Collado-Torres, L; Ryten, M; - view fewer <#> (2020) Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders. Science Advances , 6 (24) , Article eaay8299. 10.1126/sciadv.aay8299 <https://doi.org/10.1126/sciadv.aay8299>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10102309/1/eaay8299.full.pdf