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The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1.
Gustavsson, Emil K; Sethi, Siddharth; Gao, Yujing; Brenton, Jonathan W; García-Ruiz, Sonia; Zhang, David; Garza, Raquel; Reynolds, Regina H; Evans, James R; Chen, Zhongbo; Grant-Peters, Melissa; Macpherson, Hannah; Montgomery, Kylie; Dore, Rhys; Wernick, Anna I; Arber, Charles; Wray, Selina; Gandhi, Sonia; Esselborn, Julian; Blauwendraat, Cornelis; Douse, Christopher H; Adami, Anita; Atacho, Diahann A M; Kouli, Antonina; Quaegebeur, Annelies; Barker, Roger A; Englund, Elisabet; Platt, Frances; Jakobsson, Johan; Wood, Nicholas W; Houlden, Henry; Saini, Harpreet; Bento, Carla F; Hardy, John; Ryten, Mina.
Affiliation
  • Gustavsson EK; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Sethi S; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
  • Gao Y; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Brenton JW; Astex Pharmaceuticals, 436 Cambridge Science Park, Cambridge, UK.
  • García-Ruiz S; Astex Pharmaceuticals, 436 Cambridge Science Park, Cambridge, UK.
  • Zhang D; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Garza R; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
  • Reynolds RH; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Evans JR; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.
  • Chen Z; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Grant-Peters M; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund, Sweden.
  • Macpherson H; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Montgomery K; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
  • Dore R; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
  • Wernick AI; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Arber C; The Francis Crick Institute, London, UK.
  • Wray S; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Gandhi S; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Esselborn J; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
  • Blauwendraat C; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Douse CH; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Adami A; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Atacho DAM; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Kouli A; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Quaegebeur A; The Francis Crick Institute, London, UK.
  • Barker RA; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Englund E; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Platt F; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
  • Jakobsson J; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Wood NW; The Francis Crick Institute, London, UK.
  • Houlden H; Astex Pharmaceuticals, 436 Cambridge Science Park, Cambridge, UK.
  • Saini H; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bento CF; Laboratory of Epigenetics and Chromatin Dynamics, Department of Experimental Medical Science, Lund Stem Cell Center, Lund University, Lund, Sweden.
  • Hardy J; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund, Sweden.
  • Ryten M; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund, Sweden.
Sci Adv ; 10(26): eadk1296, 2024 Jun 28.
Article in En | MEDLINE | ID: mdl-38924406
ABSTRACT
Mutations in GBA1 cause Gaucher disease and are the most important genetic risk factor for Parkinson's disease. However, analysis of transcription at this locus is complicated by its highly homologous pseudogene, GBAP1. We show that >50% of short RNA-sequencing reads mapping to GBA1 also map to GBAP1. Thus, we used long-read RNA sequencing in the human brain, which allowed us to accurately quantify expression from both GBA1 and GBAP1. We discovered significant differences in expression compared to short-read data and identify currently unannotated transcripts of both GBA1 and GBAP1. These included protein-coding transcripts from both genes that were translated in human brain, but without the known lysosomal function-yet accounting for almost a third of transcription. Analyzing brain-specific cell types using long-read and single-nucleus RNA sequencing revealed region-specific variations in transcript expression. Overall, these findings suggest nonlysosomal roles for GBA1 and GBAP1 with implications for our understanding of the role of GBA1 in health and disease.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pseudogenes / Glucosylceramidase Limits: Humans Language: En Journal: Sci Adv Year: 2024 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pseudogenes / Glucosylceramidase Limits: Humans Language: En Journal: Sci Adv Year: 2024 Document type: Article Affiliation country: