The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1
(2024) In Science Advances 10(26). p.1-20- 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... (More)
- 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. (Less)
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- author
- organization
- publishing date
- 2024-06-28
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science Advances
- volume
- 10
- issue
- 26
- pages
- 1 - 20
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- pmid:38924406
- ISSN
- 2375-2548
- DOI
- 10.1126/sciadv.adk1296
- language
- English
- LU publication?
- yes
- id
- 1bd86ba8-32fe-42f2-bfc1-db96a69ef7ac
- date added to LUP
- 2024-06-28 11:22:39
- date last changed
- 2024-07-01 09:02:40
@article{1bd86ba8-32fe-42f2-bfc1-db96a69ef7ac, 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.}}, author = {{Gustavsson, Emil K. and Sethi, Siddharth and Gao, Yujing and Brenton, Jonathan W. and García-Ruiz, Sonia and Zhang, David and Garza, Raquel and Reynolds, Regina H. and Evans, James R. and Chen, Zhongbo and Grant-Peters, Melissa and Macpherson, Hannah and Montgomery, Kylie and Dore, Rhys and Wernick, Anna i. and Arber, Charles and Wray, Selina and Gandhi, Sonia and Esselborn, Julian and Blauwendraat, Cornelis and Douse, Christopher H. and Adami, Anita and Atacho, Diahann A. M. and Kouli, Antonina and Quaegebeur, Annelies and Barker, Roger A. and Englund, Elisabet and Platt, Frances and Jakobsson, Johan and Wood, Nicholas W. and Houlden, Henry and Saini, Harpreet and Bento, Carla F. and Hardy, John and Ryten, Mina}}, issn = {{2375-2548}}, language = {{eng}}, month = {{06}}, number = {{26}}, pages = {{1--20}}, publisher = {{American Association for the Advancement of Science (AAAS)}}, series = {{Science Advances}}, title = {{The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1}}, url = {{http://dx.doi.org/10.1126/sciadv.adk1296}}, doi = {{10.1126/sciadv.adk1296}}, volume = {{10}}, year = {{2024}}, }