The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1
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 G...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Association for the Advancement of Science
2024
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| _version_ | 1826315109145772032 |
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| author | Gustavsson, EK Sethi, S Gao, Y Brenton, JW García-Ruiz, S Zhang, D Garza, R Reynolds, RH Evans, JR Chen, Z Grant-Peters, M Macpherson, H Montgomery, K Dore, R Wernick, AI Arber, C Wray, S Gandhi, S Esselborn, J Blauwendraat, C Douse, CH Adami, A Atacho, DAM Kouli, A Quaegebeur, A Barker, RA Englund, E Platt, F Jakobsson, J Wood, NW Houlden, H Saini, H Bento, CF Hardy, J Ryten, M |
| author_facet | Gustavsson, EK Sethi, S Gao, Y Brenton, JW García-Ruiz, S Zhang, D Garza, R Reynolds, RH Evans, JR Chen, Z Grant-Peters, M Macpherson, H Montgomery, K Dore, R Wernick, AI Arber, C Wray, S Gandhi, S Esselborn, J Blauwendraat, C Douse, CH Adami, A Atacho, DAM Kouli, A Quaegebeur, A Barker, RA Englund, E Platt, F Jakobsson, J Wood, NW Houlden, H Saini, H Bento, CF Hardy, J Ryten, M |
| author_sort | Gustavsson, EK |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-12-09T03:20:02Z |
| format | Journal article |
| id | oxford-uuid:32e5dd84-b48f-43ad-89ee-e3ed7892db72 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:20:02Z |
| publishDate | 2024 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:32e5dd84-b48f-43ad-89ee-e3ed7892db722024-11-11T15:05:49ZThe annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:32e5dd84-b48f-43ad-89ee-e3ed7892db72EnglishSymplectic ElementsAmerican Association for the Advancement of Science2024Gustavsson, EKSethi, SGao, YBrenton, JWGarcía-Ruiz, SZhang, DGarza, RReynolds, RHEvans, JRChen, ZGrant-Peters, MMacpherson, HMontgomery, KDore, RWernick, AIArber, CWray, SGandhi, SEsselborn, JBlauwendraat, CDouse, CHAdami, AAtacho, DAMKouli, AQuaegebeur, ABarker, RAEnglund, EPlatt, FJakobsson, JWood, NWHoulden, HSaini, HBento, CFHardy, JRyten, MMutations 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. |
| spellingShingle | Gustavsson, EK Sethi, S Gao, Y Brenton, JW García-Ruiz, S Zhang, D Garza, R Reynolds, RH Evans, JR Chen, Z Grant-Peters, M Macpherson, H Montgomery, K Dore, R Wernick, AI Arber, C Wray, S Gandhi, S Esselborn, J Blauwendraat, C Douse, CH Adami, A Atacho, DAM Kouli, A Quaegebeur, A Barker, RA Englund, E Platt, F Jakobsson, J Wood, NW Houlden, H Saini, H Bento, CF Hardy, J Ryten, M The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1 |
| title | The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1 |
| title_full | The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1 |
| title_fullStr | The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1 |
| title_full_unstemmed | The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1 |
| title_short | The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1 |
| title_sort | annotation of gba1 has been concealed by its protein coding pseudogene gbap1 |
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