JSON
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
Sci Adv 10 (26) eadk1296 [2024-06-28; online 2024-06-26]
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.
Clinical Genomics Lund [Service]
PubMed 38924406
DOI 10.1126/sciadv.adk1296
Crossref 10.1126/sciadv.adk1296