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The annotation of has been concealed by its protein-coding pseudogene

Sci Adv. 2024-06; 
Emil K Gustavsson, Siddharth Sethi, Yujing Gao, Jonathan W Brenton, Sonia García-Ruiz, David Zhang, Raquel Garza, Regina H Reynolds, James R Evans, Zhongbo Chen, Melissa Grant-Peters, Hannah Macpherson, Kylie Montgomery, Rhys Dore, Anna I Wernick, Charles Arber, Selina Wray, Sonia Gandhi, Julian Esselborn, Cornelis Blauwendraat, Christopher H Douse, Anita Adami, Diahann A M Atacho, Antonina Kouli, Annelies Quaegebeur, Roger A Barker, Elisabet Englund, Frances Platt, Johan Jakobsson, Nicholas W Wood, Henry Houlden, Harpreet Saini, Carla F Bento, John Hardy, Mina Ryten
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摘要

Mutations in 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, . We show that >50% of short RNA-sequencing reads mapping to also map to . Thus, we used long-read RNA sequencing in the human brain, which allowed us to accurately quantify expression from both and . We discovered significant differences in expression compared to short-read data and identify currently unannotated transcripts of both and . 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 th... More

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