The expression of GBA and its pseudogene GBAP1 in different human tissues

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GBA gene is a human gene located in the long arm of chromosome 1 encoding for Glucocerebrosidase (GCase), which is a lysosomal enzyme involved in the metabolism of glucosylceramide (GlcCer) to ceramide and glucose. Mutations in GBA gene cause Gaucher disease (GD) when biallelic and are strong risk factors for Parkinson's disease (PD) when heterozygous. The genomic analyses of GBA have been historically complicated by the presence of a highly homologous pseudogene (GBAP1), which shares 96% sequence homology with GBA. However, the advancement of long-read sequencing technology has enabled more accurate analysis and thereby facilitated the discovery of novel GBA transcripts by long-read RNA-seq in the Ryten lab, and this data formed the basis of this thesis. Furthermore, the advancement of RNA-Seq technologies has enabled the quantification of expressed pseudogenes such as GBAP1 and uncovered its potential regulatory functions that could be targeted for therapeutic purposes. In this thesis, publicly available RNA-seq data were bioinformatically reanalyzed and showed significant results supporting the correlation of GBA and GBAP1 expression across different anatomical regions with strongest correlation and highest expression of GBAP1 in brain tissues. These findings could prompt further investigations into the link between GBA, GBAP1, and PD. Additionally, I attempted to experimentally validate GBA exons identified by long-read seq-data within novel transcripts, and demonstrated their expression with varying levels across different human tissues. However, further studies are needed to validate these results.