ORCID
- Mullin, Stephen: 0000-0002-1936-394X
Abstract
GBA variants carriers are at increased risk of Parkinson's disease (PD) and Lewy body dementia (LBD). The presence of pseudogene GBAP1 predisposes to structural variants, complicating genetic analysis. We present two methods to resolve recombinant alleles and other variants in GBA: Gauchian, a tool for short-read, whole-genome sequencing data analysis, and Oxford Nanopore sequencing after PCR enrichment. Both methods were concordant for 42 samples carrying a range of recombinants and GBAP1-related mutations, and Gauchian outperformed the GATK Best Practices pipeline. Applying Gauchian to sequencing of over 10,000 individuals shows that copy number variants (CNVs) spanning GBAP1 are relatively common in Africans. CNV frequencies in PD and LBD are similar to controls. Gains may coexist with other mutations in patients, and a modifying effect cannot be excluded. Gauchian detects more GBA variants in LBD than PD, especially severe ones. These findings highlight the importance of accurate GBA analysis in these patients.
DOI
10.1038/s42003-022-03610-7
Publication Date
2022-07-06
Publication Title
Commun Biol
Volume
5
Issue
1
Embargo Period
2022-07-22
Organisational Unit
Peninsula Medical School
Keywords
Alleles, Glucosylceramidase, Heterozygote, Humans, Lewy Body Disease, Parkinson Disease
First Page
670
Last Page
670
Recommended Citation
Toffoli, M., Chen, X., Sedlazeck, F., Lee, C., Mullin, S., Higgins, A., Koletsi, S., Garcia-Segura, M., Sammler, E., Scholz, S., Schapira, A., Eberle, M., & Proukakis, C. (2022) 'Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson's disease-associated GBA gene.', Commun Biol, 5(1), pp. 670-670. Available at: https://doi.org/10.1038/s42003-022-03610-7
