Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson's disease-associated GBA gene

Marco Toffoli, Xiao Chen, Fritz J. Sedlazeck, Chiao-Yin Lee, Stephen Mullin, Abigail Higgins, Sofia Koletsi, Monica Emili Garcia-Segura, Esther Sammler, Sonja W. Scholz, Anthony H. V. Schapira, Michael A. Eberle (Lead / Corresponding author), Christos Proukakis (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
23 Downloads (Pure)


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.

Original languageEnglish
Article number670
Number of pages10
JournalCommunications Biology
Publication statusPublished - 6 Jul 2022


  • Alleles
  • Glucosylceramidase/genetics
  • Heterozygote
  • Humans
  • Lewy Body Disease/genetics
  • Parkinson Disease/genetics

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry,Genetics and Molecular Biology
  • Medicine (miscellaneous)


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