TY  - JOUR
UR  - https://doi.org/10.1038/s42003-022-03610-7
TI  - Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson's disease-associated GBA gene
KW  - Disease genetics
KW  -  Parkinson's disease
N1  - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article?s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article?s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
SN  - 2399-3642
ID  - discovery10152057
AV  - public
JF  - Communications Biology
N2  - 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.
A1  - Toffoli, Marco
A1  - Chen, Xiao
A1  - Sedlazeck, Fritz J
A1  - Lee, Chiao-Yin
A1  - Mullin, Stephen
A1  - Higgins, Abigail
A1  - Koletsi, Sofia
A1  - Garcia-Segura, Monica Emili
A1  - Sammler, Esther
A1  - Scholz, Sonja W
A1  - Schapira, Anthony HV
A1  - Eberle, Michael A
A1  - Proukakis, Christos
VL  - 5
Y1  - 2022/07/06/
ER  -