Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson's disease-associated GBA gene.
Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson's disease-associated GBA gene.
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DOI：
10.1038/s42003-022-03610-7
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发表时间：
2022-07-06
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
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GBA变异携带者患帕金森病（PD）和路易体痴呆（LBD）的风险增加。假基因GBAP1的存在易导致结构变异，使遗传分析复杂化。我们提出了两种方法来分析GBA中的重组等位基因和其他变异：Gauchian（一种用于短读全基因组测序数据分析的工具）和PCR富集后的Oxford Nanopore测序。这两种方法在42个携带一系列重组体和gbap1相关突变的样本中是一致的，并且Gauchian的表现优于GATK Best Practices管道。将Gauchian基因应用于1万多个个体的测序表明，跨越GBAP1的拷贝数变异（CNVs）在非洲人中相对普遍。PD和LBD的CNV频率与对照组相似。增益可能与患者的其他突变共存，不能排除修饰作用。Gauchian在LBD中检测到比PD更多的GBA变异，尤其是严重的。这些发现强调了对这些患者进行准确GBA分析的重要性。有两种方法可以完全解析GBA基因：Gauchian（一种用于短读全基因组测序数据分析的工具）和PCR富集后的Oxford Nanopore测序。该方法提高了我们对GBA、戈谢病和帕金森病之间关系的认识。
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. Two methods fully resolve the GBA gene: Gauchian, a tool for short-read, whole-genome sequencing data analysis, and Oxford Nanopore sequencing after PCR enrichment. The approach improves our understanding of the relationship between GBA, Gaucher disease and Parkinson disease.
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影响因子：
23.8
作者：
Luo, Ruibang;Wong, Chak-Lim;Lam, Tak-Wah
通讯作者：
Lam, Tak-Wah
影响因子：
30.8
作者：
Chia R;Sabir MS;Bandres-Ciga S;Saez-Atienzar S;Reynolds RH;Gustavsson E;Walton RL;Ahmed S;Viollet C;Ding J;Makarious MB;Diez-Fairen M;Portley MK;Shah Z;Abramzon Y;Hernandez DG;Blauwendraat C;Stone DJ;Eicher J;Parkkinen L;Ansorge O;Clark L;Honig LS;Marder K;Lemstra A;St George-Hyslop P;Londos E;Morgan K;Lashley T;Warner TT;Jaunmuktane Z;Galasko D;Santana I;Tienari PJ;Myllykangas L;Oinas M;Cairns NJ;Morris JC;Halliday GM;Van Deerlin VM;Trojanowski JQ;Grassano M;Calvo A;Mora G;Canosa A;Floris G;Bohannan RC;Brett F;Gan-Or Z;Geiger JT;Moore A;May P;Krüger R;Goldstein DS;Lopez G;Tayebi N;Sidransky E;American Genome Center;Norcliffe-Kaufmann L;Palma JA;Kaufmann H;Shakkottai VG;Perkins M;Newell KL;Gasser T;Schulte C;Landi F;Salvi E;Cusi D;Masliah E;Kim RC;Caraway CA;Monuki ES;Brunetti M;Dawson TM;Rosenthal LS;Albert MS;Pletnikova O;Troncoso JC;Flanagan ME;Mao Q;Bigio EH;Rodríguez-Rodríguez E;Infante J;Lage C;González-Aramburu I;Sanchez-Juan P;Ghetti B;Keith J;Black SE;Masellis M;Rogaeva E;Duyckaerts C;Brice A;Lesage S;Xiromerisiou G;Barrett MJ;Tilley BS;Gentleman S;Logroscino G;Serrano GE;Beach TG;McKeith IG;Thomas AJ;Attems J;Morris CM;Palmer L;Love S;Troakes C;Al-Sarraj S;Hodges AK;Aarsland D;Klein G;Kaiser SM;Woltjer R;Pastor P;Bekris LM;Leverenz JB;Besser LM;Kuzma A;Renton AE;Goate A;Bennett DA;Scherzer CR;Morris HR;Ferrari R;Albani D;Pickering-Brown S;Faber K;Kukull WA;Morenas-Rodriguez E;Lleó A;Fortea J;Alcolea D;Clarimon J;Nalls MA;Ferrucci L;Resnick SM;Tanaka T;Foroud TM;Graff-Radford NR;Wszolek ZK;Ferman T;Boeve BF;Hardy JA;Topol EJ;Torkamani A;Singleton AB;Ryten M;Dickson DW;Chiò A;Ross OA;Gibbs JR;Dalgard CL;Traynor BJ;Scholz SW
通讯作者：
Scholz SW
影响因子：
9.9
作者：
Alcalay, R. N.;Caccappolo, E.;Marder, K.
通讯作者：
Marder, K.
影响因子：
2.6
作者：
Higgins, Abigail Louise;Toffoli, Marco;Schapira, Anthony H., V
通讯作者：
Schapira, Anthony H., V
影响因子：
14.5
作者：
Blauwendraat, Cornelis;Reed, Xylena;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.