Lobon Irene, Solís-Moruno Manuel, Juan David, Muhaisen Ashraf, Abascal Federico, Esteller-Cucala Paula, García-Pérez Raquel, Martí Maria Josep, Tolosa Eduardo, Ávila Jesús, Rahbari Raheleh, Marques-Bonet Tomas, Casals Ferran, Soriano Eduardo
Institute of Evolutionary Biology (UPF-CSIC), Barcelona, Spain.
Genomics Core Facility, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Front Aging. 2022 Apr 28;3:851039. doi: 10.3389/fragi.2022.851039. eCollection 2022.
The role of somatic mutations in complex diseases, including neurodevelopmental and neurodegenerative disorders, is becoming increasingly clear. However, to date, no study has shown their relation to Parkinson disease's phenotype. To explore the relevance of embryonic somatic mutations in sporadic Parkinson disease, we performed whole-exome sequencing in blood and four brain regions of ten patients. We identified 59 candidate somatic single nucleotide variants (sSNVs) through sensitive calling and a careful filtering strategy (COSMOS). We validated 27 of them with amplicon-based ultra-deep sequencing, with a 70% validation rate for the highest-confidence variants. The identified sSNVs are in genes with synaptic functions that are co-expressed with genes previously associated with Parkinson disease. Most of the sSNVs were only called in blood but were also found in the brain tissues with ultra-deep amplicon sequencing, demonstrating the strength of multi-tissue sampling designs.
体细胞突变在包括神经发育障碍和神经退行性疾病在内的复杂疾病中的作用日益明晰。然而，迄今为止，尚无研究表明它们与帕金森病表型的关系。为探究胚胎体细胞突变在散发性帕金森病中的相关性，我们对10名患者的血液和四个脑区进行了全外显子组测序。通过灵敏的检测和细致的过滤策略（COSMOS），我们鉴定出59个候选体细胞单核苷酸变异（sSNV）。我们用基于扩增子的超深度测序验证了其中27个，最高置信度变异的验证率为70%。鉴定出的sSNV存在于具有突触功能的基因中，这些基因与先前与帕金森病相关的基因共表达。大多数sSNV仅在血液中检测到，但在脑组织的超深度扩增子测序中也被发现，这证明了多组织采样设计的优势。
