Absence of coding somatic single nucleotide variants within well-known candidate genes in late-onset sporadic Alzheimer's Disease based on the analysis of multi-omics data,Neurobiology of Aging

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Absence of coding somatic single nucleotide variants within well-known candidate genes in late-onset sporadic Alzheimer's Disease based on the analysis of multi-omics data
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2021-07-21 , DOI: 10.1016/j.neurobiolaging.2021.07.010
Shishi Min ₁ , Zongchang Li ₂ , Annie Shieh ₃ , Gina Giase ₄ , Riyue Bao ₅ , Chunling Zhang ₆ , Liz Kuney ₃ , Richard Kopp ₃ , Huma Asif ₇ , Ney Alliey-Rodriguez ₇ , Lixia Qin ₈ , David Wesley Craig ₉ , Geoffrey J Faulkner ₁₀ , Elliot S Gershon ₁₁ , Beisha Tang ₁₂ , Chao Chen ₁₃ , Chunyu Liu ₁₄

Affiliation

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences; Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences; Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Psychiatry and Behavioral Neurosciences, University of Chicago, Chicago, IL, USA.
Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
School of Public Health, University of Illinois at Chicago, Chicago, IL, USA.
UPMC Hillman Cancer Center Cancer, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Neuroscience & Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
Department of Psychiatry and Behavioral Neurosciences, University of Chicago, Chicago, IL, USA.
Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, Australia; Queensland Brain Institute, University of Queensland, Brisbane, Australia.
Department of Psychiatry and Behavioral Neurosciences, University of Chicago, Chicago, IL, USA; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders (Xiangya), Changsha, Hunan, China.
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences; Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences; Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA; School of Psychology, Shaanxi Normal University, Xi'an, Shaanxi, China.

Somatic mutations arise randomly or are induced by environmental factors, which may increase the risk of Alzheimer's disease (AD). Identifying somatic mutations in sporadic AD (SAD) may provide new insight of the disease. To evaluate the potential contribution of somatic single nucleotide variations (SNVs), particularly that of well-known AD-candidate genes, we investigated sequencing data sets from four platforms: whole-genome sequencing (WGS), deep whole-exome sequencing (WES) on paired brain and liver samples, RNA sequencing (RNA-seq), and single-cell whole-genome sequencing (scWGS) of brain samples from 16 AD patients and 16 non-AD individuals. We found that the average number, mean variant allele fractions (VAFs) and mutational signatures of somatic SNVs have similar distributions between AD brains and non-AD brains. We did not identify any somatic SNVs within coding regions of the APP, PSEN1, PSEN2, nor in APOE. This study shows that somatic SNVs within the coding region of AD-candidate genes are unlikely to be a common causal factor for SAD.

中文翻译：

基于多组学数据分析，迟发性散发性阿尔茨海默病中众所周知的候选基因中缺乏编码体细胞单核苷酸变异

体细胞突变随机发生或由环境因素诱导，这可能会增加阿尔茨海默病 (AD) 的风险。识别散发性 AD (SAD) 中的体细胞突变可能会提供对该疾病的新认识。为了评估体细胞单核苷酸变异 (SNV) 的潜在贡献，尤其是众所周知的 AD 候选基因的潜在贡献，我们调查了来自四个平台的测序数据集：全基因组测序 (WGS)、深度全外显子组测序 (WES)对来自 16 名 AD 患者和 16 名非 AD 个体的大脑样本进行配对的大脑和肝脏样本、RNA 测序 (RNA-seq) 和单细胞全基因组测序 (scWGS)。我们发现体细胞 SNV 的平均数量、平均变异等位基因分数 (VAF) 和突变特征在 AD 大脑和非 AD 大脑之间具有相似的分布。APP、PSEN1、PSEN2，也不在APOE中。这项研究表明，AD 候选基因编码区内的体细胞 SNV 不太可能是 SAD 的常见致病因素。

更新日期：2021-07-22

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