Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer's disease neurons.
Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer's disease neurons.
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DOI：
10.1186/s13059-016-0976-2
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发表时间：
2016-05-31
期刊：
影响因子：
12.3
通讯作者：
Lansdorp PM
中科院分区：
文献类型：
--
作者：
van den Bos H;Spierings DC;Taudt AS;Bakker B;Porubský D;Falconer E;Novoa C;Halsema N;Kazemier HG;Hoekstra-Wakker K;Guryev V;den Dunnen WF;Foijer F;Tatché MC;Boddeke HW;Lansdorp PM
阿尔茨海默病（AD）是一种大脑神经退行性疾病，是老年人最常见的痴呆形式。非整倍体，一种细胞染色体数量异常的状态，被认为在阿尔茨海默病患者的神经变性中起作用。几项使用荧光原位杂交的研究表明，阿尔茨海默病患者的大脑含有更多的非整倍体细胞。然而，由于神经元中非整倍体的报道率范围很广，因此需要一种更灵敏的方法来确定非整倍体在AD病理中的可能作用。在目前的研究中，我们使用了一种新的单细胞全基因组测序（scWGS）方法来评估从正常对照个体（n = 6）和AD患者（n = 10）的额叶皮层分离的神经元的非整倍性。我们的方法的敏感性和特异性是通过在所有分析的唐氏综合症样本（n = 36）的神经元核中存在21号染色体的三个拷贝来证明的。在对照个体（n = 589）和AD患者（n = 893）的大脑中发现了非常低水平的非整倍体。与其他研究相反，我们观察到阿尔茨海默病患者神经元中17或21号染色体没有选择性增益。scWGS未显示正常和AD神经元存在共同的非整倍体。因此，我们的研究结果不支持神经细胞非整倍体在阿尔茨海默病发病机制中的重要作用。这需要在未来更大规模的研究中得到证实。本文的在线版本（doi:10.1186/s13059-016-0976-2）包含补充材料，可供授权用户使用。
Alzheimer’s disease (AD) is a neurodegenerative disease of the brain and the most common form of dementia in the elderly. Aneuploidy, a state in which cells have an abnormal number of chromosomes, has been proposed to play a role in neurodegeneration in AD patients. Several studies using fluorescence in situ hybridization have shown that the brains of AD patients contain an increased number of aneuploid cells. However, because the reported rate of aneuploidy in neurons ranges widely, a more sensitive method is needed to establish a possible role of aneuploidy in AD pathology. In the current study, we used a novel single-cell whole genome sequencing (scWGS) approach to assess aneuploidy in isolated neurons from the frontal cortex of normal control individuals (n = 6) and patients with AD (n = 10). The sensitivity and specificity of our method was shown by the presence of three copies of chromosome 21 in all analyzed neuronal nuclei of a Down’s syndrome sample (n = 36). Very low levels of aneuploidy were found in the brains from control individuals (n = 589) and AD patients (n = 893). In contrast to other studies, we observe no selective gain of chromosomes 17 or 21 in neurons of AD patients. scWGS showed no evidence for common aneuploidy in normal and AD neurons. Therefore, our results do not support an important role for aneuploidy in neuronal cells in the pathogenesis of AD. This will need to be confirmed by future studies in larger cohorts. The online version of this article (doi:10.1186/s13059-016-0976-2) contains supplementary material, which is available to authorized users.