Increased contribution of non-reference alleles in mitochondrial DNA (mtDNA) of Alzheimer's disease (AD) patients. Homo sapiens

Many observations suggest that mutations of mtDNA could be responsible of the neurodegenerative changes associated with AD. We examined the signal intensity of the four alleles for each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls utilizing a resequencing array, the MitoChip v2.0, and identified 275 statistically different nps which all, with the exception of one, showed an increased contribution of non-reference alleles for AD patients. PCA and cluster analysis showed that 5 of these nps, characterized by low-level heteroplasmy, could discriminate AD from control subjects with 80% of cases correctly classified. Overall design: This study included a total of 18 AD patients and 18 age-matched controls. Data acquisition was performed using the Affymetrix Genechip Command Console (AGCC) software and data analysis was carried out with GSEQ 4.1.

大量研究证据表明，线粒体DNA（mtDNA）突变或与阿尔茨海默病（AD）相关的神经退行性病理改变存在因果关联。本研究采用重测序芯片MitoChip v2.0，对阿尔茨海默病患者与年龄匹配对照者的全血样本中每个线粒体DNA核苷酸位点（np）的四种等位基因信号强度进行检测，共鉴定出275个具有统计学差异的核苷酸位点；除1个位点外，其余所有位点均表现为阿尔茨海默病患者体内非参考等位基因的占比升高。主成分分析（PCA）与聚类分析结果显示，其中5个呈现低水平异质性的核苷酸位点可有效区分阿尔茨海默病患者与对照人群，分类准确率达80%。
实验整体设计：本研究共纳入18名阿尔茨海默病患者与18名年龄匹配的对照受试者。数据采集采用Affymetrix Genechip Command Console（AGCC）软件完成，数据分析则通过GSEQ 4.1软件进行。