Background: Copy Number Variants (CNVs) represent a prevailing type of structural variation (deletions or duplications) in the human genome. In the last few years, several studies have demonstrated that CNVs represent significant mutations in Alzheimer’s Disease (AD) hereditability. Currently, innovative high-throughput platforms and bioinformatics algorithms are spreading to screening CNVs involved in different neurological diseases. In particular, the use of custom arrays, based on libraries of probes that can detect significant genomic regions, have greatly improved the resolution of targeted regions and the identification of chromosomal aberrations. Objective: In this work, we report the use of NeuroArray, a custom CGH microarray useful to screening and further investigate the role of the recurring genomic aberrations in patients with confirmed or suspected AD. Methods: The custom oligonucleotide aCGH design includes 641 genes and 9118 exons, linked to AD. The genomic DNA was isolated from blood samples of AD affected patients. The entire protocol of custom NeuroArray included digestion, labelling and hybridization steps as a standard aCGH assay. Results: The NeuroArray analysis revealed the presence of amplifications in several genes associated with AD. In the coding regions of these genes, 14,586 probes were designed with a 348 bp median probe spacing. The majority of targeted AD genes map on chromosomes 1 and 10. A significant aspect of the NeuroArray design is that 95% of the total exon targets is covered by at least one probe, a resolution higher than CGH array platforms commercially available. Conclusion: By identifying with a high sensitivity the chromosomal abnormalities in a large panel of AD-related genes and other neurological diseases, the NeuroArray platform is a valid tool for clinical diagnosis.

中文翻译：

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NeuroArray，一种用于破译阿尔茨海默病拷贝数变异的定制 CGH 微阵列

背景：拷贝数变异（CNV）代表了人类基因组中一种普遍存在的结构变异（缺失或重复）。在过去几年中，多项研究表明 CNV 代表阿尔茨海默病 (AD) 遗传力的显着突变。目前，创新的高通量平台和生物信息学算法正在扩展到筛选涉及不同神经系统疾病的CNV。特别是，使用基于可以检测重要基因组区域的探针库的定制阵列，极大地提高了目标区域的分辨率和染色体畸变的识别。目的：在这项工作中，我们报告了 NeuroArray 的使用，一种定制的 CGH 微阵列，可用于筛查和进一步研究复发性基因组畸变在确诊或疑似 AD 患者中的作用。方法：定制的寡核苷酸 aCGH 设计包括 641 个基因和 9118 个外显子，与 AD 相关。从受 AD 影响的患者的血液样本中分离出基因组 DNA。定制 NeuroArray 的整个方案包括作为标准 aCGH 测定的消化、标记和杂交步骤。结果：NeuroArray 分析揭示了与 AD 相关的几个基因中存在扩增。在这些基因的编码区，设计了 14,586 个探针，探针间距中值为 348 bp。大多数靶向 AD 基因位于 1 号和 10 号染色体上。NeuroArray 设计的一个重要方面是总外显子目标的 95% 被至少一个探针覆盖，分辨率高于市售的 CGH 阵列平台。结论：通过以高灵敏度识别大量 AD 相关基因和其他神经系统疾病中的染色体异常，NeuroArray 平台是临床诊断的有效工具。