A customized high-resolution array-comparative genomic hybridization to explore copy number variations in Parkinson’s disease

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• 作者：Valentina La Cognata ; Giovanna Morello ; Giulia Gentile ; Velia D’Agata…
• 关键词：aCGH ; CNVs ; Parkinson’s disease ; Neurological disorders ; Genes
• 刊名：neurogenetics
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：17
• 期：4
• 页码：233-244
• 全文大小：973 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Human Genetics
  Molecular Medicine
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1364-6753
• 卷排序：17

文摘

Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder, was long believed to be a non-genetic sporadic syndrome. Today, only a small percentage of PD cases with genetic inheritance patterns are known, often complicated by reduced penetrance and variable expressivity. The few well-characterized Mendelian genes, together with a number of risk factors, contribute to the major sporadic forms of the disease, thus delineating an intricate genetic profile at the basis of this debilitating and incurable condition. Along with single nucleotide changes, gene-dosage abnormalities and copy number variations (CNVs) have emerged as significant disease-causing mutations in PD. However, due to their size variability and to the quantitative nature of the assay, CNV genotyping is particularly challenging. For this reason, innovative high-throughput platforms and bioinformatics algorithms are increasingly replacing classical CNV detection methods. Here, we report the design strategy, development, validation and implementation of NeuroArray, a customized exon-centric high-resolution array-based comparative genomic hybridization (aCGH) tailored to detect single/multi-exon deletions and duplications in a large panel of PD-related genes. This targeted design allows for a focused evaluation of structural imbalances in clinically relevant PD genes, combining exon-level resolution with genome-wide coverage. The NeuroArray platform may offer new insights in elucidating inherited potential or de novo structural alterations in PD patients and investigating new candidate genes.