A customized Comparative Genomic Hybridization array for the analysis of Copy Number Variations and exon-dosage anomalies in neurological disorders

Neurological disorders are a highly heterogeneous group of pathological conditions characterized by multifactorial etiology relying on genetics, epigenetics and/or environmental contributions. The very complex nature of this group of diseases makes the investigation of their genetic basis rather difficult, mostly if performed gene by gene through traditional methodological approaches. For this reason, high-throughput genotyping technologies are increasingly replacing the classical detection methods, providing higher resolution and a complete window of candidate genomic anomalies. Among the advanced biotechnologies, microarray-based comparative genomic hybridization (aCGH) represents a powerful molecular tool to explore the pathogenetic role of unbalanced structural rearrangements, also in a diagnostic setting. Here, we report the design strategy, development, validation, and implementation of NeuroArray, an exon-centric customized aCGH tailored to detect single/multi-exon deletions and duplications in a large panel of multi- and monogenic neurological disorders. This targeted design allows a focused evaluation of structural imbalances in clinically relevant genes at exon-level resolution. An increasing use of the NeuroArray platform may offer new insights in investigating potential overlapping gene signatures among neurological conditions and defining genotype-phenotype relationships.