NeuroArray: A Customized aCGH for the Analysis of Copy Number Variations in Neurological Disorders

Background: Neurological disorders are a highly heterogeneous group of pathological conditions that affect both the peripheral and the central nervous system. These pathologies are characterized by a complex and multifactorial etiology involving numerous environmental agents and genetic susceptibility factors. For this reason, the investigation of their pathogenetic basis by means of traditional methodological approaches is rather arduous. High-throughput genotyping technologies, including the microarray-based comparative genomic hybridization (aCGH), are currently replacing classical detection methods, providing powerful molecular tools to identify genomic unbalanced structural rearrangements and explore their role in the pathogenesis of many complex human diseases. Methods: In this report, we comprehensively describe the design method, the procedures, validation, and implementation of an exon-centric customized aCGH (NeuroArray 1.0), tailored to detect both single and multi-exon deletions or duplications in a large set of multi- and monogenic neurological diseases. This focused platform enables a targeted measurement of structural imbalances across the human genome, targeting the clinically relevant genes at exon-level resolution. Conclusion: 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.

• Publication year

  2018

• Venue

  Current Genomics

• Publication date

  2018-07-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.2174/1389202919666180404105451PMID 30258275PMCID 6128384
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Genetics of Parkinson's disease

  2018cited by this paper
• Identification of novel candidate disease genes from de novo exonic copy number variants

  2017cited by this paper
• Copy Number Variations in Amyotrophic Lateral Sclerosis: Piecing the Mosaic Tiles Together through a Systems Biology Approach

  2017cited by this paper
• Copy number variations in sporadic amyotrophic lateral sclerosis

  2017influential reference
• Copy number variations and stroke

  2016influential reference
• The importance of genetic diagnosis for Duchenne muscular dystrophy

  2016cited by this paper
• A customized high-resolution array-comparative genomic hybridization to explore copy number variations in Parkinson’s disease

  2016influential reference
• Application of whole‐exome sequencing for detecting copy number variants in CMT1A/HNPP

  2016cited by this paper
• Spinocerebellar ataxia: relationship between phenotype and genotype – a review

  2016cited by this paper
• Enhanced copy number variants detection from whole-exome sequencing data using EXCAVATOR2

  2016cited by this paper
• Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks

  2016cited by this paper
• Copy Number Variants in Alzheimer’s Disease

  2016cited by this paper
• Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders

  2016cited by this paper
• Cutaneous manifestations in neuro-oncology: clinically relevant tumor and treatment associated dermatologic findings.

  2016cited by this paper
• Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype

  2016cited by this paper
• Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

  2016cited by this paper
• Clinical exome sequencing in neurogenetic and neuropsychiatric disorders

  2016cited by this paper
• A copy number variation map of the human genome

  2015cited by this paper
• Copy Number Variations in a Population-Based Study of Charcot-Marie-Tooth Disease

  2015cited by this paper
• De novo deleterious genetic variations target a biological network centered on Aβ peptide in early-onset Alzheimer disease

  2015cited by this paper
• Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy

  2015cited by this paper
• Genetic overlap between Alzheimer’s disease and Parkinson’s disease at the MAPT locus

  2015cited by this paper
• Duchenne Muscular Dystrophy: From Diagnosis to Therapy

  2015cited by this paper
• Splicing: is there an alternative contribution to Parkinson’s disease?

  2015cited by this paper
• Molecular classification of amyotrophic lateral sclerosis by unsupervised clustering of gene expression in motor cortex.

  2015cited by this paper
• Frontotemporal dementia.

  2015cited by this paper
• Alternative Splicing Generates Different Parkin Protein Isoforms: Evidences in Human, Rat, and Mouse Brain

  2014cited by this paper
• Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10 362 consecutive cases

  2014cited by this paper
• The hidden genetics of epilepsy—a clinically important new paradigm

  2014cited by this paper
• Copy number variation plays an important role in clinical epilepsy

  2014cited by this paper
• Genetic testing in the epilepsies—developments and dilemmas

  2014cited by this paper
• Rare autosomal copy number variations in early-onset familial Alzheimer’s disease

  2014influential reference
• A 6.4 Mb duplication of the α-synuclein locus causing frontotemporal dementia and Parkinsonism: phenotype-genotype correlations.

  2014cited by this paper
• Recent advances in Charcot-Marie-Tooth disease.

  2014cited by this paper
• Charcot-Marie-Tooth Disease and Other Inherited Neuropathies

  2014cited by this paper
• Increasing the Coding Potential of Genomes Through Alternative Splicing: The Case of PARK2 Gene

  2014cited by this paper
• Assessing copy number from exome sequencing and exome array CGH based on CNV spectrum in a large clinical cohort

  2014cited by this paper
• Genetic basis of limb-girdle muscular dystrophies: the 2014 update

  2014cited by this paper
• Sporadic NF1 mutation associated with a de-novo 20q11.3 deletion explains the association of unusual facies, Moyamoya vasculopathy, and developmental delay, reported by Bertoli et al. in 2009.

  2013cited by this paper
• Current analysis platforms and methods for detecting copy number variation.

  2013cited by this paper
• Single exon-resolution targeted chromosomal microarray analysis of known and candidate intellectual disability genes

  2013cited by this paper
• Custom oligonucleotide array-based CGH: a reliable diagnostic tool for detection of exonic copy-number changes in multiple targeted genes

  2013cited by this paper
• High‐Resolution Survey in Familial Parkinson Disease Genes Reveals Multiple Independent Copy Number Variation Events in PARK2

  2013cited by this paper
• Customized high resolution CGH‐array for clinical diagnosis reveals additional genomic imbalances in previous well‐defined pathological samples

  2013cited by this paper
• Targeted next generation sequencing as a diagnostic tool in epileptic disorders

  2012cited by this paper
• Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders

  2012cited by this paper
• Genetics of Parkinson's disease.

  2012cited by this paper
• Role of mendelian genes in "sporadic" Parkinson's disease.

  2012cited by this paper
• Advances in Epilepsy Genetics and Genomics

  2012cited by this paper
• Analysis of Copy Number Variation in Alzheimer’s Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals

  2012cited by this paper
• From Genetics to Genomics of Epilepsy

  2012cited by this paper
• Analysis of copy number variation in Alzheimer's disease: the NIALOAD/ NCRAD Family Study.

  2012cited by this paper
• The PMP22 Gene and Its Related Diseases

  2012influential reference
• Application of custom-designed oligonucleotide array CGH in 145 patients with autistic spectrum disorders

  2012cited by this paper
• Targeted array CGH as a valuable molecular diagnostic approach: experience in the diagnosis of mitochondrial and metabolic disorders.

  2012cited by this paper
• Copy number variations in neurodevelopmental disorders.

  2012cited by this paper
• Utility of array CGH in molecular diagnosis of mitochondrial disorders.

  2012cited by this paper
• Identification of recurrent type‐2 NF1 microdeletions reveals a mitotic nonallelic homologous recombination hotspot underlying a human genomic disorder

  2012cited by this paper
• Sporadic NF1 mutation associated with a de-novo deletion explains

  2012cited by this paper
• Extending the scope of diagnostic chromosome analysis: Detection of single gene defects using high‐resolution SNP microarrays

  2011cited by this paper
• A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease

  2011cited by this paper
• Motor chip: a comparative genomic hybridization microarray for copy-number mutations in 245 neuromuscular disorders.

  2011cited by this paper
• Copy Number Variation in Familial Parkinson Disease

  2011cited by this paper
• Detection of mosaicism for genome imbalance in a cohort of 3,042 clinical cases using an oligonucleotide array CGH platform.

  2011cited by this paper
• Differential effect of oxidative or excitotoxic stress on the transcriptional profile of amyotrophic lateral sclerosis‐linked mutant SOD1 cultured neurons

  2011cited by this paper
• Comparative genomic hybridization on microarray (a-CGH) in constitutional and acquired mosaicism may detect as low as 8% abnormal cells

  2011cited by this paper
• Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis

  2010cited by this paper
• Mutations in CHMP 2 B in Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis ( ALS )

  2010cited by this paper
• Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.

  2010cited by this paper
• Mutations in CHMP2B in Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis (ALS)

  2010cited by this paper
• Genome-Wide Copy Number Variation in Epilepsy: Novel Susceptibility Loci in Idiopathic Generalized and Focal Epilepsies

  2010cited by this paper
• Detection of clinically relevant exonic copy‐number changes by array CGH

  2010cited by this paper
• Accurate and objective copy number profiling using real-time quantitative PCR.

  2010cited by this paper
• A large genome scan for rare CNVs in amyotrophic lateral sclerosis.

  2010cited by this paper
• R Development Core Team (2010): R: A language and environment for statistical computing

  2010cited by this paper
• Genetic testing in the epilepsies—Report of the ILAE Genetics Commission

  2010cited by this paper
• NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype

  2010cited by this paper
• Targeted comparative genomic hybridization array for the detection of single- and multiexon gene deletions and duplications

  2009influential reference
• Structural Chromosomal Variations in Neurological Diseases

  2009cited by this paper
• CNV and nervous system diseases – what’s new?

  2009cited by this paper
• Technical Advance Detection and Characterization of NF1 Microdeletions by Custom High Resolution Array CGH

  2009cited by this paper
• Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease

  2009cited by this paper
• Detection and characterization of NF1 microdeletions by custom high resolution array CGH.

  2009cited by this paper
• Evaluation of the Golgi trafficking protein VPS54 (wobbler) as a candidate for ALS

  2008cited by this paper
• Segmental neurofibromatosis associated with renal angiomyolipomas.

  2008cited by this paper
• Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States

  2007cited by this paper
• ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B)

  2006cited by this paper
• Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders.

  2006cited by this paper
• Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)

  2005cited by this paper
• Molecular pathophysiology of Parkinson's disease.

  2005cited by this paper
• High-resolution array-CGH profiling of germline and tumor-specific copy number alterations on chromosome 22 in patients affected with schwannomas

  2005cited by this paper
• Comparison of different techniques for detecting 17p12 duplication in CMT1A.

  2005cited by this paper
• Comparative genomic hybridization (CGH)‐arrays pave the way for identification of novel cancer‐related genes

  2004cited by this paper
• Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features

  2004cited by this paper
• Detection of large-scale variation in the human genome

  2004cited by this paper
• A tiling resolution DNA microarray with complete coverage of the human genome

  2004cited by this paper
• Parkin Transcript Variants in Rat and Human Brain

  2004cited by this paper
• Comparative analysis of comparative genomic hybridization microarray technologies: report of a workshop sponsored by the Wellcome Trust.

  2002cited by this paper
• Frontotemporal dementia

  1999cited by this paper
• Spinocerebellar ataxia type 6

  1997cited by this paper

• Increased copy-number variant load of associated risk genes in sporadic cases of amyotrophic lateral sclerosis

  2024influential citation
• OMICS-BASED EXPLORATION AND FUNCTIONAL VALIDATION OF NEUROTROPHIC FACTORS AND HISTAMINE AS THERAPEUTIC TARGETS IN ALS.

  2020cites this paper
• Genomic Portrait of a Sporadic Amyotrophic Lateral Sclerosis Case in a Large Spinocerebellar Ataxia Type 1 Family

  2020cites this paper
• Translational Medicine in Neurological Disorders: A Genomic Perspective

  2019cites this paper