title: Analysis of gene copy number variations using  a method based on lab-on-a-chip technology.
abstract: OBJECTIVE
  Copy number variations (CNVs) contribute to genome variability and their pathogenic role is becoming evident in an increasing number of human disorders. Commercial assays for routine diagnosis of CNVs are available only for a fraction of known genomic rearrangements. Thus, it is important to develop flexible and cost-effective methods that can be adapted to the detection of CNVs of interest, both in research and clinical settings.
  
  
  METHODS
  We describe a new multiplex PCR-based method for CNV analysis that exploits automated microfluidic capillary electrophoresis through lab-on-a-chip technology (LOC-CNV). We tested the reproducibility of the method and compared the results obtained by LOC-CNV with those obtained using previously validated semiquantitative assays such as multiplex ligation-dependent probe amplification (MLPA) and nonfluorescent multiplex PCR coupled to HPLC (NFMP-HPLC).
  
  
  RESULTS
  The results obtained by LOC-CNV in control individuals and carriers of pathogenic MLH1 or BRCA1 genomic rearrangements (losses or gains) were concordant with those obtained by previously validated methods, indicating that LOC-CNV is a reliable method for the detection of genomic rearrangements.
  
  
  CONCLUSIONS
  Because of its advantages with respect to time, costs, easy adaptation of previously developed multiplex assays and flexibility in novel assay design, LOC-CNV may represent a practical option to evaluate relative copy number changes in genomic targets of interest, including those identified in genome-wide analyses.
authors.affiliation: Department of Drug Sciences, G. d’Annunzio University, Chieti, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Lellis
authors.forename: Sandra
authors.initials: S
authors.lastname: Mammarella
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Curia
authors.forename: Serena
authors.initials: S
authors.lastname: Veschi
authors.forename: Zhirajr
authors.initials: Z
authors.lastname: Mokini
authors.forename: Chiara
authors.initials: C
authors.lastname: Bassi
authors.forename: Paola
authors.initials: P
authors.lastname: Sala
authors.forename: Pasquale
authors.initials: P
authors.lastname: Battista
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D056915:DNA Copy Number Variations; D005060:Europe; D015321:Gene Rearrangement; D006579:Heterozygote; D006801:Humans; D056656:Lab-On-A-Chip Devices / Q000191:economics / Q000706:statistics & numerical data; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1