title: Array-based Identification of Copy Number Changes in a Diagnostic Setting: Simultaneous gene-focused and low resolution whole human genome analysis.
abstract: OBJECTIVE
  The aim of this study was to develop and validate a comparative genomic hybridisation (CGH) array that would allow simultaneous targeted analysis of a panel of disease genes and low resolution whole genome analysis.
  
  
  METHODS
  A bespoke Roche NimbleGen 12x135K CGH array (Roche NimbleGen Inc., Madison, Wisconsin, USA) was designed to interrogate the coding regions of 66 genes of interest, with additional widely-spaced backbone probes providing coverage across the whole genome. We analysed genomic deoxyribonucleic acid (DNA) from 20 patients with a range of previously characterised copy number changes and from 8 patients who had not previously undergone any form of dosage analysis.
  
  
  RESULTS
  The custom-designed Roche NimbleGen CGH array was able to detect known copy number changes in all 20 patients. A molecular diagnosis was also made for one of the additional 4 patients with a clinical diagnosis that had not been confirmed by sequence analysis, and carrier testing for familial copy number variants was successfully completed for the remaining four patients.
  
  
  CONCLUSIONS
  The custom-designed CGH array described here is ideally suited for use in a small diagnostic laboratory. The method is robust, accurate, and cost-effective, and offers an ideal alternative to more conventional targeted assays such as multiplex ligation-dependent probe amplification.
authors.affiliation: Diagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland, New Zealand;
authors.forename: Renate
authors.initials: R
authors.lastname: Marquis-Nicholson
authors.forename: Elaine
authors.initials: E
authors.lastname: Doherty
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Love
authors.forename: Chuan-Ching
authors.initials: CC
authors.lastname: Lan
authors.forename: Alice M
authors.initials: AM
authors.lastname: George
authors.forename: Anthony
authors.initials: A
authors.lastname: Thrush
authors.forename: Donald R
authors.initials: DR
authors.lastname: Love
keywords: Array comparative genomic hybridization (aCGH); Copy number variants (CNVs); DNA microarray; Gene dosage; Molecular diagnosis