title: Comparison of genome-wide array genomic hybridization platforms for the detection of copy number variants in idiopathic mental retardation.
abstract: BACKGROUND
  Clinical laboratories are adopting array genomic hybridization as a standard clinical test. A number of whole genome array genomic hybridization platforms are available, but little is known about their comparative performance in a clinical context.
  
  
  METHODS
  We studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500 K GeneChip SNP arrays, Agilent Human Genome 244 K oligonucleotide arrays and NimbleGen 385 K Whole-Genome oligonucleotide arrays. We also determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32 K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP arrays.
  
  
  RESULTS
  The Affymetrix 500 K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosomal CNVs in the 30 trios. 147 of these CNVs appeared to be de novo, but only 34 (22%) were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 most likely pathogenic and 2 possibly pathogenic CNVs for MR. All 9 of these putatively pathogenic CNVs were detected by the Affymetrix 500 K, Agilent, NimbleGen and the Illumina arrays, and 5 were found by the SMRT BAC array. Both putatively pathogenic CNVs identified in the 15 trios tested with the Affymetrix 6.0 were identified by this platform.
  
  
  CONCLUSIONS
  Our findings demonstrate that different results are obtained with different platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls on each of the platforms supports the need for validating clinically important findings with a different technology.
authors: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. tbtucker@interchange.ubc.ca
authors: Tracy
authors: T
authors: Tucker
authors: Alexandre
authors: A
authors: Montpetit
authors: David
authors: D
authors: Chai
authors: Susanna
authors: S
authors: Chan
authors: Sébastien
authors: S
authors: Chénier
authors: Bradley P
authors: BP
authors: Coe
authors: Allen
authors: A
authors: Delaney
authors: Patrice
authors: P
authors: Eydoux
authors: Wan L
authors: WL
authors: Lam
authors: Sylvie
authors: S
authors: Langlois
authors: Emmanuelle
authors: E
authors: Lemyre
authors: Marco
authors: M
authors: Marra
authors: Hong
authors: H
authors: Qian
authors: Guy A
authors: GA
authors: Rouleau
authors: David
authors: D
authors: Vincent
authors: Jacques L
authors: JL
authors: Michaud
authors: Jan M
authors: JM
authors: Friedman
mesh_terms: D002648:Child; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization / Q000379:methods*; D018628:Gene Dosage / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011933:Reagent Kits, Diagnostic
chemical_list: D011933:Reagent Kits, Diagnostic