title: Detection and characterization of the CYP2D6*9x2 gene duplication in two Spanish populations: resolution of AmpliChip CYP450 test no-calls.
abstract: BACKGROUND
  CYP2D6 is a major drug-metabolizing enzyme. Polymorphic variation includes copy number variants such as gene deletions, duplications and multiplications of functional and nonfunctional gene units. In this article we describe the first systematic characterization of a CYP2D6*9x2 gene duplication. CYP2D6*9 is an allelic variant conferring reduced enzymatic activity. This novel gene duplication was discovered in two unrelated Spanish psychiatric patients. Both subjects were initially tested with the AmpliChip CYP450 test, which indicated the presence of a duplication and the CYP2D6*9 allele, but did not make a genotype call. The goal of the study was to resolve this issue by characterizing the CYP2D6 gene locus in these patients.
  
  
  METHODS
  Both individuals and one offspring were regenotyped using our own CYP2D6 genotyping strategy employing long-range PCR and TaqMan-based SNP detection. In addition, gene resequencing and genotyping of duplication-specific long-range PCR products and quantitative gene copy number analysis was applied.
  
  
  RESULTS
  The duplication was mapped to the CYP2D6*9 allele and copy number analysis determined a CYP2D6*9x2 gene duplication in all three individuals. Because CYP2D6*9x2 is not recognized by the AmpliChip CYP450 test, this structural arrangement was responsible for the 'no call' on the AmpliChip CYP450 test report.
  
  
  CONCLUSIONS
  The full characterization of this allele will aid in the interpretation of AmpliChip CYP450 test results for clinical and research applications. Original submitted 8 June 2011; Revision submitted 18 July 2011.
authors: Laboratori de Referencia de Catalunya, El Prat de Llobregat, Barcelona, Spain. agaedigk@cmh.edu
authors: Andrea
authors: A
authors: Gaedigk
authors: Juanjo
authors: J
authors: Hernandez
authors: Virginia
authors: V
authors: García-Solaesa
authors: Santiago
authors: S
authors: Sánchez
authors: Maria
authors: M
authors: Isidoro-García
mesh_terms: D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics*; D020440:Gene Duplication; D005787:Gene Frequency / Q000235:genetics; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011153:Population / Q000235:genetics*; D013030:Spain
chemical_list: D019389:Cytochrome P-450 CYP2D6