title: Multiallelic synthetic quality control material: lessons learned from the cystic fibrosis external quality assessment scheme.
abstract: OBJECTIVE
  With the arrival of increasingly complex molecular tests, we are obliged to create new ways to monitor and troubleshoot the underperformance of these multiplex assays. A synthetic multiallelic quality control material has been designed to augment genomic DNA controls. We aimed to evaluate the control on a large scale, testing it on a wide variety of oligonucleotide ligation assays, test protocols, and analysis software. In addition, we investigated how laboratories treat untried and complex materials.
  
  
  METHODS
  The synthetic control monitored 32 cystic fibrosis transmembrane conductance regulator mutations and polymorphisms simultaneously. Participants of a cystic fibrosis external quality assessment scheme were invited to analyze the quality control.
  
  
  RESULTS
  In total, 58 laboratories participated in this study. Twenty-seven (47%) laboratories detected 32 variants; another 27 laboratories (47%) detected from 31 to 4 variants and 4 participants reported no variants (6%). The main observations included administrative errors when indicating variants on a checklist, errors caused by misreading the instructions for use of the control or assay, and technical problems related to the assay used.
  
  
  CONCLUSIONS
  Synthetic quality control materials proved to be valuable in troubleshooting underperforming assays and complement existing genomic controls. The study also revealed a strong need for increased quality control in the postanalytical phase of testing.
authors.affiliation: Biomedical Quality Assurance Research Unit, Department of Human Genetics, University of Leuven, Leuven, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Berwouts
authors.forename: Todd M
authors.initials: TM
authors.lastname: Christensen
authors.forename: Jill
authors.initials: J
authors.lastname: Brandon
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Bejjani
authors.forename: David E
authors.initials: DE
authors.lastname: Barton
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dequeker
mesh_terms: D000483:Alleles; D002138:Calibration; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005813:Genes, Synthetic / Q000502:physiology; D005820:Genetic Testing; D005843:Geography; D059014:High-Throughput Nucleotide Sequencing / Q000592:standards*; D006801:Humans; D007753:Laboratories / Q000592:standards; D007858:Learning; D060885:Multiplex Polymerase Chain Reaction / Q000592:standards*; D011786:Quality Control; D012015:Reference Standards; D012107:Research Design
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator