title: UGT2B17 and SULT1A1 gene copy number variation (CNV) detection by LabChip microfluidic technology.
abstract: BACKGROUND
  Gene copy number variations (CNVs) are increasingly recognized to play important roles in the expression of genes and hence on their respective enzymatic activities. This has been demonstrated for a number of drug metabolizing genes, such as UDP-glucuronosyltransferases 2B17 (UGT2B17) and sulfotransferase 1A1 (SULT1A1), which are subject to genetic heterogeneity, including CNV. Quantitative assays to assess gene copy number are therefore becoming an integral part of accurate genotype assessment and phenotype prediction.
  
  
  METHODS
  In this study, we evaluated a microfluidics-based system, the Bio-Rad Experion system, to determine the power and utility of this platform to detect UGT2B17 and SULT1A1 CNV in DNA samples derived from blood and tissue. UGT2B17 is known to present with 0, 1 or 2 and SULT1A1 with up to 5 gene copies.
  
  
  RESULTS
  Distinct clustering (p<0.001) into copy number groups was achieved for both genes. DNA samples derived from blood exhibited less inter-run variability compared to DNA samples obtained from liver tissue. This variability may be caused by tissue-specific PCR inhibitors as it could be overcome by using DNA from another tissue, or after the DNA had undergone whole genome amplification.
  
  
  CONCLUSIONS
  This method produced results comparable to those reported for other quantitative test platforms.
authors.affiliation: Section of Developmental Pharmacology and Experimental Therapeutics, The Children's Mercy Hospital and Clinics, Kansas City, MO 64108 , USA. agaedigk@cmh.edu
authors.forename: Andrea
authors.initials: A
authors.lastname: Gaedigk
authors.forename: Roger
authors.initials: R
authors.lastname: Gaedigk
authors.forename: J Steven
authors.initials: JS
authors.lastname: Leeder
mesh_terms: D015239:Arylsulfotransferase / Q000235:genetics*; D016000:Cluster Analysis; D018628:Gene Dosage; D005787:Gene Frequency; D015894:Genome, Human; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide
chemical_list: D015778:Minor Histocompatibility Antigens; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human