title: An experimental loop design for the detection of constitutional chromosomal aberrations by array CGH.
abstract: BACKGROUND
  Comparative genomic hybridization microarrays for the detection of constitutional chromosomal aberrations is the application of microarray technology coming fastest into routine clinical application. Through genotype-phenotype association, it is also an important technique towards the discovery of disease causing genes and genomewide functional annotation in human. When using a two-channel microarray of genomic DNA probes for array CGH, the basic setup consists in hybridizing a patient against a normal reference sample. Two major disadvantages of this setup are (1) the use of half of the resources to measure a (little informative) reference sample and (2) the possibility that deviating signals are caused by benign copy number variation in the "normal" reference instead of a patient aberration. Instead, we apply an experimental loop design that compares three patients in three hybridizations.
  
  
  RESULTS
  We develop and compare two statistical methods (linear models of log ratios and mixed models of absolute measurements). In an analysis of 27 patients seen at our genetics center, we observed that the linear models of the log ratios are advantageous over the mixed models of the absolute intensities.
  
  
  CONCLUSIONS
  The loop design and the performance of the statistical analysis contribute to the quick adoption of array CGH as a routine diagnostic tool. They lower the detection limit of mosaicisms and improve the assignment of copy number variation for genetic association studies.
authors.affiliation: MicroArray Facility, VIB, Leuven, Belgium. joke.allemeersch@vib.be
authors.forename: Joke
authors.initials: J
authors.lastname: Allemeersch
authors.forename: Steven
authors.initials: S
authors.lastname: Van Vooren
authors.forename: Femke
authors.initials: F
authors.lastname: Hannes
authors.forename: Bart
authors.initials: B
authors.lastname: De Moor
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Yves
authors.initials: Y
authors.lastname: Moreau
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization / Q000379:methods*; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D056726:Genetic Association Studies; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D012107:Research Design / Q000592:standards*