title: Development and validation of a CGH microarray for clinical cytogenetic diagnosis.
abstract: OBJECTIVE
  We developed a microarray for clinical diagnosis of chromosomal disorders using large insert genomic DNA clones as targets for comparative genomic hybridization (CGH).
  
  
  METHODS
  The array contains 362 FISH-verified clones that span genomic regions implicated in over 40 known human genomic disorders and representative subtelomeric clones for each of the 41 clinically relevant human chromosome telomeres. Three or four clones from almost all deletion or duplication genomic regions and three or more clones for each subtelomeric region were included. We tested chromosome microarray analysis (CMA) in a masked fashion by examining genomic DNA from 25 patients who were previously ascertained in a genetic clinic and studied by conventional cytogenetics. A novel software package implemented in the R statistical programming language was developed for normalization, visualization, and inference.
  
  
  RESULTS
  The CMA results were entirely consistent with previous cytogenetic and FISH findings. For clone by clone analysis, the sensitivity was estimated to be 96.7% and the specificity was 99.1%. Major advantages of this selected human genome array include the following: interrogation of clinically relevant genomic regions, the ability to test for a wide range of duplication and deletion syndromes in a single analysis, the ability to detect duplications that would likely be undetected by metaphase FISH, and ease of confirmation of suspected genomic changes by conventional FISH testing currently available in the cytogenetics laboratory.
  
  
  CONCLUSIONS
  The array is an attractive alternative to telomere FISH and locus-specific FISH, but it does not include uniform coverage across the arms of each chromosome and is not intended to substitute for a standard karyotype. Limitations of CMA include the inability to detect both balanced chromosome changes and low levels of mosaicism.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors: Sau W
authors: SW
authors: Cheung
authors: Chad A
authors: CA
authors: Shaw
authors: Wei
authors: W
authors: Yu
authors: Jiangzham
authors: J
authors: Li
authors: Zhishuo
authors: Z
authors: Ou
authors: Ankita
authors: A
authors: Patel
authors: Svetlana A
authors: SA
authors: Yatsenko
authors: Mitchell L
authors: ML
authors: Cooper
authors: Patti
authors: P
authors: Furman
authors: Pawel
authors: P
authors: Stankiewicz
authors: Pawal
authors: P
authors: Stankiewicz
authors: James R
authors: JR
authors: Lupski
authors: A Craig
authors: AC
authors: Chinault
authors: Arthur L
authors: AL
authors: Beaudet
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D020732:Cytogenetic Analysis / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D046228:Microarray Analysis; D009693:Nucleic Acid Hybridization / Q000379:methods*; D012680:Sensitivity and Specificity; D016615:Telomere / Q000235:genetics*