title: Density matters: comparison of array platforms for detection of copy-number variation and copy-neutral abnormalities.
abstract: OBJECTIVE
  A combination of oligonucleotide and single-nucleotide polymorphism probes on the same array platform can detect copy-number abnormalities and copy-neutral aberrations such as uniparental disomy and long stretches of homozygosity. The single-nucleotide polymorphism probe density in commercially available platforms varies widely, which may affect the detection of copy-neutral abnormalities.
  
  
  METHODS
  We evaluated the ability of array platforms with low (Oxford Gene Technology CytoSure ISCA uniparental disomy), mid-range (Agilent custom array), and high (Affymetrix CytoScan HD) single-nucleotide polymorphism probe density to detect copy-number variation, mosaicism, uniparental isodisomy, and absence of heterozygosity in 50 clinical samples.
  
  
  RESULTS
  All platforms reliably detected copy-number variation, mosaicism, and uniparental isodisomy; however, absence-of-heterozygosity detection varied significantly. The low-density array called absence-of-heterozygosity regions not confirmed by the other platforms and also overestimated the length of true absence-of-heterozygosity regions. Furthermore, the low- and mid-density platforms failed to detect some small absence-of-heterozygosity regions that were identified by the high-density platform.
  
  
  CONCLUSIONS
  Variation in single-nucleotide polymorphism density can lead to major discrepancies in the detection of and confidence in copy-neutral abnormalities. Although suitable for uniparental disomy detection, copy-number plus single-nucleotide polymorphism arrays with 30,000 or fewer unique single-nucleotide polymorphism probes miscall absence-of-heterozygosity regions due to identity by descent.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Mason-Suares
authors.forename: Wayne
authors.initials: W
authors.lastname: Kim
authors.forename: Leslie
authors.initials: L
authors.lastname: Grimmett
authors.forename: Eli S
authors.initials: ES
authors.lastname: Williams
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Horner
authors.forename: Dawn
authors.initials: D
authors.lastname: Kunig
authors.forename: Ian S
authors.initials: IS
authors.lastname: Goldlust
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Wu
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
authors.forename: Christa L
authors.initials: CL
authors.lastname: Martin
authors.forename: M Katharine
authors.initials: MK
authors.lastname: Rudd
mesh_terms: D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods*; D003241:Consanguinity; D056915:DNA Copy Number Variations; D015342:DNA Probes; D005260:Female; D015894:Genome, Human; D064368:Healthy Volunteers; D006720:Homozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy / Q000235:genetics
chemical_list: D015342:DNA Probes