Density matters: comparison of array platforms for detection of copy-number variation and copy-neutral abnormalities.

Abstract

PURPOSE:

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.

CONCLUSION:

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: Heather Mason-Suares, Wayne Kim, Leslie Grimmett, Eli S Williams, Vanessa L Horner, Dawn Kunig, Ian S Goldlust, Bai-Lin Wu, Yiping Shen, David T Miller, Christa L Martin, M Katharine Rudd
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 15 Issue 9 Pg. 706-12 (Sep 2013) ISSN: 1530-0366 [Electronic] United States
• PMID: 23558256 (Publication Type: Comparative Study, Evaluation Study, Journal Article)

Chemical References

• DNA Probes

Topics

• Chromosome Aberrations
• Comparative Genomic Hybridization (methods)
• Consanguinity
• DNA Copy Number Variations
• DNA Probes
• Female
• Genome, Human
• Healthy Volunteers
• Homozygote
• Humans
• Loss of Heterozygosity
• Male
• Oligonucleotide Array Sequence Analysis (methods)
• Polymorphism, Single Nucleotide
• Uniparental Disomy (genetics)