Tips for CNV Detection

Related Articles How It Works: CGH Arrays Genomic Alterations 2.0 Bac in time Aneuploid problems Old dog, new tricks Multiplex for control Needle in the haystack Keep it clean - Do everything you can to remove proteins and keep the DNA from degrading, Scherer says. "Sample preparation is critical. All problems, in some way, can be tracked back to the quality of the DNA." Double up - If your lab can afford it, run samples with two types of arrays. Lo was able to confir

Melissa Lee Phillips
Oct 1, 2007

Keep it clean - Do everything you can to remove proteins and keep the DNA from degrading, Scherer says. "Sample preparation is critical. All problems, in some way, can be tracked back to the quality of the DNA."

Double up - If your lab can afford it, run samples with two types of arrays. Lo was able to confirm some dodgy-looking BAC findings with higher-density arrays, he says. SNP arrays can provide good backup to oligonucleotide arrays, and for any genetic studies, notes Scherer, "having both the SNP info and the CNV info is really advantageous." If two platforms are out of your price range, consider SNP arrays to detect both SNPs and CNVs. Be wary, however, of their whole-genome amplifications of starting DNA,...

CNV DETECTION PLATFORMS

PlatformCostProsCons
CGH Arrays
Bacterial Artificial Chromosome arrays ~$500 per array
(300 unique clones)
No specialized platform required
• Comprehensive genome coverage
• Robust data with little noise
• Good at capturing larger, more complex CNVs
• Can't reliably identify single copy number differences smaller than ~50kb
• Data not always reproducible
Agilent CGH microarray
www.agilent.com
~$700 per assay
(244,000 features)

~$160,000 (platform)
• Genome coverage so dense that you can essentially resequence areas of interest
• Good for novel or rare CNV detection
• Poor signal-to-noise ratio
NimbleGen NimblChip CGH array
www.nimblegen.com
~$950 per assay *

(2.1 million features)
~$100,000 (platform)*
SNP Genotyping Arrays
Affymetrix 250K Array and SNP Array 6.0
www.affymetrix.com
~$180 per assay
(250,000 features)
~$375 per assay
(1.8 million features)

~200,000 (platform)
• Good for fine-scale copy-number changes
• Can detect both CNVs and SNPs
• Good for matching known CNVs with specific phenotypes
• Uneven distribution of markers means variable resolution across genome
• Probes likely to be sparse in CNV-rich regions
Illumina Human CNV370-Duo BeadChip
www.illumina.com
~$220-280 per assay
(370,000 features)

~$300,000 (platform)
*Company declined to provide pricing info, figures listed are based on a user estimate

Further reading:

S.W. Scherer et al., "Challenges and standards in integrating surveys of structural variation," Nat Genet, 39:S7-S15, 2007. N.P. Carter, "Methods and strategies for analyzing copy number variation using DNA microarrays," Nat Genet, 39:S16-S21, 2007.