Reliable Detection of Copy Number Changes

Whether you're studying somatic events in tumor samples or germline changes in children with congenital disease, GeneChip® SNP arrays provide the coverage and sensitivity required to identify gross and small chromosomal abnormalities in your samples.

The Genome-Wide Human SNP Array 6.0 provides copy number estimates for more than 1.8 million markers on a single array, more than half of which are non-polymorphic probes selected for their linear response to copy number and genomic position. These two attributes provide a combination of high copy number performance and even distribution across the genome. With an inter-marker distance of 696 base pairs, even very small gains and losses are predicted by a large number of data points. This means increased confidence in the presence of a copy number change and the fine-mapping of breakpoints.

Copy number probes were empirically selected based on dose response to DNA copy number (See Figure 1).

Loss of Heterozygosity and Uniparental Disomy

Copy number changes aren't the only genomic alterations with important implications for disease. Loss of heterozygosity (LOH) can occur with or without copy number change (Figure 2) and also influences downstream cellular functions with pathogenic effects. LOH may result in the loss of a wild-type allele and exposure to the mutated form of a gene or transfer of the mutated allele to both homologs (through apparent mitotic recombination) or may be due to the inheritance of two post meiotic homologs from the same parent (uniparental disomy or UPD). The first example of copy-neutral LOH and UPD 7 identified in humans resulted in two copies of a mutation in CFTR, leading to cystic fibrosis and an imprinting syndrome. In tumors, regions of LOH frequently indicate the presence of an altered tumor suppressor gene. LOH can also influence disease progression by altering a region affected by imprinting, as commonly seen in Wilms' Tumor.

The SNP Array 6.0 interrogates more than 900,000 SNPs, all of which can be used to identify homozygous stretches of DNA that were either acquired somatically or inherited in Mendelian or non-Mendelian fashion. The combination of copy number with LOH means that regions of copy-neutral LOH (also known as uniparental disomy, or UPD) can easily be identified. These events, extremely important in both cancer samples and general cytogenetic cases, cannot be detected using traditional cytogenetic methods or comparative genomic hybridization (CGH). Yet ignoring regions of LOH in any of these cases means looking only at a partial picture of the disease genome.

Application Note: Copy-neutral Loss of Heterozygosity in Cancer (pdf, 1.07 MB)

Affymetrix-recommended Solutions for Copy Number and Loss of Heterozygosity

Affymetrix provides targeted solutions to meet the needs of the cytogeneticist and cancer researcher.

Recommended solutions for cytogenetic analysis of germline changes include:

• The NEW Cytogenetics Copy Number Assay for a simple workflow and flexible throughput
• The SNP Array 6.0 for extensive coverage, including subtelomeres, pericentromeres and the Y chromosome
• The Affymetrix® Genome-Wide Human SNP Nsp/Sty Assay Kit 5.0/6.0 (30 reactions) for robust processing of samples
• Genotyping Console software for an easy-to-use tool with whole-genome karyoviews (Figure 3), chromosome views aligning copy number and LOH with annotated genes and CNVs, and a summarization of all detected gains and losses

Recommended solutions for cancer research of somatic changes in tumors include:

• The NEW Cytogenetics Copy Number Assay for a simple workflow and flexible throughput
• The SNP Array 6.0 for the highest coverage combining whole-genome copy number and LOH detection on a single array
• The Affymetrix® Genome-Wide Human SNP Nsp/Sty Assay Kit 5.0/6.0 (30 reactions) for robust processing of samples
• Partek® Genomics Suite™ software for identification of chromosomal aberrations, filtering for recurring gains, losses or LOH across samples, clustering, integrating with expression or ChIP-on-chip data, correlations and more

GeneChip® SNP arrays are for research use only and are not for use in diagnostic procedures.

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Genome-Wide SNP Array 6.0 for Copy Number and Loss of Heterozygosity

With the Genome-Wide SNP Array 6.0, you can identify small and large copy number changes and identify the breakpoints so you'll know which genes or exons are within the chromosomal aberrations. By combining SNP genotype with copy number detection, you can also identify LOH with or without copy number changes, such as regions of uniparental disomy (UPD). The SNP Array 6.0 provides the solution with the highest coverage for combined copy number and LOH detection, so you can detect important aberrations in your samples. For more information, see our brochure The Affymetrix® Solution for Molecular Cytogenetics.

The Affymetrix® Genome-Wide Human SNP Nsp/Sty Assay Kit 5.0/6.0

The Genome-Wide Human SNP Nsp/Sty Assay Kit 5.0/6.0 provides flexibility in throughput for cytogenetics and cancer studies. Use the 30 reaction kit for the Cytogenetics Copy Number Assay, designed for runs of four to 24 samples at a time. With robust performance, this assay has consistently provided high-quality results across samples and across sites trained on the three- or four-day protocol.

Genotyping Console for Cytogenetics

Genotyping Console performs copy number and LOH analysis using SNP Array 6.0 data. Gains and losses are summarized by the Segment Reporting Tool and displayed in the new Genotyping Console Browser. This browser allows you to migrate from high-level, whole-genome views to detailed visualizations of copy number changes as they are aligned to annotated genes and CNVs, FISH clones or customized tracks. Download Cytogenetics Demo Data (zip, 338 MB).

GeneChip-compatible™ Software for Cancer Research

For a full-featured solution for copy number analysis in cancer studies, we recommend Partek® Genomics Suite™.

GeneChip® SNP arrays are for research use only and are not for use in diagnostic procedures.

Using Affymetrix' SNP Array 6.0 for Copy Number Research in Cancer with Partek's Genomics Suite

Tom Downey, President and Data Analysis Consultant at Partek®, Inc.

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