LOH/DNA Copy Number Variation
The ability to simultaneously collect information on both DNA copy number and allelic composition is critical to the understanding of the nature of genomic variation. The Illumina Infinium™ whole-genome assays permit high resolution profiling for both loss of heterozygosity (LOH) and DNA copy number changes. This technology can be used to screen for amplifications, duplications, deletions, and LOH.
Historically, LOH studies helped identify many tumor suppressor genes including RB1 and WT1. In addition to detection of chromosome deletions, LOH analysis also permits identification of copy-neutral genetic abnormalities such as uniparental disomy (UPD) and mitotic recombination.
Recently, hundreds of submicroscopic copy number variants (CNVs) have been described in the human genome. CNVs are a major contributor to genomic variation and have been linked to many genetic disorders due to dosage changes in coding and regulatory regions. Thus, the ability to detect DNA copy number changes has become a vital part of cancer biology studies and the identification of chromosomal imbalances associated with some congenital disorders.
LOH and copy number aberrations are detected by comparing the normalized intensity of a subject sample to a reference sample using two methods of analysis. In the first method, the subject sample is compared to ~120 normal HapMap reference samples. The second method uses a paired-sample analysis in which there is a direct intensity (R) comparison between a subject sample and its corresponding matched pair. Chromosomal aberrations are accurately identified by use of KaroyStudio software.
Infinium Whole-Genome Genotyping BeadChips for LOH and CNV Studies
Human660W Quad BeadChip: PDF
An ideal combination of high-coverage genome-wide SNP and CNV markers in a high-throughput format, this BeadChip builds on the content of the HumanHap 550 BeadChip. For powerful CNV and cytogenetic analysis, included are an additional approximately 100,000 markers developed in collaboration with researchers around the world that target observed common CNVs based on HapMap data.
HumanOmni 1-Quad BeadChip: PDF
Genome-wide coverage from the 1,000 Genomes Project and confirmed disease associations. High marker density and the fewest large gaps ensure precise CNV detection - more than 6,000 common and 5,000 rare CNV regions with 10–15 markers per region. The HumanOmni1-Quad BeadChip’s high-throughput format and low sample input requirements (200 ng) support rapid, cost-effective studies.
Human 1M Duo BeadChip: PDF
This BeadChip has an unprecedented level of coverage for SNP and non-SNP loci and provides uniform spacing for analysis of both known and novel DNA CNVs with high density coverage for greater than 99% of known genes. The CNV regions represented on this BeadChip include unstable portions of the genome such as segmental duplication, megasatellites, SNP deserts, and the MHC region. It covers most of the CNVs published in the Database of Genomic Variants (DGV) as well as novel CNVs not found in the DGV.
HumanCytoSNP-12 BeadChip: PDF
A 12-sample BeadChip featuring approximately 300,000 genetic markers that target abnormalities associated with more than 300 syndromes containing 200,000 informative tag SNPs. This BeadChip can quickly and cost effectively screen for single-nucleotide polymorphisms associated with diseases, analyze structural variation, and identify copy-neutral LOH events such as uniparental disomy, which are undetectable on current array-CGH products.
CNVs and GWAS (Genome-Wide Association Studies)
Some of the most promising work to emerge this year has been associating copy number variants (CNVs) with disease. More and more studies show that CNVs are involved in diseases as varied as cancer, macular degeneration, obesity, and others. High-density SNP and CNV chips are moving scientists not only into genome-wide CNV analysis, but also to performing CNV association studies to learn how previously undetectable CNVs might contribute to disease susceptibility.
The lllumina Infinium HD Human 660W-Quad BeadChip features 2.6 million genetic markers and targets more than 5,000 CNV regions in the human genome. The chip covers all the known common CNVs, so it could be used to screen for variants and to perform GWAS. The idea is to incorporate these into association studies to see if they actually do lend susceptibility to various diseases.
To get the most comprehensive amount of information for genetic variation, run the SNP array and CNV array, and then combine the data. For researchers performing whole-genome SNP and CNV studies, the upcoming Illumina HumanOmni1-Quad BeadChip provides the fastest and most cost-efficient tool for finding meaningful disease-associations. With over four million data points on a single BeadChip, this array includes up-to-date content for all major classes of genetic variation for the study of human disease. The BeadChip utilizes tag SNPs from all three phases of the International HapMap Project and offers premier coverage of known regions of CNV and SNPs of known disease association. In addition, the HumanOmni1-Quad BeadChip is the first commercially-available product to offer content derived from the 1,000 Genomes Project.