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 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 determined by genomic plots of the log2 (Rsubject/Rreference; Log R ratio), CNV analysis plug-inand the allelic frequencies.
Infinium Whole-Genome Genotyping BeadChips for LOH and CNV Studies
HumanHap300 and HumanHap300-Duo:
This BeadChip contains over 317,000 SNPs with a median spacing of ~5kb. The array detects 85.2% of the ~1700 CNV regions in the Database of Genomic Variants. The HumanHap 300 Duo BeadChip is a two sample format to allow a direct comparison between a subject and reference sample.
Human CNV370-Duo:
This BeadChip contains the content available on the HumanHap 300-Duo plus an additional ~55,000 markers specifically designed to target nearly 11,000 copy number variant regions of the genome. Included are probes for SNP and non-SNP sites. The CNV regions covered on this BeadChip include those unstable portions of the genome such as segmental duplication, megasatellites, SNP deserts, and the MHC region. The majority (85%) of the CNV regions targeted are between 1 to 10 kb which are currently underrepresented in public databases.
HumanHap550 and HumanMap550-Duo:
This BeadChip contains over 550,000 SNP loci with a median spacing of ~2.8kb. The array detects 93.7% of the ~1700 CNV regions in the Database of Genomic Variants. The HumanMap550-Duo allows two samples to be processed simultaneously on a single BeadChip.
Human650Y:
This BeadChip contains over 650,000 SNP loci including additional SNP content for the Yoruba population. The median spacing is ~2.0kb and the array detects 94.3% of the ~1700 CNV regions in the Database of Genomic Variants.
Human 1 M:
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 copy number variants (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.