High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping

作者：Daniel A. Peiffer, Jennie M. Le, Frank J. Steemers, Weihua Chang, Tony Jenniges, Francisco Garcia‐García, Kirt Haden, Jiangzhen Li, Chad A. Shaw, John W. Belmont, Sau Wai Cheung, Richard Shen, David L. A. Barker, Kevin L. Gunderson · 发表于：Genome Research · 年份：2006 · DOI：10.1101/gr.5402306 · 被引用次数：542 · 研究领域：Genomic variations and chromosomal abnormalities、Cancer Genomics and Diagnostics、Genomics and Chromatin Dynamics

Array-CGH is a powerful tool for the detection of chromosomal aberrations. The introduction of high-density SNP genotyping technology to genomic profiling, termed SNP-CGH, represents a further advance, since simultaneous measurement of both signal intensity variations and changes in allelic composition makes it possible to detect both copy number changes and copy-neutral loss-of-heterozygosity (LOH) events. We demonstrate the utility of SNP-CGH with two Infinium whole-genome genotyping BeadChips, assaying 109,000 and 317,000 SNP loci, to detect chromosomal aberrations in samples bearing constitutional aberrations as well tumor samples at sub-100 kb effective resolution. Detected aberrations include homozygous deletions, hemizygous deletions, copy-neutral LOH, duplications, and amplifications. The statistical ability to detect common aberrations was modeled by analysis of an X chromosome titration model system, and sensitivity was modeled by titration of gDNA from a tumor cell with that of its paired normal cell line. Analysis was facilitated by using a genome browser that plots log ratios of normalized intensities and allelic ratios along the chromosomes. We developed two modes of SNP-CGH analysis, a single sample and a paired sample mode. The single sample mode computes log intensity ratios and allelic ratios by referencing to canonical genotype clusters generated from approximately 120 reference samples, whereas the paired sample mode uses a paired normal reference sample f...