TY  - JOUR
A1  - Peiffer, Daniel A.
A1  - Le, Jennie M.
A1  - Steemers, Frank J.
A1  - Chang, Weihua
A1  - Jenniges, Tony
A1  - Garcia, Francisco
A1  - Haden, Kirt
A1  - Li, Jiangzhen
A1  - Shaw, Chad A.
A1  - Belmont, John
A1  - Cheung, Sau Wai
A1  - Shen, Richard M.
A1  - Barker, David L.
A1  - Gunderson, Kevin L.
T1  - High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping
Y1  - 2006/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1136 
EP  - 1148 
DO  - 10.1101/gr.5402306 
VL  - 16 
IS  - 9 
UR  - http://genome.cshlp.org/content/16/9/1136.abstract 
N2  - 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 ∼120 reference samples, whereas the paired sample mode uses a paired normal reference sample from the same individual. Finally, the two analysis modes are compared and contrasted for their utility in analyzing different types of input gDNA: low input amounts, fragmented gDNA, and Phi29 whole-genome pre-amplified DNA. 
ER  -