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PMID: 16899659 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

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

Genome research ·Vol. 16 ·No. 9 ·2006-09-00 ·Pages 1136-48

Peiffer DA, Le JM, Steemers FJ, Chang W, Jenniges T, Garcia F, Haden K, Li J, Shaw CA, Belmont J, Cheung SW, Shen RM, Barker DL, Gunderson KL

Abstract

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 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.

MeSH Terms
Cell Line, Tumor Chromosome Aberrations Chromosomes, Human/metabolism DNA/metabolism Female Genome, Human Genomics/methods Genotype Humans In Situ Hybridization, Fluorescence Loss of Heterozygosity Male Oligonucleotide Array Sequence Analysis/methods Polymorphism, Single Nucleotide
Chemicals
DNA
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Peiffer Daniel A
Illumina, Inc., San Diego, California 92121, USA.
Le Jennie M
Steemers Frank J
Chang Weihua
Jenniges Tony
Garcia Francisco
Haden Kirt
Li Jiangzhen
Shaw Chad A
Belmont John
Cheung Sau Wai
Shen Richard M
Barker David L
Gunderson Kevin L
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.5402306
Published
2006-09-00
Epub
2006-00-09
Pages
1136-48
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC1557768
Subset
IM
Grants
NCI NIH HHS · R44 CA103406 · United States
NCI NIH HHS · 2 R44 CA103406-02 · United States
External Links
PubMed source DOI: 10.1101/gr.5402306 PMC Full Text View journal details
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