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Published online 17 May 2004

Nucleic Acids Research, 2004, Vol. 32, No. 9 e69
© 2004 Oxford University Press

Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA

Kwong-Kwok Wong*, Yvonne T. M. Tsang, Jianhe Shen, Rita S. Cheng, Yi-Mieng Chang, Tsz-Kwong Man and Ching C. Lau*

Texas Children’s Cancer Center, Cancer Genomics Group, MC3-3320, Department of Pediatrics, Baylor College of Medicine, 6621 Fannin Street, Houston, TX 77030, USA

*To whom correspondence should be addressed. Tel: +1 832 824 4373; Fax: +1 832 825 4038; Email: kkwong{at}bcm.tmc.edu
Correspondence may also be addressed to Ching C. Lau. Tel: +1 832 824 4543; Fax: +1 832 825 4038; Email: cclau{at}txccc.org

Received March 19, 2004; Revised and Accepted April 22, 2004

Besides their use in mRNA expression profiling, oligonucleotide microarrays have also been applied to single-nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) or allelic imbalance studies. In this report, we evaluate the reliability of using whole genome amplified DNA for analysis with an oligonucleotide microarray containing 11 560 SNPs to detect allelic imbalance and chromosomal copy number abnormalities. Whole genome SNP analyses were performed with DNA extracted from osteosarcoma tissues and patient-matched blood. SNP calls were then generated by Affymetrix® GeneChip® DNA Analysis Software. In two osteosarcoma cases, using unamplified DNA, we identified 793 and 1070 SNP loci with allelic imbalance, respectively. In a parallel experiment with amplified DNA, 78% and 83% of these SNP loci with allelic imbalance was detected. The average false-positive rate is 13.8%. Furthermore, using the Affymetrix® GeneChip® Chromosome Copy Number Tool to analyze the SNP array data, we were able to detect identical chromosomal regions with gain or loss in both amplified and unamplified DNA at cytoband resolution.


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