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

Nucleic Acids Res. 2004 May 17;32(9):e69. doi: 10.1093/nar/gnh072.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 6 / genetics
  • False Positive Reactions
  • Genome, Human*
  • Genomics / methods
  • Humans
  • Loss of Heterozygosity / genetics*
  • Microsatellite Repeats / genetics
  • Nucleic Acid Amplification Techniques
  • Oligonucleotide Array Sequence Analysis / methods*
  • Osteosarcoma / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Sensitivity and Specificity