Genome-wide copy number profiling on high-density bacterial artificial chromosomes, single-nucleotide polymorphisms, and oligonucleotide microarrays: a platform comparison based on statistical power analysis

DNA Res. 2007 Feb 28;14(1):1-11. doi: 10.1093/dnares/dsm002. Epub 2007 Mar 15.

Abstract

Recently, comparative genomic hybridization onto bacterial artificial chromosome (BAC) arrays (array-based comparative genomic hybridization) has proved to be successful for the detection of submicroscopic DNA copy-number variations in health and disease. Technological improvements to achieve a higher resolution have resulted in the generation of additional microarray platforms encompassing larger numbers of shorter DNA targets (oligonucleotides). Here, we present a novel method to estimate the ability of a microarray to detect genomic copy-number variations of different sizes and types (i.e. deletions or duplications). We applied our method, which is based on statistical power analysis, to four widely used high-density genomic microarray platforms. By doing so, we found that the high-density oligonucleotide platforms are superior to the BAC platform for the genome-wide detection of copy-number variations smaller than 1 Mb. The capacity to reliably detect single copy-number variations below 100 kb, however, appeared to be limited for all platforms tested. In addition, our analysis revealed an unexpected platform-dependent difference in sensitivity to detect a single copy-number loss and a single copy-number gain. These analyses provide a first objective insight into the true capacities and limitations of different genomic microarrays to detect and define DNA copy-number variations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Artificial, Bacterial / genetics
  • Gene Dosage*
  • Gene Expression Profiling
  • Genome, Human*
  • Genomics / statistics & numerical data
  • Humans
  • Markov Chains
  • Models, Statistical
  • Oligonucleotide Array Sequence Analysis* / statistics & numerical data
  • Polymorphism, Single Nucleotide