title: 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.
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.
authors.affiliation: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jayne Y
authors.initials: JY
authors.lastname: Hehir-Kwa
authors.forename: Michael
authors.initials: M
authors.lastname: Egmont-Petersen
authors.forename: Irene M
authors.initials: IM
authors.lastname: Janssen
authors.forename: Dominique
authors.initials: D
authors.lastname: Smeets
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
mesh_terms: D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015894:Genome, Human; D023281:Genomics / Q000706:statistics & numerical data; D006801:Humans; D008390:Markov Chains; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide