title: High-throughput analysis of subtelomeric chromosome rearrangements by use of array-based comparative genomic hybridization.
abstract: Telomeric chromosome rearrangements may cause mental retardation, congenital anomalies, and miscarriages. Automated detection of subtle deletions or duplications involving telomeres is essential for high-throughput diagnosis, but impossible when conventional cytogenetic methods are used. Array-based comparative genomic hybridization (CGH) allows high-resolution screening of copy number abnormalities by hybridizing differentially labeled test and reference genomes to arrays of robotically spotted clones. To assess the applicability of this technique in the diagnosis of (sub)telomeric imbalances, we here describe a blinded study, in which DNA from 20 patients with known cytogenetic abnormalities involving one or more telomeres was hybridized to an array containing a validated set of human-chromosome-specific (sub)telomere probes. Single-copy-number gains and losses were accurately detected on these arrays, and an excellent concordance between the original cytogenetic diagnosis and the array-based CGH diagnosis was obtained by use of a single hybridization. In addition to the previously identified cytogenetic changes, array-based CGH revealed additional telomere rearrangements in 3 of the 20 patients studied. The robustness and simplicity of this array-based telomere copy-number screening make it highly suited for introduction into the clinic as a rapid and sensitive automated diagnostic procedure.
authors.affiliation: Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands. j.veltman@antrg.azn.nl
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
authors.forename: Eric F P M
authors.initials: EF
authors.lastname: Schoenmakers
authors.forename: Bert H
authors.initials: BH
authors.lastname: Eussen
authors.forename: Irene
authors.initials: I
authors.lastname: Janssen
authors.forename: Gerard
authors.initials: G
authors.lastname: Merkx
authors.forename: Brigitte
authors.initials: B
authors.lastname: van Cleef
authors.forename: Conny M
authors.initials: CM
authors.lastname: van Ravenswaaij
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Dominique
authors.initials: D
authors.lastname: Smeets
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016615:Telomere / Q000235:genetics*; D013997:Time Factors