Definition of a Critical Region on Chromosome 18 for Congenital Aural Atresia by ArrayCGH

Abstract

Deletions of the long arm of chromosome 18 occur in approximately 1 in 10,000 live births. Congenital aural atresia (CAA), or narrow external auditory canals, occurs in approximately 66% of all patients who have a terminal deletion 18q. The present report describes a series of 20 patients with CAA, of whom 18 had microscopically visible 18q deletions. The extent and nature of the chromosome-18 deletions were studied in detail by array-based comparative genomic hybridization (arrayCGH). High-resolution chromosome-18 profiles were obtained for all patients, and a critical region of 5 Mb that was deleted in all patients with CAA could be defined on 18q22.3-18q23. Therefore, this region can be considered as a candidate region for aural atresia. The array-based high-resolution copy-number screening enabled a refined cytogenetic diagnosis in 12 patients. Our approach appeared to be applicable to the detection of genetic mosaicisms and, in particular, to a detailed delineation of ring chromosomes. This study clearly demonstrates the power of the arrayCGH technology in high-resolution molecular karyotyping. Deletion and amplification mapping can now be performed at the submicroscopic level and will allow high-throughput definition of genomic regions harboring disease genes.

Genome-Wide Array-Based Comparative Genomic Hybridization Reveals Multiple Amplification Targets and Novel Homozygous Deletions in Pancreatic Carcinoma Cell Lines

“…Array-based CGH was performed with BAC and cDNA microarrays. 3 The BAC arrays contained a total of 3,565 colonypurified FISH-verified clones, including ϳ3,200 clones selected through an international collaboration to cover the genome with a 1-Mb resolution (20), and clones specifically selected for previous studies (21)(22)(23). Preparation, labeling, hybridization, and scanning procedures for BAC arrays were performed as described in detail by Vissers et al (24).…”

Application of Array-Based Comparative Genomic Hybridization to Clinical Diagnostics

“…19,20 Illustrating the flexibility afforded by this new platform are arrays that have been designed to investigate DNA copy-number changes in individual chromosomes or chromosomal regions, including chromosomes 1, 15, 18, 20, 22, and the X chromosome. 10,[12][13][14]21 In many of these studies, array CGH identified abnormalities that were undetected by either conventional chromosome analysis or FISH.…”

A multiplex PCR predictor for aCGH success of FFPE samples

“…Subsequent development of the technique into array-CGH (also named matrix-CGH) has allowed increased automation, improved reproducibility and precision due to more accurate mapping of aberrations. This technology has been applied successfully to characterise congenital abnormalities at unprecedented precision (Veltman et al, 2002) and to characterise and classify tumours (Wessels et al, 2002;Nessling et al, 2005).In most pathology laboratories, large archives of formalin-fixed, paraffin embedded (FFPE) material are often the only source of material for cancer research. It is our experience (Wessels et al, 2002;Van Beers et al, 2005) that a proportion of archival specimens appears unsuited for aCGH analysis, which is troublesome because array comparative genomic hybridisation (aCGH) experiments are tedious and expensive.…”

“…Subsequent development of the technique into array-CGH (also named matrix-CGH) has allowed increased automation, improved reproducibility and precision due to more accurate mapping of aberrations. This technology has been applied successfully to characterise congenital abnormalities at unprecedented precision (Veltman et al, 2002) and to characterise and classify tumours (Wessels et al, 2002;Nessling et al, 2005).…”