Article

Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH.

Signature Genomic Laboratories, Spokane, WA, USA. .
Molecular Cytogenetics (Impact Factor: 2.66). 01/2010; 3:11. DOI: 10.1186/1755-8166-3-11
Source: PubMed

ABSTRACT Microarray-based comparative genomic hybridization (aCGH) is a powerful diagnostic tool for the detection of DNA copy number gains and losses associated with chromosome abnormalities, many of which are below the resolution of conventional chromosome analysis. It has been presumed that whole-genome oligonucleotide (oligo) arrays identify more clinically significant copy-number abnormalities than whole-genome bacterial artificial chromosome (BAC) arrays, yet this has not been systematically studied in a clinical diagnostic setting.
To determine the difference in detection rate between similarly designed BAC and oligo arrays, we developed whole-genome BAC and oligonucleotide microarrays and validated them in a side-by-side comparison of 466 consecutive clinical specimens submitted to our laboratory for aCGH. Of the 466 cases studied, 67 (14.3%) had a copy-number imbalance of potential clinical significance detectable by the whole-genome BAC array, and 73 (15.6%) had a copy-number imbalance of potential clinical significance detectable by the whole-genome oligo array. However, because both platforms identified copy number variants of unclear clinical significance, we designed a systematic method for the interpretation of copy number alterations and tested an additional 3,443 cases by BAC array and 3,096 cases by oligo array. Of those cases tested on the BAC array, 17.6% were found to have a copy-number abnormality of potential clinical significance, whereas the detection rate increased to 22.5% for the cases tested by oligo array. In addition, we validated the oligo array for detection of mosaicism and found that it could routinely detect mosaicism at levels of 30% and greater.
Although BAC arrays have faster turnaround times, the increased detection rate of oligo arrays makes them attractive for clinical cytogenetic testing.

1 Bookmark
 · 
113 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The clinical utility of microarray technologies when used in the context of prenatal diagnosis lies in the technology's ability to detect sub-microscopic copy number changes that are associated with clinically significant outcomes. We have carried out a systematic review of the literature to calculate the utility of prenatal microarrays in the presence of a normal conventional karyotype. Amongst 12362 cases in studies that recruited cases from all prenatal ascertainment groups, 295/12362 (2.4%) overall were reported to have copy number changes with associated clinical significance (pCNC), 201/3090 (6.5%) when ascertained with an abnormal ultrasound, 50/5108 (1.0%) when ascertained because of increased maternal age and 44/4164 (1.1%) for all other ascertainment groups (e.g. parental anxiety, abnormal serum screening result etc). When additional prenatal microarray studies are included in which ascertainment was restricted to fetuses with abnormal ultrasound scans, 262/3730 (7.0%) were reported to have pCNCs. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 08/2013; · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal of prenatal cytogenetic testing is to provide reassurance to the couple seeking testing for their pregnancy, identify chromosome abnormalities in the fetus, if present, and provide treatments and medical management for affected babies. Cytogenetic analysis of banded chromosomes has been the standard for identifying chromosome abnormalities in the fetus for over 40 years. With chromosome analysis, whole chromosome aneuploidies and large structural rearrangements can be identified. The sequencing of the human genome has provided the resources to develop molecular tools that allow higher resolution observations of human chromosomes. The future holds the promise of sequencing that may identify chromosomal imbalances and deleterious single nucleotide variants. This review will focus on the use of genomic microarrays for the testing and identification of chromosome anomalies in prenatal diagnosis and will discuss the future directions of fetal testing.
    Expert Review of Molecular Diagnostics 07/2013; 13(6):601-11. · 4.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Smith–Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 04/2014; · 2.30 Impact Factor

Full-text (3 Sources)

Download
4 Downloads
Available from
Aug 22, 2014