Genome-wide arrays: Quality criteria and platforms to be used in routine diagnostics

Abstract

Whole-genome analysis using genome-wide arrays, also called "genomic arrays," "microarrays," or "arrays," has become the first-tier diagnostic test for patients with developmental abnormalities and/or intellectual disabilities. In addition to constitutional anomalies, genomic arrays are also used to diagnose acquired disorders. Despite the rapid implementation of these technologies in diagnostic laboratories, external quality control schemes (such as CEQA, EMQN, UK NEQAS, and the USA QA scheme CAP) and interlaboratory comparisons show that there are huge differences in quality, interpretation, and reporting among laboratories. We offer guidance to laboratories to help assure the quality of array experiments and to standardize minimum detection resolution, and we also provide guidelines to standardize interpretation and reporting.

The introduction of arrays in prenatal diagnosis: A special challenge

“…In general, a backbone with a minimal resolution of 200 kb is recommended [Vermeesch et al, 2012]. Many platforms are enriched in gene-dense regions and regions with known microdeletion/microduplication syndromes.…”

“…Experience is best gained by analyzing a sufficient number of patients, thus for most laboratories this means pre-and postnatal samples. The interpretation process is easier if the laboratory has an in-house control dataset, analyzed with the same array platform [Vermeesch et al, 2012].…”

Genome-wide arrays in routine diagnostics of hematological malignancies

“…The arrays contain either nonpolymorphic copy-number probes or polymorphic probes (SNPs), or a combination of both, and each platform has its advantages and limitations, which are discussed below (see also further discussion by Vermeesch et al (2012), this issue).…”

“…Finally, in the diagnostic report, the karyotype is further clarified and relevant genes located in the detected lesions and their clinical relevance (e.g., diagnostic and prognostic impact) should be mentioned with references [see also Vermeesch et al (2012), this issue]. Regarding the reporting of technical information, the guidelines for molecular karyotyping for constitutional genetics diagnosis can be used [Vermeesch et al, 2007[Vermeesch et al, , 2012.…”

“…Microarrays, therefore, allow the identification of very small copy-number aberrations (CNAs) at high accuracy. Although commercially available arrays have been shown to be an indispensable tool for diagnosing patients with intellectual disabilities and/or multiple congenital abnormalities [Vermeesch et al (2012), this issue], it has been more challenging to implement the technology in the diagnostic hematological genetic setting. Nevertheless, array-CGH (aCGH) or SNP arrays have been shown to be a cost-effective alternative to multiple FISH testing to identify genomic imbalances.…”