More information - array diagnostics

Array analysis

An array consists of a large collection of small pieces of DNA (probes) attached to a solid surface that can specifically bind to the matching (complementary) counterpart on  a person’s DNA, the human genome. There are so-called Copy Number (CN) probes and SNP (Single Nucleotide Polymorphism) probes. Both can be used to detect genomic imbalances, the CN probes being more robust and more evenly distributed along the genome. The SNP probes are designed to bind only to the complementary piece of DNA if there is an exact match which provides loss of heterozygosity (LOH) data. That enables not only to determine the DNA copy number, copy neutral LOH, but also the genotype (which nucleotide is present at a certain position in the genome) as well. We use the Affymetrix CytoScan HD array platform with a total of nearly 2.7 million copy number markers (1,953,246 CN probes + 743,304 SNP probes) for genome wide SNP array analysis in our diagnostic laboratory.

Identification of germline genomic imbalances

The genotype information from an array experiment can be used for patient-parent trio analysis, to determine the parent of origin of a certain aberration, and to detect uniparental disomy (upd). If parents are (distantly) related, parts of their genome will be the same. This will result in several pieces of identical genomic pieces in their child’s DNA, which is detectable using a SNP array, because the genotypes in these identical pieces will show as AA or BB instead of AB. If one of these identical pieces contains a disease gene with a mutation, the child will be affected. Because we use both the copy number data and the genotype data from our SNP array experiments, we are more likely to find the genetic cause of a patient’s clinical phenotype than laboratories that only look at the copy number data.

Array diagnostics in hematological malignancies

In our diagnostic laboratory we perform genome wide high density array analysis (Affymetrix CytoScan HD) on samples from acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome (MDS) patients. By application of this validated approach we are able to identify specific genomic abnormalities (copy number abnormalities and regions of copy-neutral loss of heterozygosity) which provide important clinical information. Although the conventional techniques such as karyotyping or fluorescence in situ hybridization (FISH) are currently considered as the gold standards to detect such aberrations, these are limited in their resolution and yield. Microarray-based genomic profiling is feasible as an alternative and complementary test. For ALL samples this has resulted in much higher detection rates of genetic abnormalities and the identification of  many small (<5 Mb) genetic lesions, frequently harboring clinically relevant genes such as CDKN2A/B, ETV6, PAX5, and IKZF11,2. In addition, also for MDS and CLL patients, microarray-based genomic profiling identifies genomic abnormalities, which otherwise would remain undetected. 3-6


1) Simons et al., Genes Chrom Cancer 50:969–981, 2011
2) Mullighan et al., N Engl J Med. 360:470-480, 2009
3) Hagenkord et al., JMD 12:184-196, 2010 
4) O’Malley et al., Int Jnl Lab Hem 33: 238-244, 2011 
5) Tiu et al., Blood 117:4552-4560, 2011
6) Starczynowski et al., Blood, 112:3412-3424, 2008