| OGT’s CytoSure™ arrays are helping clinical geneticists in Denmark to investigate chromosomal changes in patients with a variety of disorders. All routine clinical screening was previously carried out on BAC arrays, however recent testing has highlighted the advantages of OGT’s oligo arrays. This technology offers clinical geneticists a powerful new tool for genome wide screening, with detection of many previously unidentified chromosomal changes now possible.
As an initial trial, several patient samples of particular interest were taken from Denmark to OGT's laboratories in Oxford, where they were analysed using the CytoSure Syndrome Plus v2 arrays, and the data obtained was compared with the clinical laboratory’s previous findings from the low probe density BAC arrays. The high resolution of OGT's 105,000-probe arrays provided far greater detail and accuracy in describing the patients' chromosomal abnormalities, demonstrating the clinical potential of this powerful technology. |
The advantages of the Syndrome Plus arrays’ high resolution are most clearly demonstrated by small chromosomal deletions, such as the small terminal deletions common in ring chromosome formation. These are often phenotypically
significant, and the 175-fold greater probe density of the OGT array is able to detect many aberrations that are not apparent using BAC arrays. For example, one of the samples tested by the Danish team was from a patient suffering an extremely rare ring chromosome 9 disorder. Originally diagnosed using fluorescent in situ hybridisation (FISH) analysis, a deletion in the q-arm of the ring chromosome was undetectable on low resolution BAC arrays due to its small size of approximately 0.4 Mb. By comparison, this deletion was detected by 76 probes on the Syndrome Plus array. Another deletion, in the p-arm, was only detected by a single probe on the BAC, compared with 294 probes on the oligo array. These examples demonstrate how high resolution provides clinical geneticists with much greater confidence in determining if an aberration is simply an artefact or a genuine chromosomal change. While an apparent abnormality detected by just one or two probes on a low resolution
array could be an artefact, the overlapping oligo probes virtually eliminate this possibility.
The high resolution is also advantageous in determining the likely impact of a genetic variation. An aberration detected by a single probe on a BAC array could potentially be linked to several adjacent genes covered by the probe. By comparison, an aberration detected by just a few oligo probes relates to only a very small region of the chromosome, offering the investigator far greater insight into the likelihood of that abnormality being responsible for an observed phenotype. Equally important, particularly in the study of idiopathic conditions, is the capacity of the CytoSure arrays to rule out chromosomal disorders. With high resolution data it becomes possible to almost entirely eliminate a genetic cause of a given condition, whereas confidence in low resolution analysis is rarely good enough to allow this. Critics of high resolution aCGH technology cite complex data handling and interpretation as the drawbacks of such technologies, however the Danish investigators found OGT’s purpose-built software easy to understand and quick to use: “The advantage of having a software solution specifically focused for clinical genetics use is that a lot of additional, useful information and links to various relevant databases have been incorporated into the package. This makes it a powerful tool, giving clear and detailed results without background interference.” The aCGH screening project in Denmark has now completed validation of the oligo arrays for clinical use, and has transferred all screening to OGT’s arrays, improving diagnosis and offering patients better care. |
