The Greenwood Genetic Center in South Carolina, USA, provides diagnostic and clinical genetics services to patients with mental retardation and chromosomal abnormalities across South Carolina. OGT’s CytoSure™ arrays are now central to this process, providing excellent resolution and maintaining high throughput screening.

Barbara DuPont is the director of the centre's cytogenetics laboratory, which processes a variety of patient samples for diagnoses, including peripheral blood, bone marrow, tissue culture and amniocenteses for prenatal diagnosis. The cytogenetics laboratory receives about 1,500 peripheral blood samples each year for chromosomal analysis of patients with infertility, children with abnormalities and people with mental retardation or autism of unknown aetiology. These samples largely come from South Carolina, but the Greenwood's DNA and biochemistry diagnostics laboratories also receive samples from across the US and internationally.

“We are using array CGH to look at samples from patients with unknown causes of mental retardation or autism,” Barbara said. “We started using BAC arrays about four years ago and were in the process of moving up from 600 probe arrays to higher resolution BAC arrays when we started having problems with background noise and ozone. In this region, ozone levels become very high during hot weather and this can cause some fluorochromes to quench very quickly, upsetting the fluorescence ratios required for the aCGH and disrupting results. We had o start running controls alongside every sample, and so it was time to switch to a different platform.”

“OGT's software is absolutely fantastic, it is really easy to use,” Barbara commented. “It is ideal for cytogenetics and diagnostics because it gives very clear graphics of the chromosomal changes, and has direct links to the chromosomal variant database, which is very important. For example, if we find a region in a patient's sample with variation, we can click on the region and go directly to the database to see which genes are involved in that variant, and come to a decision straightaway about its significance. We have now re-tested some of the samples we analysed previously using BAC arrays and have picked up a number of abnormalities that were missed before, because of the old arrays' low resolution. The CytoSure arrays are already making a huge difference.”

“I am now so used to looking at the results from 105,000 oligos that when I look back at some of the data from the low resolution BAC arrays I just cringe; we get a lot of extra information with the CytoSure. We can also size chromosomes better, due to the increase in probe concentration. In one instance, we had two patients who appeared to have identical duplication on the old arrays, which did not seem right as the patient phenotypes were not really similar. With the OGT array we were able to establish that they actually had different break points at the 5’ end.”

Barbara continued: “We are now processing between 16 and 24 slides on a weekly basis, but that number keeps going up. In addition we have started using the CytoSure Chromosome X exon specific array, because our research division at the Greenwood does a great deal of investigation into X-linked abnormalities. We see lots of families with unidentified X chromosome-linked genetic problems.”

“OGT is also making us an array for chromosome 22, because we have a special interest in patients and families with chromosome 22q13 deletion (Phelan- McDermid Syndrome), where the bottom part of the chromosome is missing. The Greenwood Genetic Center has been involved with the Chromosome 22q13 amily organisation since it began, and standard chromosomal analysis does not detect this abnormality due to the small size of the region. We have over 100 patient samples from around the world that we will analyse using the 22q13-specific array in order to find out more about the deletion. We are investigating the relationship between the size of the deletion and severity of the patient's mental retardation phenotype, in addition to a possible connection with autism. We are really excited about testing these samples with OGT's oligo array, and are planning to deliver the new data at the Chromosome 22q13 Deletion Foundation's annual meeting. I am confident we can have the samples run by then, as this system gives such clean results.”

“We have had such a wonderful experience working with OGT. Before we started with OGT we had run just about every platform out there. The transition from the BAC platform to this oligo array was so easy, and OGT support staff are wonderful to work with.”