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Estonian-Cypriot Researchers Say Array MAPH May Complement Cytogenetics Labs

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Researchers from Estonia and Cyprus have optimized an array-based methodology they believe will give cytogeneticists an extra tool in their laboratories, according to team members.

Ants Kurg, an investigator at the Institute of Molecular and Cell Biology at Tartu University in Estonia and Philippos Patsalis, head of Cytogenetics Department of the Cyprus Institute of Neurology and Genetics, told BioArray News this week that multiplex amplifiable probe hybridization methodology, or array MAPH, could be used in cytogenetics labs as a way to confirm results obtained from array comparative genomic hybridization.

Specifically, MAPH takes advantage of multiplex step- and probe-design capabilities that give it a stronger way of looking at the human genome, Kurg and Patsalis said.

"With array CGH you label the total genomic DNA. In the case of MAPH, the probes have been directly targeted to certain loci in the genome," Kurg said. Because of the amplification step and probe design, he said the user "can take MAPH and go deeper" looking into specific telomeric or chromosomal regions for deletions.

Working together, the Nicosia-based CING and the IMCB co-authored a paper in the July-September edition of the European Journal of Medical Genetics, and said that the method could be used in a variety of ways, specifically in detecting deletions in patients suffering from mental retardation, as well as for arrayCGH validation.

"In the case of mental retardation we are dealing with a +1/-1 copy number change, so it is not so easy to see that using arrayCGH," Kurg said. He added that "there are a lot of different aCGH methods out there and all of them need some way to confirm" results. "One way is array MAPH."

Patsalis told BioArray News in an e-mail that the team cannot "say that array-MAPH can be a replacement for array-CGH. It is more like an alternative or complementary methodology," he said.

According to Patsalis, his research group helped initiate the work on MAPH in 2001 as an attempt to move the methodology from slab-gel-based electrophoresis onto arrays. His team was also responsible for "creating the first few steps of the team's methodology, while the Tartu group offered its experience in hybridization onto arrays and analysis software, which was developed by [IMCB's bioinformatics]."

To test the methodology, the teams have used MAPH in a dozen or so cases successfully, and they said that they are preparing to publish another paper highlighting their results.

"Our next step is to further validate and improve the method by screening a number of patients with unexplained mental retardation and proceed with the respective publications," Patsalis said this week.

The Cyprus team said that if the methodology proves reliable they will begin offering through their clinic it as a service to sufferers of mental retardation.

"After we have proved [the] cost-effectiveness, high sensitivity, and resolution of our approach, we can think of offering it as a service to a group of patients in Cyprus, as we are a diagnostic center as well," Patsalis said.

In addition, the team will continue to tout its method via publication, and occasionally, in person — Kurg spoke about the method at the American Society of Human Genetics meeting in Salt Lake City two weeks ago, and Ludmila Kousoulidou, a post-doctoral scientist in Patsalis' team, presented the technology at an ArrayCGH meeting in Bari, Italy, in mid-October.

Patsalis also said that he is eyeing new avenues for the method. Because of flexibility with regards to probe design, the team is now in a place where it can "consider other applications of array-MAPH and to establish new collaborations."

— Justin Petrone ([email protected])

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