As science delves deeper into DNA, even well-funded, imaginative researchers can find themselves limited by technology.

Trying to relate specific genes to specific medical disorders is like looking for needles in a huge haystack, but now the University of Otago has state-of-the-art tools to help the search.

Comparative genomic hybridisation (CGH) is proving a boon for clinical geneticist Professor Stephen Robertson, from the Dunedin School of Medicine.

"The latest CGH technology allows us to at least search the haystack systematically," says Robertson, who holds the Cure Kids Chair in Child Health Research.

Robertson is trying to identify genes implicated in a variety of diseases that strike families and affect the development of the skeleton and brain.

"Many disorders that affect the development of these structures and are evident at birth will have a genetic cause," says Robertson. "If we can discover more about them, we may be able to offer the parents of a child with a problem a more accurate prognosis, or assign a more accurate estimation of the risk that the problem may recur in a subsequent child."

Robertson and PhD student Margriet van Kogelenberg are particularly interested in problems characterised by faulty wiring within the brain - socalled neuronal migration disorders.

Nerve cells are born in the middle of an embryo's brain. They then typically migrate to their ultimate location - the cerebral cortex - where they make electrical connections with their neighbours to build a normally-wired brain.

"With this high resolution we can see if elements of any person's genetic constitution have been deleted, rearranged or doubled up."

Sometimes the fine-tuning goes wrong. Neurons make wrong connections or don't connect at all, resulting in abnormal brain function. This can result in a number of problems, ranging from learning difficulties through to having seizures.

MRI scans can show that patients may have nodules of neurons that never left their birthplace, but it's hard to pin down why this happens.

"We're using CGH to explore the possibility that certain genetic defects may lead to this situation occurring. If we can identity these critical genes, we may be able to help families who have individuals with neuronal migration problems," says Robertson.

Until recently, standard chromosome tests taken from patients' blood samples were studied through a microscope to see if there were abnormalities. But, at best, this optical testing allowed only about 1,000 data points to be checked to see if they were in the right order, location and number.

Now new CGH technology allows researchers to spread patients' DNA prepared from their chromosomes onto a microscope slide, where two million data points can be individually examined for discrepancies.

"With this high resolution we can see if elements of any person's genetic constitution have been deleted, rearranged or doubled up. We can then take these genetic signals as possible indicators of where critical genes for neuronal migration may lie in the human genome," says Robertson.

"Not every patient with a neuronal migration disorder is going to have one of those abnormalities, but the rare one that does might be our own Rosetta Stone, leading us to a particular part of a particular chromosome that could hold an answer to a critical gene, or genes, that direct neuronal migration."

Funding from Cure Kids helps meet the high costs involved in investigating each patient. Robertson believes the potential gain will be worth it.

"Medicine always aims to add precision to diagnosis, and we hope this work will help us understand more about these diseases and their ultimate cause."

Funding