Schizoid strings attached

January 12, 1996

Schizophrenia may develop earlier and earlier as it passes down the generations.

The discovery is yet another consequence of the discovery several years ago of a significant type of genetic defect - unstable DNA. Since then a cluster of diseases possibly caused by this disruption has been discovered. The discovery also confirms empirical observations on families made long ago but dismissed as artefacts.

Peter McGuffin, of the Institute of Medical Genetics at the University of Wales College of Medicine, and his team have studied the DNA of a group of schizophrenia sufferers and a group of non-sufferers. They presented their work at a recent conference exploring genetic influences on the brain.

DNA is made up of strings of bases, each base represented by scientists with a letter. The scientists were searching for strings of a certain sequence of bases, "CAG". They found longer strings in the sufferers than in the controls.

They believe that they have found another case of "repeat expansion". Every time the DNA copies itself, which happens during reproduction, this little sequence, CAG, repeats itself not once, as it should do, but many times - becoming longer and longer with each successive generation of offspring. The longer the string, the more severe the disease.

In another disease, mytonic dystrophy, sufferers have been found to have at least 50 repeats of a triplet. Those with severe disease can have 1,000.

Professor McGuffin believes that as the string of CAG gets longer the disease may onset earlier. Eventually the string is so long that the disease either becomes so severe that it is fatal - or starts so early that the sufferer's chance of having children is greatly reduced.

Until now the claim that schizophrenia appeared earlier with each generation was dismissed as an artefact that appeared because people watched the children of sufferers more closely for signs of the disease. "It was a bit of a surprise because we have always argued against this observation," said Professor McGuffin.

But schizophrenia is more difficult to unravel than other diseases, such as Huntingdon's Disease and Fragile X syndrome linked with repeat expansion, according to Duncan Shaw, a geneticist at Aberdeen University, who was involved in some of the early discoveries of repeat expansion.

He said that though this prediction is "a pretty good guess" a lot more work needs to be done, for example tying in genetic and environmental causes. "It is quite clear that just having the genes does not always give you the disease."

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