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Bonn researchers localise manic depression gene

Press Release No. 01/2002

Yesterday on top of the world, down in the dumps today: manic-depressives suffer from extreme fluctuations of mood. Many such people take their own lives during the phase of depression. An interdisciplinary team headed by the University of Bonn’s Institute of Human Genetics has succeeded in localising a gene which contributes towards the manic depressive disease. The results were recently published in the journal “Human Molecular Genetics”.

Charles Burgess Fry has the reputation of being one of the greatest sportsmen Britain has ever produced. The captain of the England cricket team, who also played football and rugby as well as writing several books about cricket, was an outstanding classical philologist whose hobby was translating English hymns into Greek. The popular partygoer, who was a notorious rake, turned down the Albanian throne in 1919 – allegedly because the position was not salaried. Yet up to his death in 1956 he was prone to phases of unusual hyperactivity alternating with episodes of deep despondency: Fry showed many of the features of manic depression.

About one per cent of all humans suffer, in the course of their lives, from this “bipolar emotional disorder” – and this occurs in all the cultures which have hitherto been investigated. The causes are as yet unknown; therapy is therefore correspondingly difficult. Many of those affected commit suicide during the course of the disease.

What is now known is that genetic factors contribute to the disease. People who display the corresponding genetic features, studies of twins have shown, have a 70% to 80% chance of developing the disease. “We therefore began, twelve years ago, to look for the genes involved,” the Bonn human geneticist Professor Peter Propping explains. Together with researchers from the Psychiatric Clinic, the Biometrics Institute and other psychiatric clinics they have investigated a total of 75 families consisting of 445 persons – 275 of them were manic-depressives. This Herculean task, which was funded by the German Research Association (DFG, Deutsche Forschungsgemeinschaft) could bring its own rewards: “The discovery of the genes involved may lead to the development of new types of therapy,” Prof. Propping adds.

After decoding the human genome the geneticists are now in a situation comparable to that of a linguist who is supposed to translate an extensive text from a completely unknown language into English. They need to find out what the individual words mean in the 23-volume genome dictionary, although they do not even know where a word begins or ends. To make matters more difficult, interspersed between important information, all of a sudden there may be meaningless babble.

When human beings are born, each of them is supplied with two of these “genome dictionaries” – one from their mother, the other from their father –, which they carry around with them in their body cells. Thus the cells contain two items of genetic information for all the hereditary features. When producing egg or sperm cells, the body jettisons the duplicate information and compiles at random a new encyclopedia from the maternal and paternal genome lexicon, in which half the entries are from the father and the other half from the mother. Adjacent entries often come from the same parent – a rule which genome researchers exploit when searching for genes.

If, for example, a child has inherited the gene for blood group A from its father, it is highly probable that the adjacent genes will also be from the father. Similarly, brothers or sisters who both have blood group A therefore often have the same genetic information around the blood group gene. Professor Propping and his team have now investigated siblings suffering from manic depressive disease to discover at which points on their chromosomes the genetic information is markedly similar. To this end they have been scrutinising 400 short genome sections. The result is that some of these sections are especially frequently identical in sick siblings – in their vicinity there may be a gene which contributes to the onset of the disease.

Two sections – one on the long arm of chromosome 8, the second on chromosome 10 – seem to be especially likely candidates. However, both consist of many millions of “letters” and are thus far too big to be sequenced directly and
too large for researchers to be able to compare the sequences of sick and healthy people with one another. “As our next step we are therefore planning to get even closer to the suspect gene by using different methods,” Professor Propping explains, comparing himself to a life form from another planet who is using a telescope to try to find the city of Bonn on Earth. “By now the alien knows that it is somewhere in Germany, but not yet if it’s in the Rhineland or in Swabia.”

Contact: Prof. Peter Propping
Institute of Human Genetics, Universität Bonn
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phone: ++49-228-2872346, fax: ++49-228-2872380