Genetic basis of neurogenetic disorders.

In the past decade considerable progress has been made in unravelling the etiology of important single gene disorders. In the field of neurological and neuropsychiatric diseases only little progress has been made. It is becoming clear that these disorders are complex and may often result from an interplay of genetic and environmental risk factors. Our group is interested to study the genetic basis for a number of “brain” disorders, and the (dys)function of the gene(s) involved.

Goal

The final goal is to identify genes that are involved in common neurogenetic disorders and to study the molecular and biochemical basis of these diseases.

Alzheimer and Parkinson

Still very little is known about genetic factors involved in most cases of dementia.To unravel the genetics of such complex disorders requires a strategy capable of detecting effects of genetic factors, which may depend strongly on the presence of other genetic and/or environmental factors. In collaboration with Van Duijn (Dept of Epidemiology, ErasmusMC) we plan to identify new genes implicated in (late-onset) Alzheimer’s diseases and Parkinson’s disease. The rational of the newly developed method that will be applied is that in a genetic isolated population the number of genes implicated in a heterogeneous disorder is strongly reduced because of genetic drift. Chances that patients have inherited a disease gene from a common ancestor are therefore high and patients from recently isolated populations with a common ancestor likely share considerable parts of DNA around a disease gene. If multiple genes play a role they can be localised simultaneously. This method has been used for the Dj-1 gene which is involved in early onset Parkinson disease. New genes for Alzheimer’s diseases and Parkinson’s disease will be identified and molecular and biochemical role of these disease genes will be studied.