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Project

Identification of susceptibility genes for psychiatric disorders through a functional genomic approach.

Bipolar (BP) disorder and schizophrenia (SZ) are among the most common brain diseases worldwide and result in high social and economical costs in terms of morbidity as well as mortality. Both genetic and environmental factors play an important role in the development of BP disorder and SZ. It is supposed that both disorders result from an interaction of susceptibility genes and/or as a result of complex genetic mechanisms. The aim of this project is to understand the different mechanisms that underlie psychiatric disorders and to determine how important these mechanisms are in the patient populations. These objectives will be realized by examining three hypotheses. These three different ways of thinking all have as primary aim the identification of positional and functional candidate genes for BP disorder and/or SZ.Hypothesis 1: Identification of positional candidate genes on chromosome 6. Our research group found a strong indication for linkage on chromosome 6q23-q24 in nine northern Swedish multigenerational families. Fine-mapping of this region will be done using SNP based genotyping methods. A SNP based association study in large patient/control populations will further reduce the candidate region.Hypothesis 2: Importance of copy number variations on the susceptibility for BP and SZ. The recent literature strongly indicates that copy number variations (CNVs) might be responsible for complex disorders such as BP disorder and SZ. The published potential instable regions will be analysed in our association populations by using an in house developed method (Multiplex Amplicon Quantification MAQ). By doing this we'll gain insight in the significance of genomic instability as the underlying cause of BP disorder and SZ.Hypothesis 3: Post-transcriptional modifications as a cause of BP disorder and SZ. It is assumed that certain mechanisms, like gene regulation, are responsible for complex disorders. A-to-I RNA editing by "Adenosine Deaminases Acting on RNA" (ADAR) is a form of post-transcriptional modification, which is already described for mRNAs coding for the serotonin receptor 5-HTR2C and for the glutamate receptor GRIA2. The different ADAR-genes and target-genes that are possibly related to BP disorder and SZ will be subjected to an association study and/or mutation analysis.
Date:1 Jan 2009 →  31 Dec 2010
Keywords:PSYCHIATRIC DISEASES, FUNCTIONAL GENOMICS, SNP ANALYSIS AND DETECTION, GENETIC ANALYSIS, DNA SEQUENCING
Disciplines:Genetics, Systems biology, Molecular and cell biology, Psychiatry and psychotherapy, Nursing, Other paramedical sciences, Clinical and counselling psychology, Other psychology and cognitive sciences