Identification of susceptibility genes for psychiatric disorders through a functional genomics approach.
PhD in Biochemistry & biotechnology
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 complex genetic and environmental factors play an important role in their development.
Our aim is to understand the different mechanisms that underlie these psychiatric disorders. This will be realized by examining three hypotheses, all with the primary aim to identify positional and functional candidate genes for BP disorder and/or SZ.
Identification of positional candidate genes on chromosome 6.
We found a strong indication for linkage on chromosome 6q23-q24 in nine northern Swedish multigenerational families. This region will be fine-mapped by using SNP based genotyping methods, followed by a SNP based association study in large patient/control populations.
Importance of copy number variations (CNVs) on the susceptibility for BP and SZ.
The literature strongly indicates that CNVs might be responsible for complex disorders such as BP disorder and SZ. The 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.
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 several glutamate receptors. The different ADAR- and target-genes that are possibly related to BP disorder and SZ will be subjected to an association study and mutation analysis.
Prof. Dr. Ir. Jurgen Del-Favero
Prof. Rolf Adolfsson, MD