WP08 - DNA bank, SNP-detection and genotyping

The goal of this WP is to prepare and to carry out genotyping of different candidate genes. In our population of 2000 individuals we have 100% power to detect a gene that accounts for 5% of the variance using a p-value of 0.00001. Despite the fact that most neuroimaging studies have demonstrated that genes account for up to 20% of the variance of the phenotypes such studies are relatively few in number. Hence we determined the power of our study to detect genes that only account for 5% of the variance. We also chose a very stringent alpha level of 0.00001, this allows us to correct for 10000 different tests.
Genes will be identified using a whole genome analysis and validated with differentially expressed genes in rat phenotypes selected for extreme response in tasks related to reward, punishment and behavioural control, which have been cross-validated by bioinformatic QTL-analysis of two inbred mouse strains with similar behavioural profiles (see WP1). Based on the gene expression profiling literature and our previous experiences, we expect to identify at least 50 or more genes differentially expressed in the relevant brain regions.

The objectives of WP8 are as follows:

• Ascertainment and storage of blood samples and extraction and quality control of DNA.
• Establishment of immortalized B-lymphoblasts.
• Identification of functional genetic variations in genes associated with human phenotypes.
• Genotyping of haplotype SNPs and functional SNPs in the human sample.  

WP leader is Prof. Dr. Gunter Schumann who holds a Chair in Addiction Biology and is Head of the Section of Addiction Biology at the IoP. He has extensive experience in coordinating multidisciplinary research teams in the context of the German National Genome Research Network and the German Addiction Research Network. He studied medicine at the Universities of Tübingen, Hamburg and Harvard Medical School, where he also worked as a research fellow in the Division of Immunogenetics at the Dana Farber Cancer Research Center. He trained as a psychiatrist at the University of Freiburg and the Central Institute of Mental Health, where he became a consultant in Psychiatry and Head of the Molecular Genetics Laboratory before assuming his present position. His area of expertise covers gene-neuroimaging studies, translational studies and multicentric genetic studies on various drug use-related phenotypes.