Allele-specific expression

Coordinator:		PD Dr. rer. nat. Sven Cichon
Institution:		Department of Genomics, Life & Brain Center, University of Bonn
Homepage:		www.lifeandbrain.com/mid102_Genomics.html

Much of the genetic component of human phenotypic diversity has been proposed to be the result of a genetically determined variability in gene expression. Several recent studies have stressed the extent to which gene expression varies within and between populations, and have shown that allele-specific expression is relatively common among autosomal genes. Further, there is evidence that a portion of the inherited variation in gene expression may play an important role in susceptibility to complex diseases. While genetic factors have been identified that influence gene expression in peripheral tissues (blood cells), such data is not yet available on human fresh brain tissue. This information would be highly desirable for the quest for genetic factors contributing to the development of complex neuropsychiatric diseases. In the present study, we aim at mapping genetic determinants of gene expression in human hippocampal segments derived from epilepsy-surgery. The University of Bonn harbours a major center for neurosurgery and one of the largest hippocampal fresh frozen tissue banks world-wide.
For systematic mapping of determinants for hippocampal gene expression, we are currently isolating DNA and RNA of 150 hippocampus samples taken from the Bonn tissue bank which then undergo a genome-wide association study (GWAS) and gene expression (GEX) analysis. Each individual DNA sample is genotyped for 660,000 single nucleotide polymorphisms (SNPs). Individual gene expression levels for more than 99,9% of all known human genes are interrogated with microarrays containing more than 48,000 probes. Gene expression levels are then systematically correlated with individual genotype information. An important application of our findings will be the interpretation of GWAS results for neuropsychiatric disorders (schizophrenia, bipolar disorder, unipolar depression) that are currently generated in the course of the NGFNplus-integrated genome research network “MooDS”.