Dimitri Avramopoulos – "Genetics of Schizophrenia: From statistics to biology"
Helyszín: Pszichiátriai és Pszichoterápiás Klinika, Budapest Balassa utca 6.
Helyszín: A klinika tanterme
Over the last decade there has been tremendous progress in identifying genetic loci for schizophrenia. A handful of large copy number variants have been shown to greatly increase the risk. Rare functional variants and de novo mutations have also proven to be important components with presumed strong effects. In addition, over 100 schizophrenia-associated loci have been identified by genome wide association studies (GWAS), each with a small but well proven effect on the risk.
In order to understand the biology linking DNA variation to disease, my laboratory works on approaches to tackle the problems of studying GWAS variants, which are most often not coding, are often in linkage disequilibrium with many others, have uncertain relationships to specific genes and show very small effect sizes. We explore DNA – protein interactions and chromatin conformation to uncover how schizophrenia – associated variation modifies the regulatory landscape. Once we identify functional variants, we employ genome editing to generate cellular models in an isogenic background. The absence of genome-related variance allows us to identify the cellular phenotypes resulting from the introduced schizophrenia risk alleles despite their small effect sizes. I will present examples of such previous work and discuss how they have shaped the current directions of my laboratory.