Head & Contact

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Dr. Lars Bertram
Neuropsychiatric Genetics
Phone:+49 30 8413 1876Fax:+49 30 8413 1139

Neuropsychiatric Genetics

Neuropsychiatric Genetics Group

Scientific overview

The scientific expertise of the Neuropsychiatric Genetics Group lies in the map- ping and characterization of complex disease genes, predominantly in the field of neuropsychiatric diseases. This is achieved by combining genome-wide genotyping and sequencing approaches with bioinformatics and in vitro assays. One of the first papers published since the inception of the Neuropsychiatric Genetics Group was the first ever family-based genome-wide association study (GWAS) in the field of Alzheimer’s disease. This study – which was selected as one of the “Top 10 Medical Breakthroughs in 2008” by Time Magazine – resulted in the identification of CD33 (siglec-3) as a novel genetic risk factor for Alzheimer’s.

This finding was recently replicated by two large international genetic consortia, emphasizing the important role of this gene in Alzheimer’s pathogenesis. In addition to the laboratory work, our group has pioneered the development of bioin- formatic approaches that systematically and quantitatively assesses genetic data for a number of phenotypes including Alzheimer’s disease, Parkinson’s disease, schizophrenia, and multiple sclerosis. More recently, we have initiated several projects that apply “next generation” sequencing to genetically complex diseases. The main project applying these powerful methods searches for novel early-only familial, i.e. disease-causing, Alzheimer’s mutations using exome sequencing. A related and separately funded project utilizes next-generation sequencing for fine-mapping the CD33 locus that our group identified by GWAS in 2008 (see above). The aim of this study is to identify the DNA sequence variant(s) that underlie the GWAS association signal functionally. Another focus of our group lies in the genetic and functional characterization of micro-RNAs in neuropsychiatric diseases. This project, made possible through a Special Research Award of the Hans-and-Ilse-Breuer-Stiftung, uses a combination of systematic in silico and in vitro assessments to predict and experimentally validate the impact of DNA sequence variants on micro-RNA function. In order to increase power and specificity of gene-finding efforts in Alzheimer’s disease, the group has begun to use CSF (cerebrospinal fluid) biomarkers as endophenotypes in genetic association analyses. One successful application of this approach was recently completed in a study where we could show that CSF-Ab levels correlate with polymorphisms at the PICALM locus. Finally, the group has recently received funding to head the genetics core of the “Berlin Aging Study II” (BASE-II), a multicenter study

Locus plot of the ITGA8 region on chromosome 10p13 (15346353-15801533 bp, hg18) recently identified as a novel Parkinson’s disease susceptibility gene by our group (Lill et al. [2012] PLoS Genet). Shown are association results for ~1,400 single nucleotide polymorphisms (SNPs) in the ITGA8 gene region on chromosome 10p13 based on meta-analyses including at least four independent datasets. SNPs are color- coded based on linkage disequilibrium (r2) estimates from the CEU dataset from the 1000 Genomes Projekt (release June 2010).
Locus plot of the ITGA8 region on chromosome 10p13 (15346353-15801533 bp, hg18) recently identified as a novel Parkinson’s disease susceptibility gene by our group (Lill et al. [2012] PLoS Genet). Shown are association results for ~1,400 single nucleotide polymorphisms (SNPs) in the ITGA8 gene region on chromosome 10p13 based on meta-analyses including at least four independent datasets. SNPs are color- coded based on linkage disequilibrium (r2) estimates from the CEU dataset from the 1000 Genomes Projekt (release June 2010). [less]

that aims to identify and characterize factors associated with healthy and unhealthy aging. BASE-II is a collaboration between the MPIMG, MPI for Human Development, Berlin, Charité – Universitätsmedizin Berlin, German Institute for Economic Research, Berlin, and Eberhardt-Karls University, Tübingen.

 
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