27/11/2017 – Researchers from the Universities of Basel, Bonn and Cologne create a systematic catalog in front of variable sites in the genome that influence gene activity in the human hippocampus.
New findings help in Identifzierung genetic causes of brain diseases: researchers from the Universities of Basel, Bonn and Cologne create a systematic catalog in front of certain variable sites in the genome that influence gene activity in the human hippocampus, as they report in the journal “Nature Communications”.
The emergence of many multifactorial diseases individual differences in gene regulation contribute. It is therefore attempted to elucidate the effect of genetic variants (single nucleotide polymorphisms, SNPs) on gene expression and epigenetic modification of regulatory regions of the genome (DNA methylation). The German-Swiss team has now investigated the genetic determinants of gene expression and DNA methylation in the hippocampus of man.
3 million gene Tellen investigated
The researchers place an extensive catalog of variable sites in the genome – the SNPs – before acting in the human hippocampus on the activity of genes. Specifically, it analyzed the influence of more than 3 million over the whole genome SNPs distributed on the activity of nearby genes and lying on the methylation of adjacent DNA regions.
The special feature is that the researchers used fresh frozen hippocampal tissue derived from the surgical treatment of 110 drug-resistant epilepsy patients. They extracted the DNA and RNA from hippocampus tissue and determined in all samples using a plurality of microchips 100,000 SNPs, and the degree of methylation at multiple locations 100,000 (so-called CpG dinucleotides) in the genome. Among others, the gene expression was measured from over 15,000 genes by RNA microchips.
Development of schizophrenia
Next, the researchers demonstrated, in which areas of the genome variably methylated CpG dinucleotides are preferred, and could assign them specific regulatory elements. Here, a reference to diseases of the brain showed: A significant proportion of SNPs found individually affect the hippocampus DNA methylation and gene expression, also contributes to the development of schizophrenia. This highlights the potential importance of effective regulatory SNPs for the emergence of diseases of the brain.
The study results will aid in the interpretation of genetic association findings for brain diseases in the future significantly. Many of the identified SNPs in recent years, which are involved in the development of diseases of the brain that are in the non-coding part of the genome, which is why their functional effect in the cells is mostly unclear.
An important role in the success of the project played the close cooperation between the Universities of Bonn, Cologne and Basel, the promoted German Federal Ministry of Education and Research through the joint project “Integra Movement”; Coordinator is Prof. Dr. Markus Nöthen of the University of Bonn.