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How can we improve the identification and prompt diagnosis of genetic diseases? A new Research Unit at Charité – Universitätsmedizin Berlin will set out to identify and reliably interpret important non-coding sections of our genomes in the hope of finding the diagnosis for unsolved diseases. The researchers’ objective is to develop software capable of analyzing whole-genome data in the clinical setting. The Research Unit, which is being funded by the German Research Foundation (DFG) will receive approximately €3.5 million over a period of three years.

Only about three percent of our DNA encodes the genetic blueprints needed for protein synthesis. These protein-coding sections of DNA are referred to as ‘genes’. The remaining 97 percent of our genetic information consists of non-protein-coding DNA sequences, the precise function of which is not yet fully understood. While some of these sections are known to regulate the activity of protein-coding genes, the precise gene sequences and processes involved remain largely unknown. It is precisely this gap in our knowledge which the new Research Unit hopes to address. Led by Prof. Dr. Markus Schülke of Charité’s Department of Pediatrics, Division of Neurology, the researchers hope to improve our understanding of non-coding DNA sequences with a view to speeding up the diagnosis of patients with unexplained rare genetic diseases. Efforts to date have focused solely on protein-coding sections of the DNA. As a result, current gene sequencing techniques are only capable of identifying approximately 50 percent of disease-causing genetic changes. Mutations in non-coding or regulatory DNA sequences are overlooked.

The interdisciplinary Research Unit will see medical specialists work alongside experts from the fields of genetics, molecular biology, cell biology, structural biology and bioinformatics. Their goal is to take the next step towards practicable solutions for the diagnosis of rare genetic diseases – the reliable interpretation of results obtained via whole-genome sequencing. However, while this technology is capable of determining the three billion base pairs that make up our genome, it is not yet suitable for use in clinical practice. This is partly due to the enormous amount of non-coding DNA, as well as our relative dearth of knowledge about them, which makes it difficult for us to interpret genetic changes in the largest part of the human genome.

“The aim of our new research collaboration is to enhance our understanding of gene regulation and gene transcription, in addition to developing a freely accessible, user-friendly software for whole-genome sequencing data analysis. Use of this software should be possible even in the absence of any specific prior knowledge in bioinformatics. We hope our research will help move whole-genome analysis closer to the patient’s bedside and, as a result, deliver a diagnosis to our patients,” explains Prof. Schülke, who is also a Research Group leader at the NeuroCure Custer of Excellence and a Member of ECN.

The new Unit will study genome data collected from groups of patients with congenital disorders affecting thyroid and musculoskeletal development. Based on these data, the researchers will develop algorithms and general rules for the interpretation of non-coding gene sequences which will also be suitable for use with other disorders.

Contact: Prof. Dr. Markus Schülke
Department of Pediatrics, Division of Neurology
NeuroCure Cluster of Excellence
Charité – Universitätsmedizin Berlin

Email: markus.schuelke(at)charite.de

Source: Press Release Charité-Universitätsmedizin

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