Which is the largest RNA
How cells work: genetic program decoded
Dr. Boris Pavlovsky Press, communication and marketing
Christian Albrechts University in Kiel
World's largest study with RNA sequencing with German participation
Scientists from all over Europe, including research groups from Kiel and Berlin, have deciphered the genetic program according to which cells function in a comprehensive study. In the world's largest RNA sequencing analysis to date, they bring more than 450 entire genome sequences into connection with their translation into RNA, the gene activity. The results of the study were published today, September 15, in two publications in the journals Nature and Nature Biotechnology.
In recent years, new methods have enabled rapid advances in human genome analysis. Scientists can read out a complete human genome, i.e. the sequence of letters in DNA, within a few days. In recent years, through numerous large-scale projects, such as the “1000 Genome Project”, they have created numerous maps of the DNA variants, changes in individual building blocks in different human populations. This knowledge is necessary to describe genetic changes that increase the risk of disease. However, it is largely not understood how this genetic variation is translated into different functions in cells. Many of the disease variants are located in regions that do not have a direct influence on the gene products. But they are in regulatory areas that determine which genes are active or inactive and when. In this study, this relationship was examined extensively for the first time in a large number of individuals.
For the study, published in the journal Nature, around 50 scientists from eight European institutions, including the Christian-Albrechts-Universität zu Kiel (CAU) in Germany, the University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, the Max-Planck- Institute for Molecular Genetics (MPIMG), Berlin, as well as the Helmholtz Center Munich, the gene activity (RNA) measured in cells. Led by Professor Emmanouil Dermitzakis from Geneva University, the team sequenced the RNA, a copy of the genetic information that is responsible for the function of the genes in the cell, from 462 individuals. The accompanying publication in Nature Biotechnology describes new standards for the production of large data sets from RNA sequencing.
The variety of genetic variations that influence the regulation of most of our genes surprised the scientists, said Dr. Tuuli Lappalainen, formerly Geneva, now Stanford University, lead author of the study. In the evaluation, the scientists compared the data from the RNA sequencing with the genome sequences of the same people who were already analyzed as part of the 1000 Genome Project.
"We now not only know how different the book of genes can look, but also how it is read," says Professor Philip Rosenstiel, Director at the Institute for Clinical Molecular Biology (IKMB) at the CAU and UKSH. Parts of the sequencing and data analysis were carried out in his working group at the IKMB. Having helped shape these results is a real success, said Rosenstiel. However, it also shows that such large studies can only come about through the collaboration of many international scientists.
“Understanding the genetic variants that cause the different activity of genes in different people can give us clues as to why drugs work in some patients, but no positive improvements can be seen in others. This can give us indications for the development of an improved therapy tailored to the individual patient, ”explains Prof. Hans Lehrach, Director at the Max Planck Institute for Molecular Genetics in Berlin. And Ralf Sudbrak, a former employee of the MPIMG, who is now employed by the company Alacris Theranostics GmbH, adds: “The participation in the decoding of the functional genetic differences in different human populations was a logical continuation of the 1000 Genome Project, in which the MPIMG is also involved. The datasets of this study together with the data from the 1000 Genome Project form a common reference of the variation and function of the human genome. "
Understanding the range of genetic variants that individually influence cellular programs not only provides information for basic science, but also for possible biomarkers and therapeutic goals for a whole range of diseases. “It is precisely this insight into the cellular programs that gives the clinician an explanation of how environmental influences and lifestyle can lead to chronic diseases,” says Stefan Schreiber, professor at the Medical Faculty of the CAU, director of the Clinic for Internal Medicine I and also author of the study . "We expect that this will result in very specific starting points for personalized therapies and, above all, health-preserving preventive procedures."
"Transcriptome and genome sequencing uncovers functional variation in humans"
Nature: http://dx.doi.org/, DOI: 10.1038 / nature12531
The study is a project of the Genetic European Variation in Disease (GEUVADIS) consortium. GEUVADIS brings together 17 institutions from seven different countries. Its aim is to gain new knowledge about the human genome and its role in diseases through sequencing and the exchange of data.
The Institute for Clinical Molecular Biology (IKMB) of the CAU and the UKSH in Kiel focuses on translational research and clinical implementation of molecular biological research approaches in the field of diseases of the barrier organs such as the lungs and intestines. Internationally visible contributions have been made in recent years in the description of the genetic and functional risk maps as well as the uncovering of a disturbed balance between the human immune system and the intestinal microflora as the cause of these diseases.
The Max Planck Institute for Molecular Genetics (MPIMG) in Berlin is one of the leading genome research institutions in Europe. It comprises four departments, an independent research group and a number of also independent junior research groups ("Otto-Warburg" Laboratorium "). Research at the MPIMG focuses on the analysis of the genome of humans and other organisms. It thus contributes to a comprehensive understanding of biological processes in the organism and to the elucidation of the molecular causes of many human diseases. The aim of the joint efforts of all groups of the MPIMG is to gain new insights into the development of diseases at the molecular level in order to contribute to the development of treatment methods that are appropriate to the cause.
Prof. Philip Rosenstiel
Institute for Clinical Molecular Biology
Tel .: 0431 597-5101
Email: [email protected]
In Berlin: Dr. Patricia Marquardt, Press and Public Relations
Max Planck Institute for Molecular Genetics
Tel .: 030 8413-1716
Email: [email protected]
Christian Albrechts University in Kiel
Press, communication and marketing, Dr. Boris Pavlovsky
Postal address: D-24098 Kiel, phone: (0431) 880-2104, fax: (0431) 880-1355
e-mail: [email protected]
Text / editing: ► Dr. Ann-Kathrin Wenke
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