Published by De Gruyter

Volume 33 Issue 2

Issue of Medizinische Genetik

Contents
Journal Overview

Publicly Available August 14, 2021

MAIN TOPIC: Mutations in the Non-Coding Genome: From Detection to Clinical Interpretation

Open Access August 14, 2021

Mutation detection in the non-coding genome

Markus Schuelke

Page range: 119-120

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Open Access August 14, 2021

What can go wrong in the non-coding genome and how to interpret whole genome sequencing data

Heiko Krude, Stefan Mundlos, Nancy Christine Øien, Robert Opitz, Markus Schuelke

Page range: 121-131

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Abstract

Whole exome sequencing discovers causative mutations in less than 50 % of rare disease patients, suggesting the presence of additional mutations in the non-coding genome. So far, non-coding mutations have been identified in less than 0.2 % of individuals with genetic diseases listed in the ClinVar database and exhibit highly diverse molecular mechanisms. In contrast to our capability to sequence the whole genome, our ability to discover and functionally confirm such non-coding mutations is lagging behind severely. We discuss the problems and present examples of confirmed mutations in deep intronic sequences, non-coding triplet repeats, enhancers, and larger structural variants and highlight their proposed disease mechanisms. Finally, we discuss the type of data that would be required to establish non-coding mutation detection in routine diagnostics.

Open Access August 14, 2021

Novel sequencing technologies and bioinformatic tools for deciphering the non-coding genome

Jana Marie Schwarz, Richard Lüpken, Dominik Seelow, Birte Kehr

Page range: 133-145

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Abstract

High-throughput sequencing techniques have significantly increased the molecular diagnosis rate for patients with monogenic disorders. This is primarily due to a substantially increased identification rate of disease mutations in the coding sequence, primarily SNVs and indels. Further progress is hampered by difficulties in the detection of structural variants and the interpretation of variants outside the coding sequence. In this review, we provide an overview about how novel sequencing techniques and state-of-the-art algorithms can be used to discover small and structural variants across the whole genome and introduce bioinformatic tools for the prediction of effects variants may have in the non-coding part of the genome.

Open Access August 14, 2021

Technologies for profiling the impact of genomic variants on transcription factor binding

Janna Leiz, Maria Rutkiewicz, Carmen Birchmeier, Udo Heinemann, Kai M. Schmidt-Ott

Page range: 147-155

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Abstract

Transcription factors (TFs) bind DNA in a sequence-specific manner and thereby regulate target gene expression. TF binding and its regulatory activity is highly context dependent, and is not only determined by specific cell types or differentiation stages but also relies on other regulatory mechanisms, such as DNA and chromatin modifications. Interactions between TFs and their DNA binding sites are critical mediators of phenotypic variation and play important roles in the onset of disease. A continuously growing number of studies therefore attempts to elucidate TF:DNA interactions to gain knowledge about regulatory mechanisms and disease-causing variants. Here we summarize how TF-binding characteristics and the impact of variants can be investigated, how bioinformatic tools can be used to analyze and predict TF:DNA binding, and what additional information can be obtained from the TF protein structure.

Open Access August 14, 2021

How to find genomic regions relevant for gene regulation

Xuanzong Guo, Uwe Ohler, Ferah Yildirim

Page range: 157-165

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Abstract

Genetic variants associated with human diseases are often located outside the protein coding regions of the genome. Identification and functional characterization of the regulatory elements in the non-coding genome is therefore of crucial importance for understanding the consequences of genetic variation and the mechanisms of disease. The past decade has seen rapid progress in high-throughput analysis and mapping of chromatin accessibility, looping, structure, and occupancy by transcription factors, as well as epigenetic modifications, all of which contribute to the proper execution of regulatory functions in the non-coding genome. Here, we review the current technologies for the definition and functional validation of non-coding regulatory regions in the genome.

Open Access August 14, 2021

Public data sources for regulatory genomic features

Samuele Garda, Jana Marie Schwarz, Markus Schuelke, Ulf Leser, Dominik Seelow

Page range: 167-177

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Abstract

High-throughput technologies have led to a continuously growing amount of information about regulatory features in the genome. A wealth of data generated by large international research consortia is available from online databases. Disease-driven studies provide details on specific DNA elements or epigenetic modifications regulating gene expression in specific cellular and developmental contexts, but these results are usually only published in scientific articles. All this information can be helpful in interpreting variants in the regulatory genome. This review describes a selection of high-profile data sources providing information on the non-coding genome, as well as pitfalls and techniques to search and capture information from the literature.

BERICHTE AUS DER HUMANGENETIK

Oral-History-Projekt der GfH

August 14, 2021

Das Oral-History-Projekt – Lehren aus der Geschichte unseres Faches

Klaus Zerres

Page range: 179-179

Open Access August 14, 2021

Oral-History-Projekt Humangenetik: Historische Forschungsmethode zur Erhebung und Weiterverarbeitung narrativer Interviews

F. Söhner, H. Fangerau, M. Krischel

Page range: 181-187

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Abstract

Zusammenfassung Zwischen 2016 und 2018 wurden mit 33 Personen Interviews zur Geschichte der Humangenetik in Deutschland zwischen 1970 und den 2000er Jahren geführt. 29 Interviewte stimmten einer wissenschaftlichen Analyse zu. Diese Interviews wurden mit den Methoden der qualitativen Inhaltsanalyse und der Grounded Theory ausgewertet. Im Zentrum dieses Beitrags steht die kritische Auseinandersetzung mit der Methode der Oral History und ihrer Anwendung auf die Humangenetik. Das Oral-History-Projekt konzentriert sich auf Fragen zu (1) biographischen Daten und Werdegang der Gesprächspartner*innen, (2) Entwicklung und Anwendung von diagnostischen und therapeutischen Techniken, (3) Etablierung und Ausbau der Institutionen der Humangenetik und (4) der Wahrnehmung der das Fach betreffenden gesellschaftlichen Debatten.

Open Access August 14, 2021

Geschichtsbewusstsein und historische Verantwortung in der deutschen Humangenetik

M. Krischel, H. Fangerau, F. Söhner

Page range: 189-195

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Abstract

Zusammenfassung Historiker*innen haben immer wieder auf personelle und institutionelle Kontinuitäten zwischen der Eugenik in Deutschland vor 1945 und der sich entwickelnden Humangenetik im Nachkriegsdeutschland hingewiesen. Wie aber wurde diese äußere Wahrnehmung unter deutschen Humangenetiker*innen diskutiert und spielte sie für das Selbstbild der Disziplin eine Rolle? Auf der Basis von gedruckten Quellen und biographischen Interviews wurden das Geschichtsbewusstsein und die Übernahme historischer Verantwortung unter deutschen Humangenetiker*innen untersucht, die in der Zeit zwischen den 1970er und den 2010er Jahren im Feld tätig waren. Ein historisches Bewusstsein spielte in der Erinnerung der Zeitzeug*innen schon vor den 1980er Jahren eine Rolle für ihr Fach und seit der Gründung der Deutschen Gesellschaft für Humangenetik im Jahr 1987 wird in der Gesellschaft die Frage der Form einer historischen Verantwortungsübernahme immer wieder diskutiert. Sie findet ihren praktischen Ausdruck z. B. in Diskussionen mit der Öffentlichkeit und in der Umbenennung von Preisen.

GfH-Verbandsmitteilungen

August 14, 2021

Protokoll der Informationsveranstaltung zur 33. Ordentlichen Mitgliederversammlung der Deutschen Gesellschaft für Humangenetik (GfH)

Page range: 197-202

BVDH-Verbandsmitteilungen

August 14, 2021

Kontinuität und Wandel – Vorstandswahl 2021: Generation X statt Generation Golf

Page range: 203-204

August 14, 2021

Position für einen neuen Vorstand des BVDH

Page range: 205-206

August 14, 2021

Einladung zur 25. Mitgliederversammlung des Berufsverbandes Deutscher Humangenetiker am 27. November 2021 in Köln

Page range: 207-208

Aktuelle Nachrichten

August 14, 2021

Aktuelle Nachrichten

Page range: 209-218

About this journal

Objectives

medizinischegenetik serves education and training among colleagues, the interdisciplinary exchange of knowledge in all areas of human genetics in clinics, practice, research and teaching. Each issue of the quarterly journal deals with a focus that provides a comprehensive overview of current developments in specific clinical pictures, technical developments and therapeutic approaches. All reviews are written in English language. The journal thus creates a platform for the international exchange of knowledge and increased awareness of German research activities in the scientific community.

In addition, medizinischegenetik contains information on activities in its own subject in the German-language section. This includes conference reports, association announcements, personnel matters, statements and guidelines. With health policy questions, historical retrospectives and comments on current developments, the profession takes a stand on human genetic issues in Germany, Austria and Switzerland.

Main Topics for the coming issues are:

Genomics and Epigenomics of Psychiatric Disorders

Hereditary Hearing Loss and Deafness Overview

Periphere Neurogenetic Disorders

Genomic Imprinting

Volume 33 Issue 2

Issue of Medizinische Genetik

Frontmatter

Mutation detection in the non-coding genome

What can go wrong in the non-coding genome and how to interpret whole genome sequencing data

Abstract

Novel sequencing technologies and bioinformatic tools for deciphering the non-coding genome

Abstract

Technologies for profiling the impact of genomic variants on transcription factor binding

Abstract

How to find genomic regions relevant for gene regulation

Abstract

Public data sources for regulatory genomic features

Abstract

Das Oral-History-Projekt – Lehren aus der Geschichte unseres Faches

Oral-History-Projekt Humangenetik: Historische Forschungsmethode zur Erhebung und Weiterverarbeitung narrativer Interviews

Abstract

Geschichtsbewusstsein und historische Verantwortung in der deutschen Humangenetik

Abstract

Protokoll der Informationsveranstaltung zur 33. Ordentlichen Mitgliederversammlung der Deutschen Gesellschaft für Humangenetik (GfH)

Kontinuität und Wandel – Vorstandswahl 2021: Generation X statt Generation Golf

Position für einen neuen Vorstand des BVDH

Einladung zur 25. Mitgliederversammlung des Berufsverbandes Deutscher Humangenetiker am 27. November 2021 in Köln

Aktuelle Nachrichten