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Genetische Untersuchungen an Kindern mit schweren bakteriellen Infektionserkrankungen

Genetic investigations in children with severe bacterial infectious diseases

  • Leitthema
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Zusammenfassung

Durch die rasanten Fortschritte der Molekulargenetik ist es möglich, das gesamte Genom des Menschen systematisch zu untersuchen und die Gene zu identifizieren, die für das Auftreten und die verschiedenen Verläufe von Infektionserkrankungen verantwortlich sind. Frühere genetische Analysen umfassten Zwillingsstudien sowie Studien an Adoptivkindern, „Linkage“-Analysen und Assoziationsstudien mit Kandidatengenen. Neuere Methoden untersuchen das gesamte Genom (GWAS) oder Exom („exome sequencing“) gleichzeitig auf mögliche Assoziationen zu bestimmten Krankheiten und Krankheitsverläufen. Genexpressionsanalysen befassen sich mit der spezifischen Reaktion des Erkrankten und versprechen damit, zukünftig die Diagnostik bei Fieber unklarer Genese oder nichtzuordenbaren Symptomenkomplexen zu erleichtern. In dem groß angelegten Projekt der Europäischen Union European Childhood Life-threatening Infectious Diseases Study (EUCLIDS) werden Blutproben von Kindern mit schweren Infektionserkrankungen gesammelt und mit den neuesten Methoden genetisch untersucht. Das Projekt stellt ein einzigartiges Unterfangen dar, das von einem interdisziplinären Team mit Experten in Infektiologie, Immunologie, Genetik, Bioinformatik, Mikrobiologie, Public Health und Vakzinologie etabliert wurde. Geplante Untersuchungen im Rahmen des Studienprojekts sind u. a. die molekulargenetische Detektion von Erregern, die nicht anhand der Routinediagnostik erfasst werden, die Identifikation von humanen Genen, die für den Verlauf der Meningokokkeninfektion verantwortlich sind, die Identifikation von humanen Suszeptibilitätsgenen bei Infektionen mit Pneumokokken, Staphylokokken und Gruppe-A-Streptokokken, Genexpressionsanalysen bei extremen Verlaufsformen dieser Infektionen sowie die Untersuchung von Impfantworten anhand genomweiter Assoziationsstudien.

Abstract

Modern molecular genetics now provide a realm of new methods for pinpointing genes or regions of interest causative for susceptibility and outcome of infectious diseases. Linkage analyses and twin studies have been applied for infectious diseases but so far only few traits have been successfully mapped to a gene locus. Genetic association studies may be an effective approach to the problem posed by complex traits. With the explosion of genotyping technologies, genome-wide association studies and full exome sequencing have become feasible. Gene expression analyses can detect the specific responses of the host and may lead to faster and more reliable diagnoses for fever without an obvious cause in children. A new European project funded by the 7th framework program, the European childhood life-threatening infectious diseases study (EUCLIDS) aims to use these methods to identify mechanisms underlying susceptibility, provide new targets for treatment and prevention and identify those at risk of disease or poor outcome. This is a unique European project, which has established an interdisciplinary team with expertise in infectious diseases, immunogenetics, bioinformatics, microbiology, public health and vaccinology. Within this project several sub-studies are planned, e.g. molecular genetic detection of pathogens that are not included in routine diagnostics, identification of human genes that are causally related to severity in meningococcal infections, identification of human susceptibility genes in other severe infections with Streptococcus pneumoniae, Staphylococcus and group A streptococci, gene expression profiling in extreme phenotypes and genetic investigations of vaccine responses.

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Danksagung

Dieses Forschungsprojekt wird durch das 7. Rahmenprogramm der Europäischen Union gefördert (EC-GA Nr. 279185; EUCLIDS).

Einhaltung ethischer Richtlinien

Interessenkonflikt. A. Binder, D.S. Klobassa, A. Sonnleitner, A. Trobisch, W. Zenz geben an, dass kein Interessenkonflikt besteht.

Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethikkommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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Authors and Affiliations

  1. Klinische Abteilung für Allgemeine Pädiatrie, Medizinische Universität Graz, Auenbruggerplatz 34/2, 8036, Graz, Österreich

    A. Binder, D.S. Klobassa, A. Trobisch &  W. Zenz

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  1. A. Binder
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  2. D.S. Klobassa
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  3. A. Trobisch
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  4. W. Zenz
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Correspondence to W. Zenz.

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Binder, A., Klobassa, D., Trobisch, A. et al. Genetische Untersuchungen an Kindern mit schweren bakteriellen Infektionserkrankungen. Monatsschr Kinderheilkd 163, 448–454 (2015). https://doi.org/10.1007/s00112-014-3250-2

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  • DOI: https://doi.org/10.1007/s00112-014-3250-2

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