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Host genomics of extreme phenotypes caused by common viral diseases: genome sequencing in children with severe respiratory infections

English title Host genomics of extreme phenotypes caused by common viral diseases: genome sequencing in children with severe respiratory infections
Applicant Fellay Jacques
Number 133703
Funding scheme SNSF Professorships
Research institution Global Health Institute EPFL SV-DO
Institution of higher education EPF Lausanne - EPFL
Main discipline Genetics
Start/End 01.04.2011 - 31.03.2015
Approved amount 1'526'633.00
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All Disciplines (2)

Discipline
Genetics
Infectious Diseases

Keywords (4)

Human genomics; Infectious diseases; Sequencing; Pediatric respiratory infections

Lay Summary (English)

Lead
Lay summary

Host genetic studies seek to explain why individuals respond differently to infections. In recent years, major advances in genetic knowledge, bioinformatics and sequencing technology have transformed the field and allowed comprehensive studies of the human genome. This project proposes to use state-of-the-art genomic tools to look for genetic factors that predispose to severe viral respiratory infections in otherwise healthy children.

Although infections by respiratory viruses are usually mild and self-limited, severe symptoms develop in a small minority of children. This project postulates that rare mutations present in the genetic code of the patients are responsible for the most severe clinical presentations. Study participants will be recruited in Swiss pediatric intensive care units. During the course of the project, their genetic material (DNA and RNA) will be analyzed to obtain a complete genomic profile combining genome-wide genotyping, exome sequencing and RNA sequencing. Bioinformatic tools will be developed to handle very large amounts of data, to integrate the different layers of genomic information, and to identify the genetic factors that are likely to play a role in the severity of the disease.

The identification of genetic alterations conferring unusual susceptibility to respiratory infections has the potential to shed new light on the interactions between humans and viruses, and on the disease process. Consequently, the findings of this program could help develop novel diagnostic tools, preventive strategies and therapeutic interventions, and ultimately contribute to personalized medicine.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Adaptation on a genomic scale.
Bartha István, Fellay Jacques (2015), Adaptation on a genomic scale., in eLife, 4, 06193-06193.
Human genetic variation in HIV disease: beyond genome-wide association studies.
McLaren Paul J, Fellay Jacques (2015), Human genetic variation in HIV disease: beyond genome-wide association studies., in Current opinion in HIV and AIDS, 10(2), 110-5.
[Genomic medicine and infectious diseases].
Fellay Jacques (2014), [Genomic medicine and infectious diseases]., in Praxis, 103(10), 587-90.
Disentangling human tolerance and resistance against HIV.
Regoes Roland R, McLaren Paul J, Battegay Manuel, Bernasconi Enos, Calmy Alexandra, Günthard Huldrych F, Hoffmann Matthias, Rauch Andri, Telenti Amalio, Fellay Jacques, Swiss HIV Cohort Study (2014), Disentangling human tolerance and resistance against HIV., in PLoS biology, 12(9), 1001951-1001951.
A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
Bartha István, Carlson Jonathan M, Brumme Chanson J, McLaren Paul J, Brumme Zabrina L, John Mina, Haas David W, Martinez-Picado Javier, Dalmau Judith, López-Galíndez Cecilio, Casado Concepción, Rauch Andri, Günthard Huldrych F, Bernasconi Enos, Vernazza Pietro, Klimkait Thomas, Yerly Sabine, O'Brien Stephen J, Listgarten Jennifer, Pfeifer Nico, Lippert Christoph, Fusi Nicolo, Kutalik Zoltán, Allen Todd M, Müller Viktor (2013), A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control., in eLife, 2, 01123-01123.
European genetic diversity and susceptibility to pathogens.
McLaren Paul J, Fellay Jacques, Telenti Amalio (2013), European genetic diversity and susceptibility to pathogens., in Human heredity, 76(3-4), 187-93.

Collaboration

Group / person Country
Types of collaboration
Royal Children`s Hospital, Brisbane Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
Dominique Garcin, University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Mater Children`s Hospital, Brisbane Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ASHG annual meeting 2014 Poster Dissecting immune response to viral respiratory viruses using human genomics 13.10.2014 San Diego, United States of America Fellay Jacques; Hammer Christian; Bartha Istvan;
ASHG annual meeting 2013 Poster Exome sequencing in children with severe viral respiratory infections 24.10.2013 Boston, United States of America Thorball Christian Axel Wandall; Fellay Jacques; Bartha Istvan;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Connaissance 3 - le décodage du génome Western Switzerland 2014
Media relations: radio, television Corpus - séquençage du génome RTS1 Western Switzerland 2013
Media relations: print media, online media Ils traquent l'ADN des Suisses Le Matin Western Switzerland 2013
New media (web, blogs, podcasts, news feeds etc.) J Fellay - chercheur du mois GenSuisse German-speaking Switzerland Western Switzerland 2013
Media relations: print media, online media Le séquencage de l'ADN deviendra un test médical courant 24 Heures Western Switzerland 2013
Media relations: print media, online media L'ère de l'introspection génétique Le Temps Western Switzerland 2013
Media relations: print media, online media Mapping human resistance to HIV to find fighting-fit genetic helpers Wired International 2013
Media relations: radio, television Rencontre avec Jacques Fellay RTS1 Western Switzerland 2013

Associated projects

Number Title Start Funding scheme
133797 Biology Needs Ultra High Throughput DNA Sequencing 01.06.2011 R'EQUIP
153158 Swiss Pediatric Sepsis Study - a national prospective cohort study to assess epidemiology, novel immunodeficiencies and the impact of genetic variation on susceptibility to sepsis in children 01.07.2014 Project funding (special)
157529 Extreme Genomics: The influence of human genetic variation and pathogen sequence diversity on extreme phenotypes caused by viral infections 01.04.2015 SNSF Professorships

Abstract

My research seeks to better understand the impact of human genetic variation on infectious diseases. I here propose to test the hypothesis that severe manifestations of common viral respiratory infections in otherwise healthy children are due to rare genetic defects that can be identified by human genome and transcriptome sequencing. The identification of DNA variants, RNA expression profiles or splicing patterns conferring extreme susceptibility to viral respiratory infections could shed new light on host-pathogen interactions and on disease pathogenesis.
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