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Every project supported by Gebert Rüf Stiftung is made accessible with a web presentation that informs about the core data of the project. With this public presentation, the foundation publishes the funding results achieved and contributes to the communication of science to society.

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Next Generation Sequencing and Functional Platform – Rare Diseases 2014

Editorial

Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.

Cooperation

This project is one of the five winners of the call 2014 «Rare Diseases - New Approaches». Project partners: Clinical Center, National Institutes of Health, Bethesda, MD, USA; Centre for Molecular Medicine, Department of Pediatric Medicine and Surgery, CHUV, Lausanne

Project data

  • Project no: GRS-061/14 
  • Amount of funding: CHF 250'000 
  • Approved: 06.11.2014 
  • Duration: 05.2015 - 01.2019 
  • Area of activity:  Rare Diseases, 2009 - 2014

Project management

Project description

Primary immunodeficiency diseases (PID) are a heterogeneous group of rare disorders that affect the immune system and cause an increased number of serious infections in affected individuals. Most patients affected with PID are identified in childhood, but an increasing number of conditions interfering with the normal function of the immune system are also discovered in adult individuals. About 300 forms of PID are currently known and while several conditions have easily recognizable clinical presentations, in many cases different diseases have overlapping and common clinical features. In addition, atypical presentations of well-known syndromes often complicate the clinical interpretation. Genetic analysis offers the possibility of establishing a definitive diagnosis, which is of paramount importance to make prognostic assessments and to provide patients and families adequate clinical management and genetic counseling. The objective of this project is, therefore, to establish a diagnostic platform that will allow to determine the genetic component that underlies the disease phenotype. A complementary objective of the project is to characterize the mechanisms of the immune systems that are affected by the genetic mutations, which will provide additional notions of how the immune system develops and works in health and disease.

What is special about the project?

This project has taken advantage of the recent revolution of genomic analysis brought about by the development of high-throughput, next generation sequencing (NGS) methods to perform screening of genes responsible for known forms of PIDs, as well as of candidate genomic regions that may be implicated in the pathophysiology of still undefined immunologic defects. Using cutting edge methods of molecular and cellular biology (e.g. CRISPR/Cas-9, iPS cells), this project is developing cellular models that recapitulate the immune defects observed in humans, which will inform the developments of new forms of therapies for PIDs.

Status/Results

We have identified 362 genes that are either known to be at the basis of or can be hypothesized to be associated with various forms of PIDs. A library of primers covering the coding sequences of such genes has been generated that results in around 5500 amplified sequences. After validation of the NGS platform using DNA samples from healthy control subjects and patients affected with known forms of PID, a series of 60 samples from pediatric and adult patients with clinical diagnosis of PID were then sequenced and analyzed. Such process resulted in the definition of 12 molecular diagnoses (20% of cases), as well as the identification of a potential new mechanism of a new autoinflammatory disease that is currently being modeled in the laboratory.

Publications

Droz-Georget S, Riccio O, Royer-Bertrand B, Superti-Furga A, Candotti F. [Next generation sequencing: a diagnostic tool for inherited immune defects]. Rev Med Suisse. 2017 Apr 5;13(557):763-766. French. PubMed PMID: 28722367.

Persons involved in the project

Fabio Candotti, Professeur Associé UNIL
Stéphanie Georget-Droz, PhD
Orbicia Riccio, PhD
Davide Mercuri, Administrative Manager

Last update to this project presentation  13.03.2019