Genomics of immune disease. Exploring the genetic mechanisms underlying primary immunodeficiencies
- Autores: Laura Batlle Masó
- Directores de la Tesis: Tomàs Marques-Bonet (dir. tes.), Ferran Casals López (codir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2021
- Idioma: inglés
- Tribunal Calificador de la Tesis: Laia Alsina Manrique de Lara (presid.), Lara Nonell Mazelon (secret.), Ivon Cusco Marti (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
The human genome has been screened for variants causing disease ever since sequencing technologies appeared. Human diseases are diverse, and so are their causes. Therefore, finding the genetic cause underlying diseases in inherited disorders is not a straightforward task.
The main goal of this thesis is to explore the different genetic mechanisms causing immune disorders, namely autoinflammatory disease and hemophagocytic lymphohistiocytosis. For that, we combined the use of next-generation sequencing technologies and bioinformatic analysis, the results of which were evaluated in clinical discussions.
We found different causal genetic mechanisms in immunodeficient patients. We described monogenic alterations and somatic variants, as well as digenic combinations of genetic variants. We also explored the possibility of variant accumulation in known functional pathways. Finally, taking advantage of the data generated, we also evaluated the use of targeted sequencing and exome sequencing in clinical practice and discussed its suitability.
Overall, our results highlight that genetic analysis is a valuable diagnostic tool in patients with immune disorders. This is especially relevant in previously undiagnosed cases in which reaching a molecular diagnosis have direct clinical implications.
