Characterization of autism spectrum disorder caused by alterations in complex genomic regions: molecular and pathophysiological mechanisms

• Autores: Mar Costa Roger
• Directores de la Tesis: L. A. Pérez Jurado (dir. tes.), Ivon Cusco Marti (codir. tes.)
• Lectura: En la Universitat Pompeu Fabra ( España ) en 2021
• Idioma: español
• Tribunal Calificador de la Tesis: Bru Cormand Rifa (presid.), Ferran Casals López (secret.), Marta Ribases Haro (voc.)
• Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
• Materias:
  • Ciencias de la vida
    • Biología humana
      • Genética humana
    • Biología vegetal (botánica)
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders, the etiology of which is unknown in the majority of cases. Little is known about complex genomic regions containing part of the missing heritability. In this thesis, we have assessed three complex genomic regions including the well-known 7q11.23 locus and unexplored 8p23.1 and 17q21.31 loci bearing common inversions. We have performed genomic and transcriptomic analyses to unravel common pathophysiological mechanisms in ASD patients with several susceptibility variants (Dup7, inv8p23.1 and inv17q21.31) and also in idiopathic patients considering a multiple-hit model. By using these strategies, we have uncovered several pathways and GO categories, including cholesterol biosynthesis, actin cytoskeletal dynamics, glutamate receptor signaling and immune-inflammatory pathways, that could partially contribute to the underlying molecular mechanism of ASD. Lastly, our data supports the implication of previously ASD-related genes and points out the potential role of novel ASD candidate genes such as NR4A3, SLC12A6 or DUSP6.