Vision is the most developed of the human senses. Our eyes can be considered as the portal through which we gain knowledge, we communicate, as well as we appreciate all the beauty of the world.
The goal of this work is to better understand the molecular etiology underlying rare Mendelian cases of retinal degeneration and create knowledge about this disease’s mechanisms, in view of future developments of therapeutic interventions. In our approach, we couple the use of whole-genome, whole-exome, and RNA-sequencing, along with bench side basic research, in order to assess and better understand the functional
consequences that identified mutations elicit on normal molecular and physiological processes. From the beginning of this PhD, my training focused on bioinformatics and specifically on methods of analysis of next generation sequencing data. Provided that my background is that of a molecular biologist, I could in fact develop all my projects from A to Z, by performing in silico genomic data analysis and by implementing it into experimental research approaches.
The main results of my work consist in novel disease-gene associations, in particular for syndromic ciliopathies causing loss of vision and male infertility. In the projects on the TTLL5 and ARL2BP genes we link two structurally similar, yet functionally different, ciliary organelles - the photoreceptor sensory cilium and the sperm flagellum – associating vision and the reproductive system. Another novel disease-gene association is discussed in the third project, where we bring evidences for the contribution of a disruptive structural variant in the NMNAT1 gene to a rare, severe, and unique form of syndromic Leber congenital amaurosis. Finally, in the fourth project, we perform a whole-genome sequencing investigation of unresolved, negative exomes, and we identify new structural variants in the EYS and CNGA1 genes, as well as a large chromosomal rearrangement leading to uniparental isodysomy.