Skip to Main content Skip to Navigation

Exploration du rôle de l'épissage mineur dans le développement embryonnaire : modèle du syndrome de Taybi-Linder) (TALS)

Abstract : The Taybi-Linder Syndrome (TALS) is a rare genetic disorder of the embryonic development leading to a severe microcephaly, a primordial dwarfism and an early/unexpected death. The mutated gene in this syndrome is RNU4ATAC, which encode a non-coding small nuclear RNA (snRNA) named U4atac, involved in the minor spliceosome. This nuclear machinery is dedicated to the splicing of a small number of particular introns : the U12 introns. Because only about 1 % of the Human’s genes display at least one U12 intron, they have not been extensively study and little is known about their function. In TALS patients’ cells, most of the U12 introns are retained in mature transcripts ; hence, splicing of U12 introns seems important for the embryonic development. Studying TALS patients’ cells transcriptomes both in physiological and pathological conditions should enable us to precisely identify most of the molecular consequences of a minor splicing defect and could shed light on the mechanism linking minor splicing and embryonic development. This thesis is the first work to conduct an in depth analysis of TALS patients’ cells transcriptomes. In order to do a precise analysis, we developed a bioinformatic pipeline that uses multiple methods to detect differentially expressed or spliced genes between patients and controls and from second generation RNA-seq data. Splicing analysis is a very complex task complete with short reads ; hence, we used two complementary approaches. The first one is based on reads alignement to a reference genome, method conventionnally used to work on splicing, and the second one is based on reads assembly (KisSplice), a original method enabling to find more non-annotated splicing events. One of the expected consequences of a minor splicing malfunction is a global U12 introns retention in mature transcripts. However, intron retention detection and quantification in mammals is particulary difficult task in mammals, thus we used a new method dedicated to intron retentions analysis to study the transcriptomic profile of TALS patients. During my thesis, I was one of the developer of KisSplice and kissDE, our differential splicing analysis tool, and I identified important charcteristics of minor splicing either in physiological or pathological conditions
Document type :
Complete list of metadatas
Contributor : Abes Star :  Contact
Submitted on : Thursday, November 14, 2019 - 12:03:24 PM
Last modification on : Wednesday, November 20, 2019 - 1:30:30 AM
Long-term archiving on: : Saturday, February 15, 2020 - 2:08:18 PM


Version validated by the jury (STAR)


  • HAL Id : tel-02363211, version 1


Audric Cologne. Exploration du rôle de l'épissage mineur dans le développement embryonnaire : modèle du syndrome de Taybi-Linder) (TALS). Neurosciences. Université de Lyon, 2019. Français. ⟨NNT : 2019LYSE1190⟩. ⟨tel-02363211⟩



Record views


Files downloads