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- W43354870 abstract "Recent advances in genomics and high-throughput technologies have significantly contributed to our understanding of spermatogenesis by identifying numerous genes expressed during the development of male gametes. These approaches do not, however, pinpoint the essential genes and several strategies can be adopted for the selection of candidate genes for functional genomic studies. The first part of this thesis describes a screen based on conserved and differential expression in the testis from three mammalian species. Homologs of candidate genes were inactivated in the C. Elegans model and worms were assayed for infertility phenotypes. The second part describes the construction of a tool for 'prioritizing' candidate genes based on phenotype and other data of relevance to the subject. We implemented a system capable of ranking genes for spermatogenesis based on multiple types of genomic information. The resulting Gene Prioritization System (GPSy) is currently the most comprehensive approach available and utilizes information available for some species to prioritize genes in a wide range of organisms. In the third part of the thesis, I applied this system to the set of candidate genes targeted by RNAi in the worm and demonstrate GPSy‘s ability to efficiently discriminate positive candidates from those showing no phenotype. I also tested the use of this tool in the mammalian context by prioritizing a list of genes identified by expression profiling of infertile patients. The justification of several high- and low-ranking genes, both in the human and the worm datasets, suggests that the system is scientifically sound and stresses the importance of a cross-species approach. Integrative genomics approaches, such as those presented in this manuscript, will play a decisive role in the identification of genes important for spermatogenesis and reproductive disorders." @default.
- W43354870 created "2016-06-24" @default.
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- W43354870 date "2011-01-01" @default.
- W43354870 modified "2023-09-24" @default.
- W43354870 title "Identifying genes important for mammalian spermatogenesis : a cross-species gene prioritization approach" @default.
- W43354870 hasPublicationYear "2011" @default.
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