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Genetic profiling of the peripheral nervous system
de Jonge, R.R.
Publication date
2003
Link to publication
Citation for published version (APA):
de Jonge, R. R. (2003). Genetic profiling of the peripheral nervous system.
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Summary 167
Conclusion
Several molecular strategies were applied to reveal genes involved in the origin andpathogenetic mechanisms of the hereditary neuropathies.
The first approach resulted in the identification of the NDGRI gene as the cause for HMSNL. In a second approach, construction of SAGE libraries and macroarray exper-iments generated a wealth of information, revealing several interesting genes and biological pathways that need further investigation. The major categories of genes highly expressed in peripheral nerve are involved in cell structure, developmental processes, lipid metabolism and protein biosynthesis. A novel observation is the high expression of genes of the complement system. The comparison of expression pro-files of Schwann cell cultures derived from patients and normal healthy controls has identified a small amount of interesting genes for future studies. Especially SEMA3C is a putative candidate for a key gene involved in the pathogenesis of HMSNL. Linkage of our macroarray results to disease loci showed t w o genes of particular interest, chaperonin containing t-complex polypeptide-1, subunit 6A (CCT6A), which is located in the HMSN2D region and cathepsin D (CSTD), which is located at the HMSN4B2 region. These genes might be good candidate genes for hereditary neuropathies. This analysis showed that SAGE can be performed as an hypothesis generating tool and the small defined macroarray can be used t o verify these SAGE results in a larger set of sam-ples. We conclude that the advances in molecular biology especially in the high-throughput gene expression technologies are capable of producing insight into complex and functional disease processes of the peripheral nerve, whose etiologies are due t o multiple genetic factors and their interplay with the environment.
