Barth, Alexander: Identification of genetic factors involved in the regulation of stress. - Bonn, 2012. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc:
author = {{Alexander Barth}},
title = {Identification of genetic factors involved in the regulation of stress},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2012,
month = aug,

note = {In this QTL mapping study, several genetic regions were linked to anxiety- and depression-related behavior in the mouse. Furthermore, some previously identified QTL linked to these behavioral traits were verified in the present analysis, demonstrating the convergence of this approach and most previous studies. The novel QTL identified on chromosome 5 were narrowed to a common core interval of 9 cM. A subsequently applied comparative genomics approach with a syntenic region identified in a study in humans narrowed this core interval even more to a 15 Mb region. For the selection of possible candidate genes, a semantic similarity comparison of gene ontologies was conducted revealing three very prominent candidate genes, encoding for enolase phosphatase 1 (Enoph1) and 17·-hydroxysteroid dehydrogenases type 11 and 13 (Hsd17b11 and 13), respectively. These impressive results also demonstrated the power of gene ontology comparison on candidate gene prioritization.
All candidate genes revealed different expression levels in brain or liver between the parental strains, and for Enoph1, two non-synonymous co-segregating SNPs were verified in the parental strains, which is in line with recent publications. Further analysis confirmed differences in polyamines, which are regulated in anxiety and depression, but S-adenosylmethionine, the possible mediator of this result, revealed no variation. This leads to the conclusion that Enoph1 has no influence on S-adenosylmethionine levels and might have no influence on anxiety as well as depression by this mood enhancer.
Despite these results, Enoph1 still remains interesting as a candidate gene. It is possible that Enoph1 influences S-adenosylmethionine levels in the early postnatal phase and hence plays a role in epigenesis. The upcoming Enoph1 knockout mouse will provide deeper insights into the function of Enoph1. Upcoming research may resolve the question of what influence the genes Hsd17b11 and 13 have on steroid hormone regulation and anxiety as well as depression, since there are many unknown aspects. Taken together, all three candidate genes should be evaluated in further studies to identify the gene underlying the QTL. Additionally, future results of other QTL approaches with anxiety- and depression-related traits may provide the chance to narrow known QTL and simplify the selection of candidate genes.},

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