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Identification of Candidate Genes and Physiological Pathways Involved in Gonad Deformation in Whitefish (Coregonus spp.) from Lake Thun, Switzerland
Computational and Molecular Populations Genetics Lab, University of Bern, Baltzerstrasse 6, 3012 Bern, Switzerland
Liverpool Microarray Facility, School of Biological Sciences, University of Liverpool, L69 7ZB Liverpool, UK
Centre for Fish and Wildlife Health, University of Bern, Laenggass-Strasse 122, PO-Box 8466, 3001 Bern, Switzerland
Institute of Clinical Chemistry, University Hospital, University of Bern, Inselspital, 3010 Bern, Switzerland
* Author to whom correspondence should be addressed.
Received: 28 April 2011; in revised form: 7 June 2011 / Accepted: 15 June 2011 / Published: 30 June 2011
Abstract: In 2000, fishermen reported the appearance of deformed reproductive organs in whitefish (Coregonus spp.) from Lake Thun, Switzerland. Despite intensive investigations, the causes of these abnormalities remain unknown. Using gene expression profiling, we sought to identify candidate genes and physiological processes possibly associated with the observed gonadal deformations, in order to gain insights into potential causes. Using in situ-synthesized oligonucleotide arrays, we compared the expression levels at 21,492 unique transcript probes in liver and head kidney tissue of male whitefish with deformed and normally developed gonads, respectively. The fish had been collected on spawning sites of two genetically distinct whitefish forms of Lake Thun. We contrasted the gene expression profiles of 56 individuals, i.e., 14 individuals of each phenotype and of each population. Gene-by-gene analysis revealed weak expression differences between normal and deformed fish, and only one gene, ictacalcin, was found to be up-regulated in head kidney tissue of deformed fish from both whitefish forms, However, this difference could not be confirmed with quantitative real-time qPCR. Enrichment analysis on the level of physiological processes revealed (i) the involvement of immune response genes in both tissues, particularly those linked to complement activation in the liver, (ii) proteolysis in the liver and (iii) GTPase activity and Ras protein signal transduction in the head kidney. In comparison with current literature, this gene expression pattern signals a chronic autoimmune disease in the testes. Based on the recent observations that gonad deformations are induced through feeding of zooplankton from Lake Thun we hypothesize that a xenobiotic accumulated in whitefish via the plankton triggering autoimmunity as the likely cause of gonad deformations. We propose several experimental strategies to verify or reject this hypothesis.
Keywords: oligonucleotide microarrays; gene expression; reproductive organ; gene expression profiling; autoimmunity; complement
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Bittner, D.; Cossins, A.R.; Segner, H.; Excoffier, L.; Largiadèr, C.R. Identification of Candidate Genes and Physiological Pathways Involved in Gonad Deformation in Whitefish (Coregonus spp.) from Lake Thun, Switzerland. Int. J. Environ. Res. Public Health 2011, 8, 2706-2733.
Bittner D, Cossins AR, Segner H, Excoffier L, Largiadèr CR. Identification of Candidate Genes and Physiological Pathways Involved in Gonad Deformation in Whitefish (Coregonus spp.) from Lake Thun, Switzerland. International Journal of Environmental Research and Public Health. 2011; 8(7):2706-2733.
Bittner, David; Cossins, Andrew R.; Segner, Helmut; Excoffier, Laurent; Largiadèr, Carlo R. 2011. "Identification of Candidate Genes and Physiological Pathways Involved in Gonad Deformation in Whitefish (Coregonus spp.) from Lake Thun, Switzerland." Int. J. Environ. Res. Public Health 8, no. 7: 2706-2733.