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- Title
Mapping of quantitative trait loci controlling lifespan in the short-lived fish Nothobranchius furzeri--a new vertebrate model for age research.
- Authors
Kirschner, Jeanette; Weber, David; Neuschl, Christina; Franke, Andre; Böttger, Marco; Zielke, Lea; Powalsky, Eileen; Groth, Marco; Shagin, Dmitry; Petzold, Andreas; Hartmann, Nils; Englert, Christoph; Brockmann, Gudrun A; Platzer, Matthias; Cellerino, Alessandro; Reichwald, Kathrin
- Abstract
The African annual fish Nothobranchius furzeri emerged as a new model for age research over recent years. Nothobranchius furzeri show an exceptionally short lifespan, age-dependent cognitive/behavioral decline, expression of age-related biomarkers, and susceptibility to lifespan manipulation. In addition, laboratory strains differ largely in lifespan. Here, we set out to study the genetics of lifespan determination. We crossed a short- to a long-lived strain, recorded lifespan, and established polymorphic markers. On the basis of genotypes of 411 marker loci in 404 F(2) progeny, we built a genetic map comprising 355 markers at an average spacing of 5.5 cM, 22 linkage groups (LGs) and 1965 cM. By combining marker data with lifespan values, we identified one genome-wide highly significant quantitative trait locus (QTL) on LG 9 (P < 0.01), which explained 11.3% of the F(2) lifespan variance, and three suggestive QTLs on LG 11, 14, and 17. We characterized the highly significant QTL by synteny analysis, because a genome sequence of N. furzeri was not available. We located the syntenic region on medaka chromosome 5, identified candidate genes, and performed fine mapping, resulting in a c. 40% reduction of the initial 95% confidence interval. We show both that lifespan determination in N. furzeri is polygenic, and that candidate gene detection is easily feasible by cross-species analysis. Our work provides first results on the way to identify loci controlling lifespan in N. furzeri and illustrates the potential of this vertebrate species as a genetic model for age research.
- Publication
Aging cell, 2012, Vol 11, Issue 2, p252
- ISSN
1474-9726
- Publication type
Journal Article
- DOI
10.1111/j.1474-9726.2011.00780.x