Mapping of quantitative trait loci controlling lifespan in the short‐lived fish Nothobranchius furzeri– a new vertebrate model for age research

• Published in: Aging cell Vol. 11; no. 2; pp. 252 - 261
• Main 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
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2012; John Wiley & Sons, Inc
• Subjects: Aging; Alleles; Animals; Chromosomes - genetics; Female; Fishes - genetics; genetic linkage map; Genome-Wide Association Study; lifespan; Male; Models, Biological; Nothobranchius; Nothobranchius furzeri; Original; Oryzias latipes; QTL mapping; Quantitative Trait Loci; synteny; Africa
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/j.1474-9726.2011.00780.x

Summary
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 F2 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 F2 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.