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

The African annual fish Nothobranchius furzeri emerged as new model for age research over recent years. N. 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. Based on 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 1,965 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, defined candidate genes and performed fine mapping, resulting in a ∼40% reduction of the initial 95% confidence interval. We show that lifespan determination in N .furzeri is polygenic and 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 genetic model for age research.