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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jeanette Kirschner - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • David Weber - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Christina Neuschl - , Humboldt University of Berlin (Author)
  • Andre Franke - , Kiel University (Author)
  • Marco Böttger - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Lea Zielke - , Humboldt University of Berlin (Author)
  • Eileen Powalsky - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Marco Groth - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Dmitry Shagin - , Evrogen, Russian Academy of Sciences (Author)
  • Andreas Petzold - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Nils Hartmann - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Christoph Englert - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Gudrun A. Brockmann - , Humboldt University of Berlin (Author)
  • Matthias Platzer - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)
  • Alessandro Cellerino - , Leibniz Institute on Aging - Fritz Lipmann Institute, Scuola Normale Superiore di Pisa (Author)
  • Kathrin Reichwald - , Leibniz Institute on Aging - Fritz Lipmann Institute (Author)

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 5.5cM, 22 linkage groups (LGs) and 1965cM. By combining marker data with lifespan values, we identified one genome-wide highly significant quantitative trait locus (QTL) on LG9 (P<0.01), which explained 11.3% of the F 2 lifespan variance, and three suggestive QTLs on LG11, 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.

Details

Original languageEnglish
Pages (from-to)252-261
Number of pages10
JournalAging cell
Volume11
Issue number2
Publication statusPublished - Apr 2012
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 22221414
ORCID /0000-0001-9599-8632/work/205331449

Keywords

ASJC Scopus subject areas

Keywords

  • Genetic linkage map, Lifespan, Nothobranchius furzeri, QTL mapping, Synteny