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 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.
Genome Analysis, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany.
Jeanette
J
Kirschner
David
D
Weber
Christina
C
Neuschl
Andre
A
Franke
Marco
M
Böttger
Lea
L
Zielke
Eileen
E
Powalsky
Marco
M
Groth
Dmitry
D
Shagin
Andreas
A
Petzold
Nils
N
Hartmann
Christoph
C
Englert
Gudrun A
GA
Brockmann
Matthias
M
Platzer
Alessandro
A
Cellerino
Kathrin
K
Reichwald
D000375:Aging; D000483:Alleles; D000818:Animals; D002875:Chromosomes / Q000235:genetics; D005260:Female; D005399:Fishes / Q000235:genetics*; D055106:Genome-Wide Association Study; D008297:Male; D008954:Models, Biological; D040641:Quantitative Trait Loci