Mapping of quantitative trait loci controlling lifespan in the short-lived fish Nothobranchius furzeri- a new vertebrate model for age research
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 252-261 |
| Seitenumfang | 10 |
| Fachzeitschrift | Aging cell |
| Jahrgang | 11 |
| Ausgabenummer | 2 |
| Publikationsstatus | Veröffentlicht - Apr. 2012 |
| Peer-Review-Status | Ja |
| Extern publiziert | Ja |
Externe IDs
| PubMed | 22221414 |
|---|---|
| ORCID | /0000-0001-9599-8632/work/205331449 |
Schlagworte
ASJC Scopus Sachgebiete
Schlagwörter
- Genetic linkage map, Lifespan, Nothobranchius furzeri, QTL mapping, Synteny