A narrow quantitative trait locus in C. elegans coordinately affects longevity, thermotolerance, and resistance to paraquat.

Authors: Vertino, Anthony; Ayyadevara, Srinivas; Thaden, John J; Shmookler Reis, Robert J

Abstract: By linkage mapping of quantitative trait loci, we previously identified at least 11 natural genetic variants that significantly modulate Caenorhabditis elegans life-span (LS), many of which would have eluded discovery by knock-down or mutation screens. A region on chromosome IV between markers stP13 and stP35 had striking effects on longevity in three inter-strain crosses (each P < 10(-9)). In order to define the limits of that interval, we have now constructed two independent lines by marker-based selection during 20 backcross generations, isolating the stP13-stP35 interval from strain Bergerac-BO in a CL2a background. These congenic lines differed significantly from CL2a in LS, assayed in two environments (each P < 0.001). We then screened for exchange of flanking markers to isolate recombinants that partition this region, because fine-mapping the boundaries for overlapping heteroallelic spans can greatly narrow the implicated interval. Recombinants carrying the CL2a allele at stP35 were consistently long-lived compared to those retaining the Bergerac-BO allele (P < 0.001), and more resistant to temperature elevation and paraquat (each approximately 1.7-fold, P < 0.0001), but gained little protection from ultraviolet or peroxide stresses. Two rounds of recombinant screening, followed by fine-mapping of break-points and survival testing, narrowed the interval to 0.18 Mb (13.35-13.53 Mb) containing 26 putative genes and six small-nuclear RNAs - a manageable number of targets for functional assessment.

Journal: Front Genet
Volume: 2
Pages: 63
Date: Feb. 4, 2012
PMID: 22303358
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Citation:

Vertino, Anthony, Ayyadevara, Srinivas, Thaden, John J, Shmookler Reis, Robert J (2012) A narrow quantitative trait locus in C. elegans coordinately affects longevity, thermotolerance, and resistance to paraquat. Front Genet 2: 63.


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