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Quantitative trait loci for exercise training responses in FVB/NJ and C57BL/6J mice.

ABSTRACT: The genetic factors determining the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with adaptation to exercise training in a cross between FVB/NJ (FVB) and C57BL/6J (B6) mice. Mice completed an exercise performance test before and after a 4-wk treadmill running program, and changes in exercise capacity, expressed as work (kg.m), were calculated. Changes in work in F(2) mice averaged 1.51 +/- 0.08 kg.m (94.3 +/- 7.3%), with a range of -1.67 to +4.55 kg.m. All F(2) mice (n = 188) were genotyped at 20-cM intervals with 103 single nucleotide polymorphisms (SNPs), and genomewide linkage scans were performed for pretraining, posttraining, and change in work. Significant QTL for pretraining work were located on chromosomes 14 at 4.0 cM [3.72 logarithm of odds (LOD)] and 19 at 34.4 cM (3.63 LOD). For posttraining work significant QTL were located on chromosomes 3 at 60 cM (4.66 LOD) and 14 at 26 cM (4.99 LOD). Suggestive QTL for changes in work were found on chromosomes 11 at 44.6 cM (2.30 LOD) and 14 at 36 cM (2.25 LOD). When pretraining work was used as a covariate, a potential QTL for change in work was identified on chromosome 6 at 68 cM (3.56 LOD). These data indicate that one or more QTL determine exercise capacity and training responses in mice. Furthermore, these data suggest that the genes that determine pretraining work and training responses may differ.

SUBMITTER: Massett MP

PROVIDER: S-EPMC2807210 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Quantitative trait loci for exercise training responses in FVB/NJ and C57BL/6J mice.

Massett Michael P MP Fan Ruzong R Berk Bradford C BC

Physiological genomics 20090929 1

The genetic factors determining the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with adaptation to exercise training in a cross between FVB/NJ (FVB) and C57BL/6J (B6) mice. Mice completed an exercise performance test before and after a 4-wk treadmill running program, and changes in exercise capacity, expressed as work (kg.m), were calculated. Changes in work in F(2) mice averaged 1.51 +/- 0.0 ...[more]

PMID: 19789284

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Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the âbiological signatureâ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Pairs of Cy5 and Cy3 labeled targets were co-hybridized onto either a custom long oligonucleotide microarray for the interrogation of 231 genes encompassed by QTL1 and QTL2, or a TIGR rat cDNA array consisting of 26,401 probe elements representing 20,465 unique non-QTL genes. A âflip-dyeâ or âbalanced blockâ design was used as the experimental method of choice to account for potential dye-bias labeling effects. Six âbalanced blockâ normalized files are submitted for the long oligonucleotide array interrogating the hearts from S versus S.LEW(5)x6x9 animals, fourteen âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x9 animals, and twelve âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x11 animals. GPR and MEV files cannot be located.

Dataset Information

Quantitative trait loci for exercise training responses in FVB/NJ and C57BL/6J mice.

Publications

Quantitative trait loci for exercise training responses in FVB/NJ and C57BL/6J mice.

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