Introduction. Muscle fiber cross-sectional area (CSA) and proportion of different fiber types are important determinants of muscle function and overall metabolism. Genetic variation plays a substantial role in phenotypic variation of these traits, however, the underlying genes remain poorly understood. Aims. This study aimed to map quantitative trait loci (QTL) affecting differences in soleus muscle fiber traits between the LG/J and SM/J mouse strains. Methods. Fiber number, CSA, and proportion of oxidative type I fibers were assessed in the soleus of 334 genotyped male and female mice of the F34 generation of advanced intercross lines (AIL) derived from the LG/J and SM/J strains. To increase the QTL detection power, these data were combined with 94 soleus samples from the F2 intercross of the same strains. Transcriptome of the soleus muscle of LG/J and SM/J females was analysed using microarray. Results. Genome-wide association analysis mapped 4 QTL (genome-wide p<0.05) affecting the properties of muscle fibers to Chromosome 2, 3, 4 and 11. A 1.5-LOD QTL support interval ranged between 2.36 Mb and 4.67 Mb. Based on the genomic sequence information, functional and transcriptome data, candidate genes were identified for each of these QTL. Conclusion. Combination of analyses in F2 and F34 AIL populations with transcriptome and genomic sequence data in the parental strains is an effective strategy for refining QTL and nomination of the candidate genes.
|Number of pages||10|
|Early online date||13 Jan 2017|
|Publication status||Published - 1 Mar 2017|
- skeletal muscle
- muscle fiber types
- genetic variation
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- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, MRC/Versus Arthritis Centre for Musculoskeletal Health and Work
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Senior Lecturer
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Centre for Arthritis and Musculoskeletal Health (ACAMH)