title: Fine-mapping of genes determining extrafusal fiber properties in murine soleus muscle.
abstract: 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. 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. Fiber number, CSA, and proportion of oxidative type I fibers were assessed in the soleus of 334 genotyped female and male mice of the F34generation 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 F2intercross of the same strains. Transcriptome of the soleus muscle of LG/J and SM/J females was analyzed by microarray. Genome-wide association analysis mapped four QTL (genome-wideP< 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 and 4.67 Mb. On the basis of the genomic sequence information and functional and transcriptome data, we identified candidate genes for each of these QTL. The combination of analyses in F2and F34AIL populations with transcriptome and genomic sequence data in the parental strains is an effective strategy for refining QTL and nomination of the candidate genes.
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill Aberdeen, United Kingdom.|The New Zealand Institute for Plant & Food Research Limited, Palmerston North, New Zealand.
authors.forename: A M
authors.initials: AM
authors.lastname: Carroll
authors.affiliation: Research School of Biology, Australian National University, Acton, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Cheng
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill Aberdeen, United Kingdom.|Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Old Aberdeen, Aberdeen, United Kingdom.
authors.forename: E S R
authors.initials: ES
authors.lastname: Collie-Duguid
authors.affiliation: Institute for Global Food Security, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Meharg
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill Aberdeen, United Kingdom.
authors.forename: M E
authors.initials: ME
authors.lastname: Scholz
authors.affiliation: Department of Microbiology/Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; and.
authors.forename: S
authors.initials: S
authors.lastname: Fiering
authors.affiliation: Department of Microbiology/Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; and.
authors.forename: J L
authors.initials: JL
authors.lastname: Fields
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California.
authors.forename: A A
authors.initials: AA
authors.lastname: Palmer
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill Aberdeen, United Kingdom; a.lionikas@abdn.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Lionikas
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D023281:Genomics; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010641:Phenotype; D020161:Physical Chromosome Mapping; D040641:Quantitative Trait Loci / Q000235:genetics; D012727:Sex Characteristics
keywords: genetic variation; muscle fiber types; skeletal muscle