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Mapping and Phenotype information for this QTL, its variants and associated markersJ:227466An F2 intercross between the larger LG/J inbred strain and the smaller SM/J inbred strain was performed in search of genes affecting the variation in the number of fibers, their size, and proportion of type I fibers in the soleus muscle between to two phenotypically divergent strains. Because all fibers pass through the belly of mouse soleus, a single cross section provides an accurate estimate of muscle cells. A two fold difference in muscle mass was measured between the two strains. 122 F2 mice were genotyped at 160 SNP markers nearly, evenly distributed across the genome. Interval mapping analysis revealed significant QTL for CSA (cross sectional area) of type I and type IIA fibers on Chromosomes 1, 6, and 11. [Table 2. Build 37.2]QTL Mfq1, muscle fiber QTL 1, mapped to Chr 1 with a LOD=5.43-6.43 at peak location 109.4 Mb, mapping between flanking locations 68.6 Mb and 148.7 Mb. Mfq1 accounted for between 6.1 and 11.2 percent of the trait variance. The LG/J allele conferred a greater CSAI/CSAIIA in a recessive mode of inheritance.QTL Mfq2, muscle fiber QTL 2, mapped to Chr 6 with a LOD=5.16-6.16 at peak location 118.4 Mb, mapping between flanking locations 88.4 Mb and 144.9 Mb. Mfq2 accounted for between 9.5 and 11.7 percent of the trait variance. The LG/J allele conferred a greater CSAI/CSAIIA in an additive mode at this locus.QTL Mfq3, muscle fiber QTL 3, mapped to Chr 11 with a LOD=5.04-6.36 at peak location 27.8 Mb, mapping between flanking locations 11.1 Mb and 62.7 Mb. Mfq3 was attributed with between 8.9 and 10.1 percent of trait variance. The effect of Mfq3 appeared to be male specific. The LG/J allele conferred a greater CSAI/CSAIIA in an additive mode at this locus also.Suggestive QTL for the percentage of type I fibers were detected on Chromosomes 2, 3, and 4 with the SM/J allele increasing type I fiber percentage on Chrs 2 and 3 and the LG/J allele increasing on Chr 4. The position of the QTL affecting CSA of type IIA fibers and the percentage of type I fibers overlapped on Chr 2, however, different alleles conferred an increasing effect, LG/J and SM/J respectively. [Table 2.]J:251734Muscle fiber cross-sectional area (CSA) and proportion of different fiber types are important determinants of muscle function and overall metabolism. The authors aimed to map 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 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. The following phenotypes were assessed: muscle fiber number (type I and IIA) and percent of type I muscle fibers, CSA of type I and type IIA fibers. Muscle fiber traits were manually analyzed with ImageJ software.Mice were genotyped using a custom-designed SNP array that included 4,610 polymorphic SNPs that were approximately evenly distributed across the genome. The genome-wide association analysis was performed in the combined population of the F34 and recently published F2 intercrosses using the R package QTLRel and mapped to genome coordinates from GRCm38.p3.Genome-wide association analysis mapped four QTL affecting the properties of muscle fibers:QTL Mfq3 (muscle fiber QTL 3) maps to Chr 11: 28.0 31.5 Mb. The LG/J allele confers increased CSA of type I and type IIA fibers at Mfq3. Mfq3 was previously identified in an F2 intercross of the same parental strains (Carroll AM, et al., 2011). The current study fine maps the location to a narrower QTL interval. In both studies, Mfq3 exhibited male specificity in both type I and IIA fibers.QTL Mfq4 (muscle fiber QTL 4) maps to Chr 2: 158.8 - 162.5 Mb. The SM/J allele confers greater percentage of type I fibers at Mfq4.QTL Mfq5 (muscle fiber QTL 5) maps to Chr 3: 33.6 - 40.0 Mb. The SM/J allele confers increased CSA of type I and type IIA fibers at Mfq5.QTL Mfq6 (muscle fiber QTL 6) maps to Chr 4: 57.7 62.7 Mb. The LG/J allele confers greater percentage of type I fibers at Mfq6. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 10/29/2024 MGI 6.24 |
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