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Emergence of Cdh11 as a Primary Candidate Gene Regulating Femoral Morphology



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JBMR ORIGINAL ARTICLE Identification of Quantitative Trait Loci Influencing Skeletal Architecture in Mice Emergence of Cdh11 as a Primary Candidate Gene Regulating Femoral Morphology Charles R Farber 1 2 Scott A Kelly 3 Ethan Baruch 1 Daniel Yu 1 Kunjie Hua 3 Derrick L Nehrenberg 3 Fernando Pardo Manuel de Villena 3 Ryan J Buus 3 Theodore Garland Jr 4 and Daniel Pomp3 5 1 Center for Public Health Genomics University of Virginia Charlottesville VA USA Departments of Medicine and Biochemistry and Molecular Genetics University of Virginia Charlottesville VA USA 3 Department of Genetics and Carolina Center for Genome Science University of North Carolina Chapel Hill NC USA 4 Department of Biology University of California Riverside Riverside CA USA 5 Department of Nutrition Department of Cell and Molecular Physiology Carolina Center for Genome Science University of North Carolina Chapel Hill NC USA 2 ABSTRACT Bone strength is influenced by many properties intrinsic to bone including its mass geometry and mineralization To further advance our understanding of the genetic basis of bone strength related traits we used a large n 815 moderately G4 advanced intercross line AIL of mice derived from a high runner selection line HR and the C57BL 6J inbred strain In total 16 quantitative trait loci QTLs were identified that affected areal bone mineral density aBMD and femoral length and width Four significant p 05 and one suggestive p 10 QTLs were identified for three aBMD measurements total body vertebral and femoral A QTL on chromosome Chr 3 influenced all three aBMD measures whereas the other four QTLs were unique to a single measure A total of 10 significant and one suggestive QTLs were identified for femoral length FL and two measures of femoral width anteroposterior AP and mediolateral ML FL QTLs were distinct from loci affecting AP and ML width and of the 7 AP QTLs only three affected ML A QTL on Chr 8 that explained 7 1 and 4 0 of the variance in AP and ML respectively was



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