Quantitative trait loci for bone density in mice: the genes determining total skeletal density and femur density show little overlap in F2 mice.
Bone mineral density variation is a highly heritable trait and is the best predictor of skeletal fragility. Total skeletal density was determined by PIXIMUS, and femur density was determined by pQCT. The data were analyzed for quantitative trait loci (QTL) to determine if bone density at a specific skeletal site (femur) would identify new gene loci or the same gene loci as total body (PIXIMUS). In order to show concordance and differences in QTL for total body bone density versus femur bone density, we performed a genome-wide scan from 633 (MRL x SJL) F2 mice. The bone mineral density (BMD) data from pQCT were used to identify nine QTL on chromosomes 1, 3, 4, 9, 12, 17, and 18, while nine QTL on chromosomes 1, 2, 4, 9, 11, 14, and 15 were identified by PIXIMUSdata, accounting for 32.5% and 30.4% variation in F2 mice, respectively. QTL on chromosomes 1, 2, 3, 9, 11, 12, 14, 15, 17, and 18 are unique to our study, as they have never been described before. Chromosome 1 (D1Mit33 and D1Mit362) had similar QTL between pQCT and PIXIMUS. Several QTL were identified for both femur and total body BMD but only two QTL were common for both of these phenotypes. This suggests that genes regulating bone density differ depending on the skeletal site analyzed.
Molecular Genetics Division, Musculoskeletal Disease Center, JL Pettis VA Medical Center and Loma Linda University, 11201 Benton street, Loma Linda, CA 92357, USA.
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Masinde
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Li
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Gu
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Wergedal
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Mohan
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Baylink
D000818:Animals; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D002874:Chromosome Mapping; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D018507:Gene Expression Regulation, Developmental; D005807:Genes, Overlapping; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D011859:Radiography