title: Genetic Dissection of a QTL Affecting Bone Geometry.
abstract: Parameters of bone geometry such as width, length, and cross-sectional area are major determinants of bone strength. Although these traits are highly heritable, few genes influencing bone geometry have been identified. Here, we dissect a major quantitative trait locus (QTL) influencing femur size. This QTL was originally identified in an F2 cross between the C57BL/6J-hg/hg (HG) and CAST/EiJ strains and was referred to as femur length in high growth mice 2 (Feml2).Feml2was located on chromosome (Chr.) 9 at ∼20 cM. Here, we show that the HG.CAST-(D9Mit249-D9Mit133)/Ucd congenic strain capturesFeml2In an F2 congenic cross, we fine-mapped the location ofFeml2to an ∼6 Mbp region extending from 57.3 to 63.3 Mbp on Chr. 9. We have identified candidates by mining the complete genome sequence of CAST/EiJ and through allele-specific expression (ASE) analysis of growth plates in C57BL/6J × CAST/EiJ F1 hybrids. Interestingly, we also find that the refined location ofFeml2overlaps a cluster of six independent genome-wide associations for human height. This work provides the foundation for the identification of novel genes affecting bone geometry.
authors.affiliation: Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, Virginia 22908.|Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia 22908.
authors.forename: Olivia L
authors.identifier: 0000-0003-2334-5936
authors.initials: OL
authors.lastname: Sabik
authors.affiliation: Department of Animal Science, University of California, Davis, California 95616.
authors.forename: Juan F
authors.identifier: 0000-0001-7113-3183
authors.initials: JF
authors.lastname: Medrano
authors.affiliation: Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, Virginia 22908 crf2s@virginia.edu.|Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia 22908.|Department of Public Health Science, School of Medicine, University of Virginia, Charlottesville, Virginia 22908.
authors.forename: Charles R
authors.identifier: 0000-0002-6748-4711
authors.initials: CR
authors.lastname: Farber
mesh_terms: D000483:Alleles; D000818:Animals; D001827:Body Height / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D005269:Femur / Q000033:anatomy & histology*; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D008297:Male; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
keywords: QTL fine-mapping; allele-specific expression (ASE); bone geometry; bone strength; quantitative trait loci (QTL)