Quantitative trait loci, genes, and polymorphisms that regulate bone mineral density in mouse

Abstract

This is an in silico analysis of data available from genome-wide scans. Through analysis of QTL, genes and polymorphisms that regulate BMD, we identified 82 BMD QTL, 191 BMD-associated (BMDA) genes, and 83 genes containing known BMD-associated polymorphisms (BMDAP). The catalogue of all BMDA/BMDAP genes and relevant literatures are provided. In total, there are substantially more BMDA/BMDAP genes in regions of the genome where QTL have been identified than in non-QTL regions. Among 191 BMDA genes and 83 BMDAP genes, 133 and 58 are localized in QTL region, respectively. The difference was still noticeable for the chromosome distribution of these genes between QTL and non-QTL regions. These results have allowed us to generate an integrative profile of QTL, genes, polymorphisms that determine BMD. These data could facilitate more rapid and comprehensive identification of causal genes underlying the determination of BMD in mouse and provide new insights into how BMD is regulated in humans.

Microarray Analysis of Human Adipose-Derived Stem Cells in Three-Dimensional Collagen Culture: Osteogenesis Inhibits Bone Morphogenic Protein and Wnt Signaling Pathways, and Cyclic Tensile Strain Causes Upregulation of Proinflammatory Cytokine Regulators and Angiogenic Factors

“…6a). Two genes upregulated in response to 10% cyclic tensile strain during osteogenesis of hASC were also validated with RT-PCR: (1) PDLIM4, one of the top five upregulated genes that have been shown to have polymorphisms found to associate with bone mineral density regulation 23,24 ; (2) VEGF A, a known angiogenic factor. Real-time RT-PCR results confirmed that expression of both genes was significantly increased by hASC in response to 10% uniaxial cyclic tensile strain (Fig.…”

“…Of particular interest was the upregulation of PDLIM4, one of the top five upregulated genes that have been shown to have polymorphisms found to associate with bone mineral density regulation. 23,24 The addition of 10% uniaxial cyclic tensile strain also resulted in hASC upregulation of two crucial factors in bone regeneration: (1) proinflammatory cytokine regulators IL1RN and SOCS3; (2) angiogenic inductors FGF2, MMP2, and VEGF A.…”

Congenic mice provide in vivo evidence for a genetic locus that modulates intrinsic transforming growth factor β1–mediated signaling and bone acquisition

“…Quantitative trait locus (QTL) mapping is a powerful method for identifying genomic regions that harbor genes (quantitative trait loci, or QTLs) involved in shaping complex phenotypes, such as BMD (6,8). QTL analysis typically employs genetically heterogeneous populations derived from two or more highly inbred progenitor strains.…”

“…QTL analysis typically employs genetically heterogeneous populations derived from two or more highly inbred progenitor strains. Several investigators have used genome-wide linkage scans to search for QTLs associated with BMD in mice (reviewed in (5,6,8)), and several QTLs have been mapped to similar locations in the mouse genome in studies involving different murine strains (6,9), thus lending support to the validity of this experimental approach.…”

Genetics of osteoporosis: accelerating pace in gene identification and validation

“…Employment of this approach has mapped numerous QTLs for osteoporosis-related traits, particularly, BMD in mice Xiong et al 2009b) and, at the same time, provided many valuable insights into the complex genetic architecture of these traits (Zmuda et al 2006). However, to date, this approach has only contributed directly to the identiWcation of a very limited number of mouse BMD genes such as Alox15 (Klein et al 2004), Sfrp4 (Nakanishi et al 2006), Darc (Edderkaoui et al 2007) and Ece1 (Saless et al 2009).…”