Genetically determined phenotype covariation networks control bone strength

Journal of Bone and Mineral Research

Volumn 25, Issue 7, 2010, Pages 1581-1593

  Jepsen, Karl J ^a   Courtland, Hayden William ^a   Nadeau, Joseph H ^b  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Biomechanics; Bone; Chromosome substitution strains; Growth; Morphology; Phenotypic covariation; QTL; Recombinant inbred mouse strains; Strength; Systems genetics

Indexed keywords

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; BONE MASS; BONE STRENGTH; BONE STRUCTURE; CHROMOSOME 12; CHROMOSOME 18; CHROMOSOME 19; CHROMOSOME 8; DIAPHYSIS; FEMALE; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; INBRED STRAIN; MALE; MOUSE; MOUSE STRAIN; NONHUMAN; PHENOTYPE; QUANTITATIVE TRAIT LOCUS;

ANIMALS; BONE AND BONES; BONE DENSITY; FEMALE; MICE; PHENOTYPE; QUANTITATIVE TRAIT LOCI;

EID: 77954697149     PISSN: 08840431     EISSN: None     Source Type: Journal    
DOI: 10.1002/jbmr.41     Document Type: Article

References (81)

1. Liu YJ, Shen H, Xiao P, et al. Molecular genetic studies of gene identification for osteoporosis: a 2004 update. J Bone Miner Res. 2006;21:1511-1535.
2. Ralston SH. Genetics of osteoporosis. Proc Nutr Soc. 2007;66:158-165.
3. Xiong Q, Han C, Beamer WG, Gu W. A close examination of genes within quantitative trait loci of bone mineral density in whole mouse genome. Crit Rev Eukaryot Gene Expr. 2008;18:323-343. (Pubitemid 351991363)
4. Chen Y, Shen H, Yang F, et al. Choice of study phenotype in osteoporosis genetic research. J Bone Miner Metab. 2009;27:121-126.
5. Ruff C, Holt B, Trinkaus E. Who's afraid of the big bad Wolff? "Wolff's law" and bone functional adaptation. Am J Phys Anthropol. 2006;129:484-498.
6. Smith RW, Walker RR. Femoral expansion in aging women: Implications for osteoporosis and fractures. Science 1964;145:156-157.
7. Jepsen KJ, Hu B, Tommasini SM, et al. Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility. Mamm Genome 2007;18:492-507. (Pubitemid 47360414)
8. Zebaze RM, Jones A, Knackstedt M, Maalouf G, Seeman E. Construction of the femoral neck during growth determines its strength in old age. J Bone Miner Res 2007;22:1055-1061. (Pubitemid 351339728)
9. Tommasini SM, Nasser P, Hu B, Jepsen KJ. Biological Co-adaptation of Morphological and Composition Traits Contributes to Mechanical Functionality and Skeletal Fragility. J Bone Miner Res 2008;23:236-246. (Pubitemid 351160037)
10. Jepsen KJ, Hu B, Tommasini SM, et al. Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains. Mamm Genome 2009;20:21-33.
11. Tommasini SM, Hu B, Nadeau JH, Jepsen KJ. Phenotypic integration among trabecular and cortical bone traits establishes mechanical functionality of inbred mouse vertebrae. J Bone Miner Res 2009;24:606-620.
12. Churchill GA. Recombinant inbred strain panels: a tool for systems genetics. Physiol Genomics 2007;31:174-175.
13. Rutherford SL. Bioessays From genotype to phenotype: buffering mechanisms and the storage of genetic information. 2000;22:1095-1105.
14. Rutherford SL, Lindquist S. Hsp90 as a capacitor for morphological evolution. Nature 1998;396:336-342.
15. Marder E, Goaillard JM. Variability, compensation and homeostasis in neuron and network function. Nat Rev Neurosci 2006;7:563-574. (Pubitemid 43995432)
16. Llamas B, Belanger S, Picard S, Deschepper CF. Cardiac mass and cardiomyocyte size are governed by different genetic loci on either autosomes or chromosome Y in recombinant inbred mice. Physiol Genomics 2007;31:176-182. (Pubitemid 350014395)
17. Millward CA, Burrage LC, Shao H, et al. Genetic factors for resistance to diet-induced obesity and associated metabolic traits on mouse chromosome 17. Mamm Genome 2009;20:71-82.
18. Yingling VR. A delay in pubertal onset affects the covariation of body weight, estradiol, and bone size. Calcif Tissue Int 2009;84:286-296.
19. Pandey N, Bhola S, Goldstone A, et al. Inter-individual variation in functionally adapted trait sets is established during post-natal growth and predictable based on bone robusticity. J Bone Miner Res Epub. 2009.
20. Olson EC, Miller RL. Morphological Integration. The University of Chicago Press, Ltd., Chicago: 1958.
21. Cheverud JM. Phenotypic, genetic, and environmental morphological integration in the cranium. Evolution 1982;36:499-516.
22. Cheverud JM. Developmental integration and the evolution of pleiotropy. American Zoologist 1996;36:44-50.
23. Wolf JB, Pomp D, Eisen EJ, Cheverud JM, Leamy LJ. The contribution of epistatic pleiotropy to the genetic architecture of covariation among polygenic traits in mice. Evol Dev 2006;8:468-476. (Pubitemid 44267807)
24. Yershov Y, Baldini TH, Villagomez S, et al. Bone strength and related traits in HcB/Dem recombinant congenic mice. J Bone Miner Res 2001;16:992-1003.
25. Li X, Masinde G, Gu W, Wergedal J, Mohan S, Baylink DJ. Genetic dissection of femur breaking strength in a large population (MRL/ MpJ x SJL/J) of F2 Mice: single QTL effects, epistasis, and pleiotropy. Genomics 2002;79:734-740. (Pubitemid 34499490)
26. Li R, Tsaih S-W, Shockley K, et al. Structural model analysis of multiple quantitative traits. PLoS Genetics 2006;2:1046-1057. (Pubitemid 44147409)
27. Nadeau JH, Singer JB, Matin A, Lander ES. Analysing complex genetic traits with chromosome substitution strains. Nat Genet 2000;24:221-225. (Pubitemid 30132188)
28. Belknap JK. Chromosome substitution strains: some quantitative considerations for genome scans and fine mapping. Mamm Genome 2003;14:723-732.
29. Shao H, Burrage L, Sinasac D, et al. Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. PNAS 2008;105:19910-19914.
30. Govoni KE, Donahue LR, Marden C, Mohan S. Complex genetic regulation of bone mineral density and insulin-like growth factor-I in C57BL/6J-Chr #A/J/NaJ chromosome substitution strains. Physiol Genomics 2008;35:159-164.
31. Singer JB, Hill AE, Burrage LC, et al. Genetic dissection of complex traits with chromosome substitution strains of mice. Science 2004;304:445-448.
32. Pearson OM. Activity, climate, and postcranial robusticity: implications for modern human origins and scenarios of adaptive change. Curr Anthropol 2000;41:569-607.
33. Grace JB. Structural Equation Modeling and Natural Systems. Cambridge University Press, Cambridge: 2006.
34. Courtland H-W, Nasser P, Goldstone AB, Spevak L, Boskey AL, Jepsen KJ. FTIRI microspectroscopy and micromechanical testing reveal intra-species variation in mouse bone mineral composition and matrix maturity. Calcif Tissue Int 2008;83:342-353.
35. Skedros JG, Dayton MR, Sybrowsky CL, Bloebaum RD, Bachus KN. The influence of collagen fiber orientation and other histocompositional characteristics on the mechanical properties of equine cortical bone. J Exp Biol 2006;209:3025-3042.
36. Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci 1984;304:509-518.
37. Jepsen KJ, Pennington DE, Lee YL, Warman M, Nadeau J. Bone brittleness varies with genetic background in A/J and C57BL/6J inbred mice. J Bone Miner Res 2001;16:1854-1862. (Pubitemid 32911492)
38. Manly KF, Cudmore RH Jr, Meer JM. Map Manager QTX, cross-platform software for genetic mapping. Mamm Genome 2001;12:930-932.
39. Haley CS, Knott SA. A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 1992;69:315-324.
40. Visscher PM, Thompson R, Haley CS. Confidence intervals in QTL mapping by bootstrapping. Genetics 1996;143:1013-1020. (Pubitemid 26001097)
41. Churchill GA, Doerge RW. Empirical threshold values for quantitative trait mapping. Genetics 1994;138:963-971. (Pubitemid 24337818)
42. Sampson SB, Higgins DC, Elliot RW, et al. An edited linkage map for the AXB and BXA recombinant inbred mouse strains. Mamm Genome 1998;9:688-694.
43. Garn S. The earlier gain and the later loss of cortical bone. Charles C Thomas, Springfield, IL: 1970.
44. Koller DL, Schriefer J, Sun Q, et al. Genetic effects for femoral biomechanics, structure, and density in C57BL/6J and C3H/HeJ inbred mouse strains. J Bone Miner Res 2003;18:1758-1765.
45. Volkman SK, Galecki AT, Burke DT, Miller RA, Goldstein SA. Quantitative trait loci that modulate femoral mechanical properties in a genetically heterogeneous mouse population. J Bone Miner Res 2004;19:1497-1505.
46. Lang DH, Sharkey NA, Mack HA, et al. Quantitative trait loci analysis of structural and material skeletal phenotypes in C57BL/6J and DBA/2 second-generation and recombinant inbred mice. J Bone Miner Res 2005;20:88-99.
47. Alam I, Sun Q, Liu L, et al. Whole-genome scan for linkage to bone strength and structure in inbred Fischer 344 and Lewis rats. J Bone Miner Res 2005;20:1589-1596.
48. Rubin CJ, Brandstrom H, Wright D, et al. Quantitative trait loci for BMD and bone strength in an intercross between domestic and wildtype chickens. J Bone Miner Res 2007;22:375-384.
49. Wolf JB, Leamy LJ, Routman EJ, Cheverud JM. Epistatic pleiotropy and the genetic architecture of covariation within early and late-developing skull trait complexes in mice. Genetics 2005;171:683-694.
50. Karasik D, Dupuis J, Cupples LA, et al. Bivariate linkage study of proximal hip geometry and body size indices: the Framingham study. Calcif Tissue Int 2007;81:162-173.
51. Norgard EA, Roseman CC, Fawcett GL, et al. Identification of quantitative trait loci affecting murine long bone length in a two-generation intercross of LG/J and SM/J Mice. J Bone Miner Res 2008;23:887-895.
52. Klingenberg CP, Leamy LJ, Cheverud JM. Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible. Genetics 2004;166:1909-1921.
53. Klingenberg CP, Mebus K, Auffray JC. Developmental integration in a complex morphological structure: how distinct are the modules in the mouse mandible? Evol Dev 2003;5:522-531.
54. Albright F, Smith PH, Richardson AM. Post-menopausal osteoporosis. Its clinical features. JAMA 1941;116:2465-2474.
55. Szulc P, Munoz F, Duboeuf F, Marchand F, Delmas PD. Low width of tubular bones is associated with increased risk of fragility fracture in elderly men - the MINOS study. Bone 2006;38:595-602.
56. Landin L, Nilsson BE. Bone mineral content in children with fractures. Clin Orthop Relat Res 1983;(178):292-296.
57. Milgrom C, Giladi M, Simkin A, et al. The area moment of inertia of the tibia: a risk factor for stress fractures. J Biomech 1989;22:1243-1248.
58. Crossley K, Bennell KL, Wrigley T, Oakes BW. Ground reaction forces, bone characteristics, and tibial stress fracture in male runners. Med Sci Sports Exerc 1999;31:1088-1093.
59. Bonnard G. Cortical thickness and diaphysial diameter of the metacarpal bones from the age of three months to eleven years. Helv Paediatr Acta 1968;23:445-463.
60. Klein RF, Turner RJ, Skinner LD, et al. Mapping quantitative trait loci that influence femoral cross-sectional area in mice. J Bone Miner Res 2002;17:1752-1760.
61. Volkman SK, Galecki AT, Burke DT, et al. Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population. J Bone Miner Res 2003;18:1497-1505.
62. Turner CH, Sun Q, Schriefer J, et al. Congenic mice reveal sex-specific genetic regulation of femoral structure and strength. Calcif Tissue Int 2003;73:297-303.
63. Drake TA, Hannani K, Kabo JM, Villa V, Krass K, Lusis AJ. Genetic loci influencing natural variations in femoral bone morphometry in mice. J Orthop Res 2001;19:511-517.
64. Wergedal JE, Ackert-Bicknell CL, Tsaih SW, et al. Femur mechanical properties in the F2 progeny of an NZB/B1NJ x RF/J cross are regulated predominantly by genetic loci that regulate bone geometry. J Bone Miner Res 2006;21:1256-1266.
65. Masinde GL, Wergedal J, Davidson H, et al. Quantitative trait loci for periosteal circumference (PC): identification of single loci and epistatic effects in F2 MRL/SJL mice. Bone 2003;32:554-560.
66. Miller LM, Little W, Schirmer A, Sheik F, Busa B, Judex S. Accretion of bone quantity and quality in the developing mouse skeleton. J Bone Miner Res 2007;22:1037-1045.
67. Jiao Y, Chiu H, Fan Z, et al. Quantitative trait loci that determine mouse tibial nanoindentation properties in an F2 population derived from C57BL/6J x C3H/HeJ. Calcif Tissue Int 2007;80:383-390.
68. Frost HM. Bone "mass" and the "mechanostat": a proposal. Anat Rec 1987;219:1-9.
69. Robling AG, Warden SJ, Shultz KL, Beamer WG, Turner CH. Genetic effects on bone mechanotransduction in congenic mice harboring bone size and strength quantitative trait loci. J Bone Miner Res 2007;22:984-991.
70. Mohan S, Masinde G, Li X, Baylink DJ. Mapping quantitative trait loci that influence serum insulin-like growth factor binding protein-5 levels in F2 mice (MRL/MpJ X SJL/J). Endocrinology 2003;144:3491-3496. (Pubitemid 36904427)
71. Gluer CC, Cummings SR, Pressman A, et al. Prediction of hip fractures from pelvic radiographs: the study of osteoporotic fractures. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 1994;9:671-677.
72. Kaptoge S, Beck TJ, Reeve J, et al. Prediction of incident hip fracture risk by femur geometry variables measured by hip structural analysis in the study of osteoporotic fractures. J Bone Miner Res 2008;23:1892-1904.
73. Duan Y, Beck TJ, Wang XF, Seeman E. Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res 2003;18:1766-1774. (Pubitemid 37322553)
74. Wang XF, Duan Y, Beck TJ, Seeman E. Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone 2005;36:978-986. (Pubitemid 40797998)
75. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002;359:1761-1767.
76. Christians JK, Senger LK. Fine mapping dissects pleiotropic growth quantitative trait locus into linked loci. Mamm Genome 2007;18:240-245.
77. Belknap JK, Mitchell SR, O'Toole LA, Helms ML, Crabbe JC. Type I and type II error rates for quantitative trait loci (QTL) mapping studies using recombinant inbred mouse strains. Behav Genet 1996;26:149-160.
78. Price CP, Herman BC, Lufkin T, Goldman HM, Jepsen KJ. Genetic variation in bone growth patterns defines adult mouse bone fragility. J Bone Miner Res 2005;20:1983-1991. (Pubitemid 41532784)
79. Yakar S, Canalis E, Sun H, et al. Serum IGF-1 determines skeletal strength by regulating sub-periosteal expansion and compensatory trait interactions. J Bone Miner Res 2009;24:1481-1492.
80. Kozloff KM, Carden A, Bergwitz C, et al. Brittle IV mouse model for osteogenesis imperfecta IV demonstrates postpubertal adaptations to improve whole bone strength. J Bone Miner Res 2004;19:614-622. (Pubitemid 41071222)
81. Wallace JM, Ron MS, Kohn DH. Short-term exercise in mice increases tibial post-yield mechanical properties while two weeks of latency following exercise increases tissue-level strength. Calcif Tissue Int 2009;84:297-304.